I have heard from colleagues in the alcohol field who fear hat any change will hurt their research. We heard very similar cries when NIH moved RO1 reviews from the institutes to CSR, but the predicted dire outcomes did not develop, and NIAAA/NIDA grants are fairly reviewed by CSR. Similarly, it seems likely that the best drug abuse work will be supported by a new addiction institute.

Lastly, treatment development - especially psychosocial treatment development for tobacco use will be important in the future. While there has been innovation in pharmacotherapy for smoking cessation in the last 20 years, there has been little innovation in psychosocial smoking cessation treatments.

Understanding the implications of policy changes on substance use patterns and trajectories, especially in youth, is vital to the development of effective evidence based policies rather than ideology based policies. Current public policy sentiment focuses so heavily on the legal status of alcohol and other drugs that it pushes people to the margins and we lose the opportunity to keep them connected in ways that address the core issues. E.g. is the problem "underage drinking" or is it "problematic drinking" or drinking before people are cognitively and socially able to use in moderate or healthier ways? I believe it is the latter.

Alleviating the translational bottleneck for treatments to move from the bench to the bedside to the community: Would it be possible to encourage pharmaceutical companies to partner with academic institutions in drug development for addictions by granting them extended proprietary periods, so that they might be more willing to conduct trials with academic instituions in addictions such as cocaine, amphetamine and methamphetamine?

The consequences of IPV are enormous. Direct medical and mental health services for female victims of IPV exceeded $5.8 billion annually as reported in 1995. IPV results in devastating consequences, including acute and chronic physical and mental health problems, divorce, suicide, and even spousal homicide. In an effort to better understand IPV, numerous studies have been conducted on risk factors for perpetration and victimization.

Substance use and abuse have been found to be consistent correlates of IPV perpetration and victimization in women and men. In men, a relationship between drinking and IPV has been established such that men in alcohol treatment programs are 11 times more likely to be physically violent towards female partners on drinking days relative to non-drinking days. Similarly, women in treatment for alcohol use are approximately 4 times more likely to perpetrate physical or sexual IPV on heavy drinking days relative to non-drinking days. In terms of victimization, male and female alcoholics were approximately 3 times more likely to be victims of physical IPV on drinking days, relative to non-drinking days. Similarly, other drugs, particularly cocaine use, are temporally associated with increased risk of violence perpetration and victimization.

There will be no benefit from this merger, just changes, additional costs, and confusion.

Critical Issues: It seems that a better organized, more systematic approach could be implemented to manage the various groups working to develop vaccines for drugs of abuse.

1. Many of the studies performed to develop vaccines for drugs of abuse are performed using a single vaccine candidate making it difficult/impossible to determine the potency of that candidate vaccine relative to another candidate vaccine. It may be helpful to scientists and the public if NIH would use a contract mechanism to develop a central laboratory that would test vaccine candidates for a particular drug of abuse in parallel to begin to build a database that would rank the immunogenicities/efficacies of the vaccine candidates.

The burden to the health care system, public health system, and to families and individuals of recurren relapses is well documented. We need to realize that continuing care goes beyond the care provided by intensive programs and addiciton specialists.

For example, our research group has devoted the past 15 years to studies of how chronic alcohol ingestion renders the lung susceptible to infections and injury. As a practicing pulmonary & critical care investigator as well as a biomedical researcher, I am keenly aware that there are enormous health consequences of alcohol use on vital organs (lung, heart, etc.)for which we must find effective therapies. If a 29 y/o with a history of heavy alcohol use dies of pneumonia or acute lung injury in the intensive care unit after a prolonged illness, they will never have the chance to attend addiction therapy. Each year in the U.S. hundreds of thousands of individuals die of alcohol- and drug-related illnesses and biomedical investigators from many disciplines are working to define the pathophysiology of these illnesses and to develop novel therapies.

To focus only on addiction would be akin to directing all resources for common illnesses such as type II diabetes and lung cancer to weight loss and smoking cessation programs only. Although in a 'perfect world' that might work, we all know that would not only be naive but would be an abdication of our responsibilities. In fact, we must develop better therapies for drug and alcohol addiciton in parallel with research that defines the biomedical consequences and that identifies novel therapies.

If the NIH essentially merges NIAAA and NIDA and this new institute focuses exclusively on funding studies on addiction, a valuable cadre of biomedical investigators will have no advocates at NIH and their research activity will be sharply curtailed if not ended. If NIH does proceed with this merger then it must allocate resources and promote support for this important research to the other institutes. I just know that every time I submit a research proposal on alcohol and lung biology, it is automatically referred to NIAAA for funding consideration. NHLBI has not developed any interest in this research because they have deferred to NIAAA. What will happen to investigators studying alcohol and the liver, alcohol and the lung etc. if NIAAA's role in supporting this research is suddenly eliminated?

Together, these areas address the effectiveness (and cost effectiveness) of programming for substance use or other addictive behaviors, the “key ingredients” of programming, adequacy of access, and success at retention in care. These are important healthcare questions with direct bearing for public health. Following the proposed reorganization, the new Institute will be uniquely positioned to support scientific inquiry into the specialized delivery system for substance use programs – a system that will bear much responsibility for translating new interventions and medications developed through Institute funding.

I believe these are critical issues because their elucidation can contribute to a basic and incremental science of understanding not only drug abuse but the mechanisms that lead to it, which will foster incremental and progressive science, by which NIDA and NIAAA have previously made such great strides.

Most pressing are their ability to critically think.

The addiction field has been plaged with poor thinking. Time to set out recommendations for those who assess and select treatments for clients.

2. Encouraging patient recognition and utilization of effective substance abuse treatments;

3. Encouraging research on the generation of novel metabolites resulting from the in situ interaction of alcohol with opiates, stimulants, hallucinogens, or inhalants (e.g., the production of cocaethylene when alcohol and cocaine are co-ingested) and their pharmacokinetic and pharmacodynamic properties and toxicity;

4. Alleviating the translational bottleneck for treatments to move from the bench to the bedside to the community;

5. Encouraging research to elucidate the impact of using one substance (e.g., alcohol) on likelihood of relapse to other substances (e.g., other drugs);

6. Understanding the mechanisms by which alcohol and other drugs of abuse increase risk for certain diseases (e.g. cancers), particularly when used in combination.

The reason is that humans are a unique but diverse species.

Type II translational research needs more explicit attention. We have so many programs that have proven to be effective and save money in the long run but we have yet to figure out how to get these programs disseminated widely. Gains in this area can have tremendous public health benefit.

Relatedly, the institute needs to support research on how to effectively promote policy change that can reduce substance use.

Science can contribute substantially to the prevention of substance use if it can improve our understanding of these complex but critical elements of effective substance use control.

Because referrals to 12-step programs have become ubiquitous in addiction treatment, despite very few studies on the spiritual mechanisms of action involved, further studies in spirituality and addiction are necessary to support existing treatment and develop more effective assessment and treatments.

This is of concern given the DSM-V proposal to broaden addiction to Behavioral and Substance Addictions, specifically including Pathological Gambling with Addictions. The AMA has highlighted the growing problem of Behavioral Addictions including Internet Gaming. Prevalence studies demonstrate very high rates for behavioral addictions. Public policy decisions to increase the development of Casino's contibute to the growth of the problem. If the proposed National Institute of Substance Use and Addiction Disorders fails to address this deficiency, then what Institute will take on this responsibility?

The extremely high co-morbidity between drug and alcohol abuse and psychiatric illness - this is critical for the public since there are data showing that more than 50% of all cigarettes are consumed by individuals with mental illness, and there is high co-morbidity between addiction disorders and mental illness, in general. This is important for scientists because currently, there is no mandate to take on the issue of co-morbidity in a single institute. These projects are often not funded by the NIMH because they are thought to be in the realm of NIDA or NIAAA. The new institute would be an excellent "home" for scientific studies of co-morbidity between substance use and mental illness.

The neurobiological and behavioral overlap in brain mechanisms governing food intake/obesity and drugs/alcohol

This is a critical issue for the public because of the rising obesity epidemic, and the clear dissociation between caloric need and food intake. The similarities and differences between drug addiction and food addiction are becoming a very important area for the development of novel therapeutics. This is an important area for scientists, because new tools are unraveling the neurobiological underpinnings of these disorders, but there is again, no scientific home for this type of study. NIDDK is more interested in studies of metabolic systems and obesity, whereas NIDA is focused on abuse of licit and illicit substances rather than food. An "addictions" Institute would be the ideal home for this type of research.

The role of drugs of abuse in inducing risk-taking behaviors as a predisposition to HIV infection

This is important for the public because the primary role that drug addiction plays in the spread and severity of HIV has been clear for years, but the role that brain changes following exposure to drugs of abuse plays in the increased risky behaviors, such as unprotected male-male sex, in the spread of HIV is less recognized. This is important to scientists because the study of the behavioral basis for HIV transmission is not appropriate for the NIAID and therefore should find a home in the new addictions Institute.

See: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm?s_cid=mm6106a1_w

While there may be downsides to the integrated institute, one advantage may be greater interest in developing cross-substance prevention and intervention efforts.

An additional priority is development of approaches that are easily scaled upward and relatively low-cost (even if effect sizes are smaller)--in the current institutional and budget climate, it is hard to imagine that time-and-money intensive programs would be possible to deploy in a large-scale way.

Unlike previous epidemics such as the dramatic surges in crack cocaine use of the 1980's and methamphetamine use in the late 1990's and early 2000's, NIH should be proactive in their sponsorship of research on newer drugs of abuse, from prevention, education, and basic and clinical research perspectives.

In other words, don't wait until these drugs create an new epidemic! Active research into this area could avert such a crisis.

Unlike previous epidemics such as the dramatic surges in crack cocaine use of the 1980's and methamphetamine use in the late 1990's and early 2000's, NIH should be proactive in their sponsorship of research on newer drugs of abuse, from prevention, education, and basic and clinical research perspectives.

In other words, don't wait until these drugs create an new epidemic! Active research into this area could avert such a crisis.

Please provide more opportunities for research for addiction treatment, prevention of use, and also health effects. Smoking and tobacco use effect users in multiple ways and more research has to be done to help users quit smoking in mulitiple ways.

1. Where opportunities list alcohol separate from other drugs, include tobacco: tobacco, alcohol, and other drugs

2. Early detection, intervention, and motivating people with drug abuse/dependence to try to quit is a huge problem. There should be an opportunity that explicitly includes this as a research focus, especially for marijuana dependence but also for other drugs. For example, only 20% of tobacco smokers are ready to set a quit date. 2a. In terms of early intervention, the Institute could include reducing the decades-long gap between addiction onset and cessation as an explicit goal.

3. Include an opportunity on research and practice to understand the co-occurance of mental health and addiction disorders, and to identify effective treatment of co-occuring disorders

3a. It would be great if the Institute could develop strong links with NIMH.

4. Type II translational research should be targeted - there should be an opportunity targeting dissemination and implementation research to enhance widespread adoption of effective interventions

5. Because tobacco is the #1 cause of lung cancer (not to mention all of the other cancers it contributes to) and lung cancer is the #1 cancer killer, it is extremely important for the institute to maintain strong links to the NCI and for the NCI to count tobacco projects funded by this new institute as cancer-related research.

2) Promoting early detection and intervention is extremely important because it is poorly addressed so far.

3) Untreated mental illnesses are major causes of abuse onset and relapse, but they are poorly addressed in research and not addressed at all in most treatment settings.

Tobacco use continues to be a major health issue and thus understanding the relationships between tobacco use, addiction, and psychiatric disorders is critically important.

Use of alcohol, not necessarily at levels of abuse, increases the incidence of cancer. The impact of alcohol in increasing the risk of cancer is largely unknown and the statistics are woefully out of date. Much of the research in this area is not being conducted in the United States because of a low priority that has been placed on this area. The most recent statistics from 2002, which are ten years out of date suggests that 3.6% of cancer are attributable to alcohol. At that time the connection between alcohol use and cancer was largely confined to heavy users; however, we now know that low levels of alcohol can also exhibit a carcinogenic effect (i.e. breast cancer). Thus, the incidence is likely much greater. While the knowledge of alcohol as an independent factor in causation of cancer is currently escalating, little is known regarding how continued alcohol use impacts cancer progression (invasion and metastasis) and survival of patients with cancer. The role of the immune response in cancer survival and metastasis has recently re-emerged as an important area for research, and alcohol is largely known to be immunosuppressive. Thus, alcohol could have a major impact in progression of cancer. These are important and emerging areas, in which more research is desperately needed. The impact of cancer on human health is immense given the volume of people with cancer and in addition those who have survived cancer. The effect of alcohol consumption on re-occurrence of cancer is also is an important and underexplored area of research. Before the merger discussions NIAAA intended to increase research on alcohol and cancer through an RFA process. Emphasis in this area is currently stalled pending decisions on the merger.

Drugs of abuse are also linked to cancer. For example, tobacco is well known to be carcinogenic, marijuana use is linked to testicular cancer, and liver cancer from use of anabolic steroids. The influence of alcohol in combination with drugs of abuse requires further investigation. To date most is known about the alcohol and tobacco connection; however again, very little is known regarding the impact of combination alcohol and drug abuse on cancer progression and survival.

Researchers in this area currently comprise a small group. Thus, we do not have a lot of lobbying clout. Therefore, I urge you to consider this area based on need for more research not upon the magnitude of the input that you receive.

Shannahoff-Khalsa D, An Introduction to Kundalini Yoga Meditation Techniques that are Specific for the Treatment of Psychiatric Disorders, The Journal of Alternative and Complementary Medicine, 10(1), 91-101, 2004.

This technique is also published in the following encyclopedia article that will come out in March 2012 (see attached galleys):

Shannahoff-Khalsa DS. Meditation: The Science and the Art (chapter 228), in The Encyclopedia of Human Behavior, 2nd Edition, Editor, Vilayanur S. Ramachandran, Elsevier, 2012.

And the technique as part of a 7-part protocol called “Treating the Addictive, Impulse Control, and Eating Disorders” was published in the two following books (PDFs of the cover jackets are available on request and advance acclaims for NIH funded scientists are on the cover jackets):

Shannahoff-Khalsa DS, Kundalini Yoga Meditation: Techniques Specific for Psychiatric Disorders, Couples Therapy, and Personal Growth, W. W. Norton & Company, New York, London, 2006 (a professional book written by invitation).

Shannahoff-Khalsa DS, Sacred Therapies: The Kundalini Yoga Meditation Handbook for Mental Health. W. W. Norton & Co. Inc, (due for publication March 2012).

While this technique claimed to be specific for addictions has been used widely in non-academic treatment circles, there are no RCTs to date to test its validity. However, there is a meditation technique specific for treating OCD that was tested in 2 clinical trials and the latter one was funded by the NIH Office of Alternative Medicine in 1994. The final results of that trial were published in (see attached):

Shannahoff-Khalsa DS, Ray LE, Levine S, Gallen CC, Schwartz BJ, Sidorowich JJ. Randomized Controlled Trial of Yogic Meditation Techniques for Patients with Obsessive Compulsive Disorders, CNS Spectrums: The International Journal of Neuropsychiatric Medicine, vol 4, no. 12, pp 34-46, 1999.

Along with preliminary results of that OCD RCT in (see attached):

Shannahoff-Khalsa DS, Yogic Techniques are Effective in the Treatment of Obsessive Compulsive Disorders, In: Eric Hollander & Dan Stein, eds., Obsessive-Compulsive Disorders: Diagnosis, Etiology, and Treatment, Marcel Dekker Inc., New York, pp. 283-329, 1997. (available upon request)

In addition, David Shannahoff-Khalsa was invited and funded by NIDA (David Shurtleff) in 2010 to give the following stand-alone 1 hr lecture:

"Kundalini Yoga Meditation Techniques Specific for the Addictions, OCD, Impulse Control Disorders, and Compulsive Behavior," National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Oct 15, 2010. This lecture had a slightly different name as advertised on NIH’s “yellow sheet.”

Also, the techniques for addiction and OCD are also taught at the Annual Meetings of the American Psychiatric Association in:

165th Annual Meeting, American Psychiatric Association, Full Day 6 Hour Accredited CME Course, “Kundalini Yoga Meditation Techniques for Anxiety Disorders Including OCD, Depression, Attention Deficit Hyperactivity Disorder, and Posttraumatic Stress Disorder” May, 2012, Philadelphia (to be presented).

This same Full Day 6 hr CME course also included teaching the OCD and addiction techniques to participants by Shannahoff-Khalsa at the American Psychiatric Association Annual Meetings in 2011, 2010, 2008, 2007, 2006, and 2005.

Therefore, I believe these achievements warrant substantial funding by the proposed new National Institute of Substance Use and Addiction Disorders as a well-designed professionally conducted RCT for at least one significant addictive disorder. An R21 study would not allow for the sufficient funding necessary to conduct a meritorious RCT.

The comment I would like to make is that in my 22 years of sobriety, the single biggest challenge to recovery (of the sort the proposed institute can study) is the prescribing practices of physicians and psychiatrists. I cannot tell you the number of times a physician has tried to give me an addictive drug (e.g. a benzodiazepine or a narcotic) even though I am always clear that I am in recovery. More remarkable is that even when I do the "on the spot" intervention with the physician, I have occasionally been challenged by the physician! Recovering people in doctor's offices or emergency rooms should not have to be in the position of educating their physicians about the addictive potential of, say, Atavan. I am well educated, confident and assertive, and yet have also occasionally felt bullied by physicians with their prescription pads. There needs to be better training of medical professionals about substance abuse and recovery.

In particular, I am gravely concerned about the number of people attempting recovery whose doctors give them benzodiazepines on a long term basis. I have never seen anyone recover from this because of the nature of the pharmacology*addiction*my doctor-tells-me-to dynamic. It is quite shocking. I would like to see a lot more research into the role that the benzos play in recovery and relapse (especially since the benzos play such an important legitimate role in detoxification management). I have tried to do research online and neither NIAAA or NIDA has a presence. This is a problem--the NIH institutes should be one of the first sites that come up (as it would be if I searched for, say, cancer or heart disease). Instead, it is a lot of wacko.com advice from people about how to titrate, how to withdraw, how to justify staying on them, and so on...

Finally, it would be useful to study pain management and recovery. Some of the most spectacular relapses I have seen have been by individuals who have a real need to use narcotic pain relievers (e.g. major surgery), but then who do not get proper supervision by the medical professionals in charge of their care. If I ever have need to be in a hospital, then I have a team of aggressive people poised to intervene on my behalf. This is because I have no confidence in the ability of the typical modern American health care provider to treat the real threat of relapse in recovering people appropriately.

The physical health field has numerous ways of testing patients to determine an accurate course of treatment and has the tools to measure the effectiveness of treatment along the way. These tests also help the patient see their progress and keep them committed to the process. The mental health field does not have such approach and is mostly based on expert opinion rather than on the quantitative testing. Both patients and doctors rely on a patient’s personal opinion and communication and due to the complex nature of the disorders, we continue to have high rates of inaccurate diagnosis, treatment, prescriptions and disillusioned patients dropping out of treatment. Neither drug, alcohol, gambling addictions or phobias have a consistent record of successful treatments and the field represent rather a personal art of some physicians than a publicly well established practice with out well established quantitative testing.

References Bickel, W.K. (2007). Behavioral and neuroeconomics of drug addiction: Competing neural systems and temporal discounting processes. Drug and Alcohol Dependence, 90S, S85-S91.

Epstein L.H., Salvy, S.J., Carr, K.A., Dearing K.K., & Bickel, W.K. (2010). Food reinforcement, delay discounting, and obesity. Physiology and Behavior, 14, 438-445.

Henningfield, J.E. (2011). Tobacco psychopharmacology and public health policy: it takes a community. Experimental and Clinical Psychopharmacology, 19, 249-262.

Higgins, S.T. (2004). Clinical implications of reinforcement as a determinant of substance use disorders. Annual Review of Psychology, 55, 431-461.

Loewenstein, G., Brennan, T., & Volpp, K.G. (2007). Asymmetric paternalism to improve health behaviors. JAMA, 298, 2415-2417.

Schroeder, S.A. (2007). Shattuck lecture. We can do better—improving the health of the American people. New England Journal of Medicine, 357, 1221-1228.

The majority of American adults that drink alcohol are not alcoholic but rather moderate drinkers. Therefore, this new institute must include the study of health benefits and risks associated with more moderate social and binge drinking.

Tobacco research should be included into the new institute.

Other addictions should be included (obesity, gambling, etc).

Funding for alcohol, tobacco and ilicit drug research should be allocated considering the impact of each of these in the public. Economic cost of alcohol abuse is significantly greater than that of other substances.

Removing fetal alcohol research to other institutes will have devastating effects on this area of research. It is critical that all aspects of alcohol research remain within this new institute. Fetal alcohol research needs to be within an institute that focuses its research program on how alcohol affects not only brain but various organ systems, immune function, behavior.

One conclusion I draw from these considerations is that the phenomena we study probably do not respect the institutional boundaries that seem to be Plan A for the new institute much better than they respected the existing NIAAA-NIDA-NIMH-NCI boundaries. The brain is one organ. Dividing “addictions” from other behaviors may be convenient for bureaucratic or other purposes, but as scientists we ultimately cannot avoid studying the brain as a whole. Thus, understanding how the broad spectrum of addictive, compulsive, Axis I, and personality disorders interweave seems to me to be the core challenge, and opportunity, for the new institute, with a lot of help from other institutes.

I also am concerned that the scope of the new addictions institute might be construed too narrowly in another way. I fear there is a real danger in calling the institute an “addictions” institute because the public perception of “addictions” is that it has to do with “addicts” who are totally different from the rest of us. When I say “public” I specifically want to include “congress.” As scientists we understand that alcohol and drugs harm a lot of people who do not even faintly resemble the stereotype of “addicts.” Think of teenagers driving shortly after their first experience with beer, or victims of fetal alcohol, tobacco, or illegal drug exposure. There are very important public health dimensions associated with alcohol and tobacco in particular that need to be protected in the transition to the new institute because they tend to fall outside the general public view of “addiction.”

A third opportunity/challenge for a new addiction institute would be to maintain a systems approach to the substances and behaviors under study. There is a “dopamine disease” focus that is popular among some addiction scientists today. While I would not want to minimize the importance of dopamine systems, alcohol in particular (but also tobacco and other substances) affect not only a variety of brain systems beyond dopamine, but also other organ systems that interact with the brain in ways that we only dimly understand. And effects on other organ systems are responsible for many of the most devastating health effects of alcohol, tobacco, and other abused substances.

Finally, social and policy research integration across the proposed span for the new institute presents special challenges. The public policy methods for preventing and/or minimizing the social harm of the two legal substances, alcohol and tobacco, differ greatly from those appropriate for illegal substances. It is less clear how differently social influence processes function across the span of substances, gambling, and other related behaviors. The importance of social processes is becoming increasingly clear (Stout, Kelly, et al., 2012), so uncovering the commonalities and differences in how social processes affect substance initiation, use patterns, and outcome across substances should be a fruitful area for research.

I personally have mixed feelings about the concept of a single addictions institute. There are possible synergies from combining (primarily) NIDA and NIAAA, but my reading of the scientific opportunities and challenges is that much more would be gained by the creation of a broader human behavior institute. I do not think it essential that we hasten to finalize the current proposed integration without taking time to consider the larger opportunity we would pass up or delay.

I hope these comments are of some value to the committee.

Shea, M. T., Stout, RL et al. (2004). "Associations in the course of personality disorders and Axis I disorders over time." Journal of Abnormal Psychology 113: 499-508. Phillips KA, & Stout RL. (2006) Associations in the longitudinal course of body dysmorphic disorder with major depression, obsessive compulsive disorder, and social phobia. Journal of Psychiatric Research;40:360-369 . Stout, R. L., Kelly, J. F, Magill, M., & Pagano, M. E. (2012). Association Between Social In?uences and Drinking Outcomes Across 3 Years. Journal of Studies on Alcohol and Drugs, 73 (3), 489-497

One conclusion I draw from these considerations is that the phenomena we study probably do not respect the institutional boundaries that seem to be Plan A for the new institute much better than they respected the existing NIAAA-NIDA-NIMH-NCI boundaries. The brain is one organ. Dividing “addictions” from other behaviors may be convenient for bureaucratic or other purposes, but as scientists we ultimately cannot avoid studying the brain as a whole. Thus, understanding how the broad spectrum of addictive, compulsive, Axis I, and personality disorders interweave seems to me to be the core challenge, and opportunity, for the new institute, with a lot of help from other institutes.

2) We are now just making headway on destigmatizing alcohol dependence. This is a very arduous task. There is fear that "lumping" the legal substance alcohol with many illicite substances would halt or reverse this destigmitazion process. That would not be good for public health. If the Institutes were to merge a large public awareness/marketing effort should be put forth to "destigmatize" alcohol dependence and differentiate it from othe substance dependence. Contrary to what some pundants and scientists believe, alcohol is still the most common, and perhaps treatable, substance addiction and in community samples it is far more prevalent, with causing considerably health care expenditures than most other substances except tobacco perhaps. Taken togehter with other societaly expenditures (auto accidents, fires, industrial accidents, domestic violence, murder, rape etc.) it is the most costly and deadly of abused substances. Therefore the largest share of the new Institute's budget should be directed towards alcohol research!

3) The pharmaceutical industry is just now becoming interested in investing in medications development for alcohol use disorders. This is not true of other addictions (except nicotine perhaps). There is concern that this momentum will be lost in a combined institute. This also relates to the stigma issue of point #2. Unless companies are supported in this fledging effort it will likely languish and reverse. This should be given a high priority whether NIAAA remains separate form NIDA or combined.

4)Screening for alcohol and other substance abuse in primary, and in some specialty care medicine, and offering treatment options is one of the highest public health care priorities. This needs to be supported, researched, and training made available in medical and other health professional (e.g. nursing, physician assistant) schools nationwide.This would include the use, and application, of various biomarkers for drinking and drug use with an attempt to translate research into practice where appropriate in both diagnostics and treatment.

5. Since alcohol (and many other substances) have known neurobiological effects they are prime candidates for pharmacogenomics. There is knowledge developing in this area - but not fast enough given the available technologies. A program where large numbers of individuals are genotyped and the reaction to alcohol (or other substances) under standard conditions, and possibly over developmental age and substance experience, should be started ASAP with an appropriate and large investment of funding. This process will likely lead to the most knowledge for the least investment. Genetic risk for variant reactions (e.g stimulation, euphoria, etc.) could be ascertained and individuals followed longitudinally to validate risk for developing addiction. This effort could be coupled ot brain imaging to enhance the knowledge on brain regional effects as it relates to genetic variability as well.

The field has a new wave of synthetic drugs. This problem has baffled the current health and criminal justice intervention models. Again,from a policy to practice states need model state drug laws and agencies need education and treatment approaches that are tested.

Last..youthful offenders are increasing at a rapid pace..what are the treatment engagement strategies that work

The new institute – working title: "National Institute of Substance Use and Addiction Disorders"

Thanks!

Additional issues that are not covered on the list in the RFA: 2) The effects of alcohol are not restricted to the brain, but are found in many organs of the body. Moreover, it has been shown that effects outside the CNS can impact the CNS--for example liver damage can impact CNS damage following alcohol exposure. The interrelationship among organ systems needs to be included. These issues affect both scientists and the public.

3) Alcohol has differential effects at low doses. However, it is unclear whether there are long-term consequences to low dose exposure or even what doses causes problems and the factors that determine what dose is "safe" for any given individual. The establishment of these factors and the understanding of the effects of moderate doses needs to be studied. These issues affect both scientists and the public.

4) Alcohol is somewhat unique in that there is less of an age-relatedness to alcoholism. For example, few elderly individuals are likely to go and try cocaine. However, increasing level of alcohol consumption are often found in older individuals. The effects of alcohol consumption on the health of older individuals should be explored. These issues affect both scientists and the public.

Are we doing justice to tax payers money, if we leave them in the dark regarding the public health effects of moderate and social drinking. Not to mention the intention to put it all under the umbrella of addiction (and labeling them as addicts)? Of note, there is already stigma attached to addiction. Will this "one size fits all" approach be more helpful or harmful regarding public health (including public perception)? Last, but not the least, please do not ignore the fact that these type of actions will shape the faith and trust of young investigators, such as myself, in the NIH funding system and mode of operation.

This approach is going to kill many interesting, ongoing avenues of alcohol research, which will not be funded by the new addiction institute or other institutes (e.g. moderate alcohol use, alcoholic liver disease).

To us (the research community), the reasons for this change seem to be based more on NIH politics and money rather than science, and doing the best for the public and public health.

This move will also be detrimental for investigators like me, who are new to the alcohol field, and have invested time and effort and obtained interesting results. This is particularly true for investigators studying liver and alcohol. We will be forced out of the system and be in a very vulnerable situation.

It is therefore obvious that in the long-term, this will prove to be a costly and harmful exercise, which should be re-considered and stopped.

Here's why:

1) Most high school and college students are not addicted to alcohol. Yet, they drink in a manner that puts them at risk and contribute substantially to a major public health problem that is costly in terms of dollars, a burden on public services (e.g., medical community, law enforcement), and a detriment to positive mental and physical health.

2) Even several drinks for a young person can contribute heavily to risky decisions and behaviors as we have observed from the numerous studies examining the relationship between drinking and consequences in adolescents and emerging adults.

3) Most of the consequences (i.e., sexual assault, vomiting, fights, property damage, arrests, DUI, riding w/a DUI, etc.) are not necessarily the consequences of an individual that is addicted to alcohol, but rather a result of poor alcohol-influenced decision making.

4) The focus on increasing the use of parent communications and increased protective behaviors are not the treatment modalities for individuals who are addicted to alcohol. However, numerous studies show the benefits of these approaches to reducing acute use of alcohol and the problems associated with this behavior.

5) The acute abuse of a drug such as alcohol observed for adolescents and young adults is very different from being addicted to the drug as are the determinants and methods of prevention/intervention.

Again, I urge you to consider adopting a wider lens beyond just addiction.

Here are our main concerns:

1) Most high school and college students are not addicted to alcohol. Yet, they drink in a manner that puts them at risk and contributes substantially to a major public health problem that is costly in terms of dollars, a burden on public services (e.g., medical community, law enforcement), and a detriment to positive mental and physical health.

2) Even several drinks for a young person can contribute heavily to risky decisions and behaviors as we have observed from the numerous studies examining the relationship between drinking and consequences in adolescents and emerging adults.

3) Most of the consequences (i.e., sexual assault, vomiting, fights, property damage, arrests, DUI, riding w/a DUI, etc.) are not necessarily the consequences of an individual that is addicted to alcohol, but rather a result of poor alcohol-influenced decision making.

4) The focus on increasing the use of parent communications and increased protective behaviors are not the treatment modalities for individuals who are addicted to alcohol, but are vital for primary and secondary prevention efforts.

5) The acute abuse of a drug such as alcohol observed for adolescents and young adults is very different from being addicted to the drug, as are the determinants and methods of prevention/intervention.

In this case, I would say the biggest concern is how the NIH's new institute plans to define these terms. If too clinically defined, it will preclude most of our current research, and any future research in this area, which impacts a large number of faculty and graduate students. More specifically, the NIAAA NRSA pre-doctoral training grants have been a wonderful resource and opportunity for our students--both through learning how to write a grant, and in the training the awards provide. The current restructuring proposal might prevent well-written grants and well-structured research projects from being funded, ultimately hindering our student training capabilities and professional growth within the field.

I propose an alternative title, for primarily 2 reasons: 1. The term “substance use” will preclude the potential in the future to include problem gambling (and perhaps other non-substance use disorders should enough data warrant inclusion). As the DSM-5 may very well move pathological gambling disorder/gambling addiction into the new diagnostic grouping along with substance use disorders, this makes sense to consider an institute name that can accommodate this as well. 2. The term “Disorders” is too exclusive. NIDA and NIAAA have long provided discovery and direction for topics not only relating to disorders themselves, but also hazardous use, risky use, as well as medical complications, etc. 3. You want a name that can stand the test of time and continue to represent an always growing and changing field.

Thus, I propose the following name, one that would also be shorter and have a more catchy abbreviation: “National Institute on Addiction-Related Conditions” or “NIARC” for short.

The term “addiction-related” affords flexibility as the field grows in the coming decades. It can accommodate all drugs of abuse, all behavioral issues (deemed appropriate in the future); as well as all related “conditions” such as risky drinking, medical complications, etc. Further, it has better face validity to the public in that the term “substance” is still a bit foggy for the public to understand what exactly that means, whereas addiction is a term more easily identifiable and understood.

There also needs to be a push for research that uses a systemic approach to examine alcohol/drug use going beyond the narrow scope of addicted populations. For example, research that uses social network methodologies to explore how an individuals' social network influences their risky alcohol use, risky sexual behavior, and alcohol related consequences (i.e. rape, injury to self/others, poor decision making).

In regards to using a network approach, social networks are associated positively and negatively with health and well-being. From a behavior change point of view, a number of theories suggest that a person’s social relationships can shape their intentions to act in particular ways through norms (subjective, Theory of Reasoned Action/Theory of Planned Behavior, injunctive, or descriptive) and through social support (instrumental or emotional). For this reason, many studies have attempted to shape people’s perceived norms or influence their social support in order to shape their behavior. For such studies to have the best chance of success, it is critical to investigate if different individuals develop different kinds of support networks, and if particular support networks are more likely to be associated with alcohol/drug use and alcohol related consequences (unwanted sexual encounters,injury, risky decision making.

In conclusion, if NIH wishes to support innovated research that will benefit the majority of individuals and society then 1) the term addiction needs to be more broad and inclusive and 2) systemic research designs should be supported(i.e. network analyses).

A related issue is getting insurance companies to pay for MAT - many do not.

Another issue is facilitating the development of addiction treatment programs that are staffed to address comorbidities. It is much easier and more effective to treat routine medical and psychiatric problems in one location rather than having to send patients to different providers for routine problems.

A final issue is continuing work on development of compounds with morphine-like analgesic potential that have no abuse liability. This is one of the holy grails of addiction research but work in that area seems to have stopped.

The most surprising and critical issue of the whole proposal is that both NIAAA and NIDA are succeeding and generating important findings with their current structure. The current plan tries to fix something that is working, and the result will be a long lasting damage in the scientific production of both areas of research.

While these 11 areas are essential to furthering basic knowledge about the science and social impact of addiction, and are therefore important to academic scientists and to increasing the archival literature, they will have (and have had) little impact on the "addicted" or "to become addicted" public because they fail to provide a tangible "real world" solution to addiction (i.e. they are largely of academic and public policy interest only).

On the other hand, we identify the two areas 4 and 7 in the RFI as being most responsive to the needs of the public, because they entertain producing a tangible product to address addiction (e.g. a "pill" someone could ingest to prevent and/or treat addiction). From the RFI, these are:

"Developing strategies to enhance stakeholder interest in developing medications to treat various addictions, including nicotine and alcohol;"

and

"Alleviating the translational bottleneck for treatments to move from the bench to the bedside to the community"

We offer for consideration the following additional obvious new area not yet considered by the NIH for the new institute:

"Developing new drugs and/or formulations with less abuse and/or addiction potential than existing marketed drugs (e.g. alternative pain therapies to existing marketed opiates used to treat pain that offer lower abuse/addiction potential)"

It is well known that the rise of prescription opiate addiction and deaths resulting therefrom is an urgent public policy concern with no obvious solution that will balance the legitimate needs of patients suffering from pain while preventing those who ultimately seek to abuse such drugs. One solution is the technological (i.e. scientific) development of new pain medications and/or pain medication delivery systems with lower abuse potential.

4 (as published in RFI): "Developing strategies to enhance stakeholder interest in developing medications to treat various addictions, including nicotine and alcohol;"

7 (as published in RFI): "Alleviating the translational bottleneck for treatments to move from the bench to the bedside to the community"

14 (newly presented to NIH herein): "Developing new drugs and/or formulations with less abuse and addiction potential than existing marketed drugs (e.g. alternative pain therapies to existing marketed opiates used to treat pain that offer lower abuse/addiction potential)"

Syntrix Biosystems, Inc. and other similarly situated private drug development companies are obvious stakeholders to execute on the above areas that have the highest-impact to the public. While the new institute will be able to leverage its SBIR program to partially tackle the above areas, such funds in total are generally limited, being only a few percentage points of the total extramural budget. In our opinion therefore, additional focused RFAs and/or PAs should be developed in the extramural budget of the new institute that are in addition to the SBIR program that would support development efforts in private corporations to conduct the translational research and clinical trials necessary to develop tangible products (i.e. a pill) that can eventually be used to treat addiction, or provide therapies will less addictive potential (e.g. pain medications as effective as opiates but with less addiction potential).

The policy arena radiates tension between inconsistent perspectives on the use of alcohol, tobacco and other drugs. Alcohol is a blessing and a curse. Opiates are valuable analgesics and illegal intoxicants. Possession and use of marijuana is a federal criminal offense that some states and communities ignore if the use is for medical purposes. Nicotine stimulates and relaxes; tobacco kills. Addiction is a brain disease; addicts are criminals. We seek to eliminate problems associated with the use and abuse of alcohol, tobacco and drugs while protecting the rights of industry to manufacture and market these products. Alcohol, tobacco and drug control policies in the United States are constructed from an admixture of state and federal legislation, voter referenda, judicial decisions, administrative regulations, local ordinances, program rules and practitioner licensing. The new institute must recognize that alcohol, tobacco, and drug use, misuse, and abuse reflect local, state, and federal policies and promote research to better understand how policy facilitates and inhibits the development and continuation of alcohol, tobacco, and drug use disorders and can support prevention, treatment and recovery.

The Robert Wood Johnson Foundation provides a role model for promoting policy research. Before closing in 2009, the Substance Abuse Policy Research Program (SAPRP) made 368 awards supporting investigations of the effects of policy on access to alcohol, tobacco and drugs and assessing the impacts of policy on access to treatment and prevention services. NIH and the new Institute have an opportunity to build on the SAPRP legacy and expand the potential for policy interventions in the prevention and treatment of alcohol, tobacco and drug use disorders.

Translational and Implementation Research

The Scientific Strategic Plan should embrace the scientific challenges associated with translation of basic research into clinical practice and the implementation of evidence-based practices in clinical settings. An institute that focuses on basic science will have little impact on prevention and treatment services and contribute little to addressing the public health consequences of alcohol, tobacco and drug use disorders. The Institute’s research portfolio needs to address the full spectrum of research to practice. Prevention and treatment services for substance use and addiction disorders have unique translational and implementation challenges and can serve as laboratories for facilitation of empirically-based practices. The treatment field remains ambivalent to the use of medication-assisted treatments even though the investments of NIDA and NIAAA in effective addiction medications are bearing fruit and more effective medications are emerging. Without scientific study of the translational and implementation research process, important science developments will have little influence on clinical practice. Translational and implementation research needs to be a central component of the Institute’s Scientific Strategic Plan.

Effectiveness Trials in Practice-based Research Networks

The 1998 Institute of Medicine report, Bridging the Gap Between Practice and Research: Forging Partnerships with Community-Based Drug and Alcohol Treatment, highlighted the need to partner with the organizations treating alcohol and drug use disorders in the design and implementation of trials that test the effectiveness of interventions in the complexity and chaos of the clinical settings. An institute that does not have a partnership of research and practice cannot lead the development and implementation of emerging interventions. The National Drug Abuse Treatment Clinical Trials Network has demonstrated the capacity of community-based addiction treatment providers to participate actively in the design, implementation and interpretation of data from clinical trials. The Scientific Strategic Plan needs to continue to prioritize a research and practice network that benefits from collaboration between practitioners and investigators, assesses the feasibility of using new interventions in practice settings, and documents the effectiveness of the interventions in clinical practice.

Fetal alcohol syndrome is a special topical area of research that will not be well served by any new agency on addiction, nor will it be well served being placed into NICHD or any of the other existing NIH agencies.

The original statement: • Understanding the mechanisms by which alcohol and other drugs of abuse increase risk for certain diseases (e.g. cancers), particularly when used in combination;

I believe could be broadened to state: "• Understanding the mechanisms by which alcohol and other drugs of abuse increase risk for certain diseases (e.g. cancers, viral infections, impaired fetal/newborn immunity, etc.), particularly when used in combination;"

Rationale for suggesting sheep as model for addiction/RSV studies:

Most commonly, RSV causes a mild upper or lower respiratory disease with cold-like symptoms but in a small percentage of patients, particularly the very young, severe disease can occur. Nearly every child in the United States has been infected with RSV at least once by age two. Because of its ubiquity, the low percentage of severe disease yields a significant number of hospital cases: 85,000-144,000 infants with RSV infection are hospitalized annually in the United States alone. This constitutes 20-25% of the pneumonia cases and up to 70% of all bronchiolitis cases in the hospital. Treatment currently is limited to supportive care and one of two FDA-approved treatments. Two major stumbling blocks in development of preventative and treatment have been the disastrous initial vaccine clinical trial and the lack of an available, clinically relevant model of human disease. Rodents, while a valuable tool in RSV research, undergo post-natal alveolar development as opposed prenatal alveologenesis that occurs in humans and sheep. Additionally, sheep and humans share a number of upper and lower airway traits including: airway branching pattern, nasal lymphoid tissue distribution, alveolar size, submucosal gland type and distribution, cartilage distribution, sensory nerves, airway capillary physiology, mast cell distribution, mucus-secreting cells, histamine effects, and cough/wheeze response. Natural RSV disease occurs in cattle and sheep with bovine respiratory virus (bRSV) and has a similar presentation: seasonal outbreaks of highly contagious, mild respiratory disease with infrequent severe disease that occurs in conjunction with other pathogens. A bovine model of RSV infection has been used by a number of groups and is useful in mimicking human disease, but limited by the cost of feed and housing and typical birth of a single offspring in cattle. Additionally, there is current use of a number of efficacious vaccines in cattle. Sheep are a particularly attractive model because of their smaller size, reduced cost, and increased offspring/parity when compared to cattle, and more human-relevant pulmonary development and structure than rodents. Additionally, they can be born pre-term (90% gestation) with a high rate of survival. These features make sheep/lambs the ideal candidate model for maternal addiction studies.

I feel it is important that this new institution also endorses the need to develop better animal models of maternal ethanol & nicotine consumption [addiction] and its association with increased fetal/newborn susceptibility to viral diseases, such as RSV.

Thank you for considering these ideas.

For physicians/Scientists: 1-Specific training and curriculum in the field of Addiction Medicine for both general and child psychiatry residency training programs by formal didactics during training as well as workshops/CMEs. 2- Availability of testing kits in abundance for urine toxicology in primary care physician offices, mental health professional offices.

In particular, when a provider attempts to find information on the life expectancy for someone with opioid dependence, we are unable to do so easily. Or the number of deaths believed to be caused by a combination of alcohol and benzodiazepines. Basic statistics rather than very narrow research are in need from a psychoeducational perspective and the Government should remember that education is an important part of addiction treatment and intervention and we need an unbiased and reliable database of information. If it can't reasonably be interpreted or analyzed by the reader then it's essentially useless information.

Mortality Rates Rates of individuals with each diagnosis that experience organ failure Rates of individuals with each diagnosis who experience early onset of dementia Rates of individuals with each diagnosis who experience trauma as opposed to a control group Divorce rates DUI rates Rates of individuals who contract STD's Overdose rates ER use rates Incarceration rates Relapse rates when anticraving meds are used % of domestic violence incidents where specific substance abuse was involved Suicide rates by substance Co-occurring disorder rates by substance Rates of uncontrolled HTN related to substance use

...

There are a lot of people who get better on their own. We need to understand under what conditions is treatment really beneficial.

Many investigations have the goal of keeping people in treatment. That is well and good, but what impact does treatment have on employment, family relationships, education, crime, etc. We have to move beyond a "more is better" process analysis to an assessment of impact on real outcomes.

The wide variation in provider quality suggests the need to minimize such variation so a customer can feel that service quality is highly predictable. Technology can help minimize variation in quality. Research and development need to create and evaluate such technologies.

There are thousands of apps and other technologies that suggest that they can help people deal with addictions. Which ones really help and how can a customer choose between the myriad of options.

Given the limitations on resources, the delivery of addiction treatment can't remain the same. Many families if properly prepared could make an enormous difference in recovery. They need respect, training and support and yet the field does not involve them or do they prepare them to be effective partners in recovery.

NIDA's last strategic planning document a few years ago neither mentioned the word overdose nor strategies for nor the role of mediating injection-related harm. This ignoring of massive causes of morbidity and mortality from drug use must stop. This new agency must be free from the distortions and death promotion that has existed of recent.

Drug-related morbidity and mortality must be among the highest priority of this agencies efforts.

and

An urgency to apply the best investigative sciences to the true nature of the relationship between humans and their multiple intoxicants.

The critical issue at hand is the need for inclusion of pathological gambling in the proposed institute, and the negative impact such an oversight would have on the general public and society as a whole as well as those directly affected by this addiction.

In addition, people who inject drugs, or who use large amounts of drugs or alcohol, are at high risk for acquiring and transmitting as-yet-unknown emerging diseases. If the new institute does not include capacity to conduct research among them, we may be delayed in learning these new diseases even exist. (We lost several years on HIV due to such delays--see Friedman, Samuel R.; de Jong, Wouter; Rossi, Diana; Touzé, Graciela; Rockwell, Russell; Des Jarlais, Don C.; Elovich, Richard. 2007. Harm reduction theory: Users culture, micro-social indigenous harm reduction, and the self-organization and outside-organizing of users' groups. International Journal on Drug Policy 18:107-117.) We will also have great difficulty getting research approved by other institutes whose staff know little or nothing about working with samples of substance users.

NIAAA has been doing an exemplary and well balanced job. Alcohol research will not benefit if alcholic liver disease research is farmed out to DK, heart research to HL, etc. More likely, such research of such great societal important will simply not be done, because the priorities of these other institutes are elsewhere.

The proposed merger is motivated not by an effort to improve alcohol research, but by the desire of NIH leadership to make room for new unrelated institutes. This is a bad reason. Don't do it.

We also need to encourage research that addresses underserved and disadvantaged subpopulations at higher risk of addictions and who face greater barriers to treatment and recovery, such as women, the poor, and racial/ethnic minority groups. This institute should encourage research on barriers to alcohol treatment for such groups including their use of informal supports such as 12 step recovery programs for addictions.

This creation must be accompanied by administrative savings and zero decrease in dollars going to support research, both intramurally and extramurally. In fact, given the administrative savings. funding for research should increase.

More than 100 million Americans suffer from chronic pain, according to the Institute of Medicine. Chronic pain affects more people than cancer, heart disease, and diabetes combined yet receives far less funding for research. In addition, the increase in the use of prescription opioids to treat pain has brought a significant public health problem in the form of substance abuse, addiction, and overdose deaths. The challenge is to understand pain better so as to treat it more effectively without the attendant public health risk posed by substance abuse.

Patients who suffer from chronic pain and the doctors who treat them urgently need safer opioid and non-opioid alternatives to reduce the risk of abuse, addiction, overdose, and diversion to nonmedical use. Newer, safer therapies have shown promise but need further examination to determine their effectiveness in a variety of populations. Recent genetic findings show that individuals vary in their medication needs and pain response, suggesting that further research into these areas could produce new methods of treatment based on genetic profiles. Research indicates that addiction and pain may utilize common pathways in the central-nervous system and feed each other. These are just a few of the promising areas that are ripe for future research.

A dedication to funding quality research can yield great benefits. For example, in the War on Cancer, increased research has produced greater understanding of cancer biology and facilitated the development of improved treatments that are able to halt many cancers. Pain is similar in its complexity and the toll it takes on the public health. As such, it is deserving of the same commitment.

More than 100 million Americans suffer from chronic pain, according to the Institute of Medicine. Chronic pain affects more people than cancer, heart disease, and diabetes combined yet receives far less funding for research. In addition, the increase in the use of prescription opioids to treat pain has brought a significant public health problem in the form of substance abuse, addiction, and overdose deaths. The challenge is to understand pain better so as to treat it more effectively without the attendant public health risk posed by substance abuse.

Patients who suffer from chronic pain and the doctors who treat them urgently need safer opioid and non-opioid alternatives to reduce the risk of abuse, addiction, overdose, and diversion to nonmedical use. Newer, safer therapies have shown promise but need further examination to determine their effectiveness in a variety of populations. Recent genetic findings show that individuals vary in their medication needs and pain response, suggesting that further research into these areas could produce new methods of treatment based on genetic profiles. Research indicates that addiction and pain may utilize common pathways in the central-nervous system and feed each other. These are just a few of the promising areas that are ripe for future research.

A dedication to funding quality research can yield great benefits. For example, in the War on Cancer, increased research has produced greater understanding of cancer biology and facilitated the development of improved treatments that are able to halt many cancers. Pain is similar in its complexity and the toll it takes on the public health. As such, it is deserving of the same commitment.

Caffeine is easily the most widely consumed psychoactive substance in history (James, 1991, 1997). Consumption typically follows a lifelong course, transcending almost every barrier, including age, gender, geography, and culture. Its prevalence of use greatly exceeds that of any other drug, including nicotine, alcohol, and the panoply of non-legal drugs of abuse. Indeed, caffeine is unusual amongst psychoactive compounds in being part of the daily diet of most people on Earth. Moreover, caffeine is essentially alone amongst psychoactive compounds in being unregulated in most jurisdictions with respect to legal-age of consumption. While being of profound importance in its own right, knowledge of caffeine has and will continue to enhance understanding of substance use and addiction disorders of every description.

With reference to points highlighted in the “preliminary list of potential scientific opportunities and public health needs” contained in the NIH Notice NOT-OD-12-045, key scientific and public health issues and challenges concerning caffeine include the following:

• The NIH preliminary list of potential scientific opportunities and public health needs makes repeated mention of the importance of advancing knowledge of drug interactions. In that regard, it would be a grave oversight to omit caffeine from the list of priorities included in the proposed Institute’s Scientific Strategic Plan. Since almost the entire population consumes caffeine regularly, it necessarily follows that most drug interactions of interest (e.g., alcohol with therapeutic drugs; alcohol with opiates, stimulants, hallucinogens, or inhalants) occur against a background of potential interactions with caffeine. Knowledge of interactions between the innumerable drugs that individuals simultaneously ingest must necessarily be incomplete if account is not taken of the likely presence of caffeine as a background drug of use. Accordingly, knowledge of interactions between caffeine and other drugs is of great importance both scientifically and for reasons of public health.

• Increasingly, caffeine is being seen as a relevant variable in the development of patterns of use of other legal and non-legal drugs. For most individuals, caffeine is the first drug to be regularly ingested, with consumption often beginning in early childhood (e.g., through the regular consumption of cola drinks). Indeed, population studies show that caffeine is a strong predictor of smoking and alcohol use during adolescence (James et al., 2011; Kristjánsson et al., 2011). Though regular caffeine consumption typically precedes usage of other drugs, research is needed to examine the possible causal role of early caffeine exposure in the developmental trajectory of later usage of other drugs.

• Because brain structures involved in the regulation of higher-order cognitive functions and emotional experience are among the last to mature, not fully developing until a decade after mid-adolescence, substance use during childhood and adolescence may pose risks for cognitive and emotional development. The prevalence of caffeine consumption amongst children is particularly high (in excess of 70% in the United States and elsewhere), yet the possible effects of such exposure to brain development, and concomitant cognitive and emotional development, in children is substantially under-studied. One example of the importance of redressing this shortfall in knowledge is a recent study which found that increased daily caffeine consumption amongst adolescents is associated with increased expression of anger (Kristjánsson et al., 2011).

• The advent of energy drinks and growth in the number of brands of soft drinks that contain caffeine has been accompanied by a pronounced increase in the marketing of those products to young people, thereby giving rise to questions about the biobehavioral implications of increased consumption of caffeine by children and adolescents. For example, although adolescent smoking and alcohol use have long been known to predict adjustment problems during adolescence, including poorer academic achievement, recent research in a large adolescent population (N > 7,000) found caffeine consumption to be a stronger independent predictor of poorer school performance than smoking and alcohol use separately and combined (James et al., 2011; Kristjánsson et al., 2011). Furthermore, findings indicated that the mechanism responsible for the negative effect of caffeine on academic achievement was likely to involve daytime sleepiness, a finding that is consistent with the known pharmacological actions of caffeine, including its direct disruptive effects on nighttime sleep and the sleepiness-inducing effects of daytime caffeine withdrawal (James & Keane, 2007; Keane et al., 2007; Keane & James, 2008).

References Ferré, S., Jensen, M. B., Kempf, K., et al. (2011). What do you see as the main priorities, opportunities, and challenges in caffeine research in the next five years? Journal of Caffeine Research, 1, 5-12. James, J. E. (1991). Caffeine and Health (pp. 430). London: Academic Press. James, J. E. (1997). Understanding Caffeine: A Biobehavioral Analysis (pp. 227). Thousand Oaks, CA: Sage Publications. James, J. E. & Keane, M. A. (2007). Caffeine, sleep and wakefulness: Implications of new understanding about withdrawal reversal. Human Psychopharmacology: Clinical & Experimental, 22, 549-558. James, J. E., Kristjansson, A. L., & Sigfusdottir, I. D. (2011). Adolescent substance use, sleep, and academic achievement: Evidence of harm due to caffeine. Journal of Adolescence, 34, 665–673. Keane, M. A., & James, J. E. (2008). Effects of dietary caffeine on EEG, performance, and mood when rested and sleep restricted. Human Psychopharmacology: Clinical & Experimental, 23, 669-680. Keane, M. A., James, J. E., & Hogan, M. J. (2007). Effects of dietary caffeine on topographic EEG after controlling for withdrawal and withdrawal reversal. Neuropsychobiology, 56, 197-207. Kristjansson, A. L., Sigfusdottir, I. D., Allegrante, J. P., & James, J. E. (2011). Adolescent caffeine consumption, daytime sleepiness, and anger. Journal of Caffeine Research, 1, 75-82.

• Interactions between caffeine and other drugs;

• the potential causal role of early caffeine exposure in the developmental trajectory of later use of other drugs;

• the possible risks to developing brain structures of caffeine consumption during childhood and adolescence, and the concomitant implications for cognitive and emotional development; and

• the implications for public health of an increase in biobehavioral effects associated with the greatly increased range of caffeine products that are marketed specifically to children and adolescents.

In addition to the aforementioned priorities, it is profoundly important that the Scientific Strategic Plan of the proposed National Institute of Substance Use and Addiction Disorders also includes caffeine as a priority to be examined for the role that lifelong exposure may have in the development and course of major chronic diseases, including the following:

• Well-controlled experimental studies have shown definitively that dietary caffeine produces modest long-term increases in blood pressure (i.e., tolerance develops only partially to the acute pressor effects of the drug) (e.g., James, 1997, 2004, 2010). Nevertheless, epidemiological studies tend to show that, if anything, caffeine or caffeine beverages (notably, coffee) may provide modest protection against cardiovascular disease. However, epidemiological studies of caffeine are highly vulnerable to sources of confounding due to uncontrolled individual biological, behavioral, and social covariates of dietary caffeine consumption. Hence, research is needed to clarify whether dietary use of caffeine contributes to cardiovascular disease, and if not, what are the protective factors in caffeine beverages that counteract the likely long-term negative effects of caffeine on blood pressure.

• A major scientific and population health dilemma currently exists in relation to the possible involvement of caffeine in glucose metabolism and the development of type 2 diabetes (Lane, 2011). On the one hand, well-controlled experimental studies show that caffeine interferes with glucose metabolism, while on the other hand, there are epidemiological studies suggesting that coffee may protect against development of type 2 diabetes. This dilemma is in need of urgent resolution, especially considering the current pronounced increase in prevalence of type 2 diabetes.

• A further controversy of no less importance exists in relation to the putative neuroprotective effect of caffeine. The prospect that caffeine or caffeine beverages may offer protection against cognitive aging, in particular, has attracted considerable interest, especially in light of epidemiological findings supporting an inverse (i.e., protective) association between coffee and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. However, any actual benefit remains unclear, as evidenced by recent findings from Scotland suggesting that epidemiological evidence of caffeine neuroprotection may be spurious, being the result either of confounding or reverse causation (Corley et al., 2010). The counterevidence is distinctive because it derives from a large cohort of elderly participants (70+ years) whose IQ had been comprehensively measured at age 11 years. Individuals with higher childhood IQ performed better in adulthood than those with lower childhood IQ, irrespective of caffeine intake. Moreover, higher-IQ children consumed more caffeine/coffee in adulthood than lower-IQ children, a lifestyle-related choice by individuals possessing higher IQ and associated higher social status. Analyses showed that coffee-related superior cognitive ability in adulthood (an apparent protective effect of caffeine/coffee) was the result of lifelong cognitive advantage stemming from superior cognitive ability in childhood. In fact, caffeine/coffee had no protective effect for cognitive function. However, given the many other studies, both animal and human, that point to a possible neuroprotective effect of caffeine or coffee, the question is in need of further urgent examination.

• There is a large literature and much interest in caffeine as a possible sleep-loss prophylactic. However, sleepiness is a confirmed effect of caffeine abstinence (Juliano & Griffiths, 2004), and much of the relevant evidence of caffeine sleep prophylaxis derives from studies that inadequately controlled for confounding arising from reversal of abstinence-induced sleepiness (James & Keane, 2007). Indeed, there is evidence that caffeine use may actually be hazardous under certain circumstances where persons may experience unrelieved caffeine abstinence-induced sleepiness (James, 2012). Given that caffeine has been widely advocated as a sleep-loss prophylactic (e.g., for shift-workers of every description, airline pilots, air traffic controllers, military personnel, nurses, nuclear power plant operators, and long-distance hauliers), further urgent research is needed to evaluate comprehensively its net effects on sleep-wake cycles.

References Corley, J., Jia, X., Kyle, J. A. M., et al.. (2010). Caffeine consumption and cognitive function at age 70: The Lothian Birth Cohort 1936 Study. Psychosomatic Medicine, 72, 206-214. James, J. E. (1997). Caffeine and blood pressure: Habitual use is a preventable cardiovascular risk factor. The Lancet, 349, 279-281. James, J. E. (2004). A critical review of dietary caffeine and blood pressure: A relationship that should be taken more seriously. Psychosomatic Medicine, 66, 63-71. James, J. E. (2010). Caffeine. In B. Johnson (Ed.), Addiction medicine: Science and practice. New York, NY: Springer, pp. 551-583. James, J. E. (2012). Caffeine psychopharmacology and effects on cognitive performance and mood. In L. Riby, M. Smith, & J. Foster (Ed.), Nutrition and cognitive performance. London: Palgrave Macmillan, pp. 270-301. James, J. E. & Keane, M. A. (2007). Caffeine, sleep and wakefulness: Implications of new understanding about withdrawal reversal. Human Psychopharmacology: Clinical & Experimental, 22, 549-558. James, J. E., & Rogers, P. J. (2005). Effects of caffeine on performance and mood: Withdrawal reversal is the most plausible explanation. Psychopharmacology, 182, 1-8. Juliano, L. M., and Griffiths, R. R. (2004). A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology, 176, 1-29. Lane, J. D. (2011). Caffeine, glucose metabolism, and type 2 diabetes. Journal of Caffeine Research, 1, 23–28.

Training should specifically include education about alcoholism and addiction. This education should focus on several areas: 1. Meaningful curriculum in this area during medical school and in the curriculum of nursing and pharmacy schools; 2. Continuing education, principally for general practitioners, internists, and nurses; 3. Education concerning issues of prescribing pain medication to alcoholics and drug addicts who are in recovery; 4. Education concerning non-medical resources in treating alcoholism and addiction, e.g., Alcoholics Anonymous, and an acknowledgment and acceptance of its potential benefit; and 5. establishing a system or platform which physicians could use as a resource in diagnosing and treating alcoholism and addiction.

It is important to study the epidemiology and etiology of drug and alcohol addiction/dependence and various intervention modalities. In my view, however, it is equally important to study the adverse health effects of drug and alcohol abuse. Without knowing the adverse health effects of these addictions it is meaningless to study all other aspects of drug abuse. Only research on adverse health effects of substance abuse will inform the public as to why not to abuse alcohol and drugs of abuse.

It is necessary to have a division or some other organizational entity clearly designated to deal with studies of the impact of drug and alcohol addiction on medical/health conditions and the spread of infectious diseases and other conditions that might impact on physiological systems, including role of nutrition in drug addiction and infectious diseases; morbidity, co-morbidity and mortality associated with drug use/abuse and /or infections; pathogenesis of drug abuse-associated HIV/AIDS and other co-occurring or opportunistic infectious disease, as well as others in this category.

Currently, the general model is to fund research that can result in the production of Evidenced-Based practices and protocols for their implementation (e.g., solution focused, motivational interviewing, cognitive-behavioral). One issue is the continued finding of lack of sustainability in the real world even if the setting administration is committed and good training and supervision is provided.

I believe this raises the issue of resistance to protocols that often lead to what I refer to as mechanical practice. I believe it would be helpful to fund efforts (my own included obviously) to develop models that integrate the best of specific findings without requiring individual rigid conformity to any one protocol. This would be an integrated approach that would in effect develop a science that frees artistry instead of one that limits it.

Associated with this would be another related area of research that explores the mechanisms of "mutual aid" within treatment groups. Mutual aid models can incorporate EBP practices without being bound to a specific protocol. Mutual aid processes can also be integrated into existing group EBP's. The emergence of our understanding of the power of group alliance, in addition to therapeutic alliance, is an area for exploration.

Finally, the exploration of the use of social media (e.g., Facebook)as a therapeutic tool should also be given attention. In addition to in-setting groups cyber groups can also create a system of support for clients struggling with addition issues including prevention and recovery.

1. The development of integrated approaches using evidenced-base practice model without strict adherence to one models' protocols.

2. Exploration of the dynamics of the mutual aid process in groups including leader interventions and how they affect the development of both the therapeutic alliance and the group alliance and their impact on treatment retention and other outcomes.

3. The use of social media as a tool for prevention and treatment. This would require developing tools for content and process analysis of social media interventions (at least one already exists).

The justifications for these suggestions were addressed in comment 1. Thank you for the opportunity to provide input.I would be glad to provide further information if requested.

Lawrence Shulman, MSW, Ed.D, Professor and Dean Emeritus of the University at Buffalo School of Social Work.

Critical point 2. Prevention must remain a priority. Establishment of a new combined institute should be used as an opportunity to strengthen NIH’s prevention portfolio. Prevention has demonstrated significant impacts in reducing onset and progression of substance abuse and it is essential that NIH not lose this focus (cites). Prevention is a national priority in the Obama administration and recognized as critical to the nation’s health. A recent report (2009) from The Institute for Medicine calls for Continued research on both the efficacy of new prevention models and real-world effectiveness of proven prevention and wellness promotion intervention as well as adaptation of research-based programs to cul¬tural, linguistic, and socioeconomic subgroups. I believe that the new institute’s mission statement must include an emphasis on prevention. I strongly endorse that the new institute elevate prevention to a research branch with funding allocated to alcohol and drug abuse prevention research at least equal to, and ideally greater than, the sum of the current levels at NIAAA and NIDA. This branch should also work to focus on translational research of prevention programs into real world settings. Prevention programming is a primary driver of the national economic benefits of substance use research investments.

Critical point 3. Drug and alcohol use are social behaviors. The proposed strategic plan over-emphasizes biological science compared to social and behavioral science. Substance use and abuse, particularly of alcohol, usually occur in social situations. History, media, and social currents have made drug use a part of our national psyche. Both currently and historically, use of specific drugs has been linked to identification with particular social groups, movements, or philosophies. Research suggests that initiation of these behaviors is largely environmentally determined, and that socio-cultural environments (e.g., policy, peers, family) play pivotal roles in the initiation and, maintenance of, and desistence from drug use, abuse, and dependence. Certainly there is an interplay of environmental and biological influences in the development of addiction, however, to downplay the social, cultural, and psychological aspects of substance use disorder is a fundamental exclusion that will severely weaken efforts at prevention and treatment, and diminish the national economic contribution of work supported by the new institute.

Critical point 4. Integration with the NIH Roadmap. The new combined institute should have a clear plan for implementation of the NIH Roadmap for the Science of Behavior Change; for example, it could be a plan for how the behavioral sciences will be integrated into the biological and neuroscience portfolios.

Critical point 5. Interdisciplinary research is critical. Research on prevention and treatment of alcohol and drug abuse requires maintaining an interdisciplinary, multilevel perspective that takes into account comorbid disorders, such as mental health issues, and recognizes the role of social and environmental factors. It will be important as the two institutes combine that there is a strong commitment to interdisciplinary research.

Point of Clarification. What qualifies as “non-addiction research”? Does “non-addiction research” include such things as HIV sexual risk behavior, health promotion and positive youth development interventions (that may have a number of benefits, including reduced or delayed drug use), and research on use or misuse that does not meet criteria for abuse or dependence (e.g., binge drinking)? Do these research areas fit into the new Institute or will they be referred elsewhere?

June 12–14, 2006 Bethesda, Maryland

Conference Home Final Statement | PDF Program & Abstracts (PDF) Archived Videocast Day 1 | 2 | 3 Evidence Report Planning Committee | Panel Additional Information Documents in PDF format require the Adobe Acrobat Reader®. If you experience problems with PDF documents, please download the latest version of the Reader®.

Conference Scope

The State-of-the-Science panel assessed the evidence on the following conference questions:

1. What are the effective population- and community-based interventions to prevent tobacco use in adolescents and young adults, including among diverse populations? 2.What are the effective strategies for increasing consumer demand for and use of proven, individually oriented cessation treatments, including among diverse populations? 3.What are the effective strategies for increasing the implementation of proven, population-level, tobacco-use cessation strategies, particularly by health care systems and communities? 4.What is the effect of smokeless tobacco product marketing and use on population harm from tobacco use? 5.What is the effectiveness of prevention and of cessation interventions in populations with co-occurring morbidities and risk behaviors? 6.What research is needed to make the most progress and greatest public health gains nationally and internationally?

The research portfolio of the new institute must include health promotion. Alcohol is unique in many ways with its health promoting effects at low doses (in the majority of the adult population) and dangerous effects with excessive use. Educational programs (and their evaluation) are critical for the youth and public at large.

The National Institute on Alcohol Abuse and Alcoholism has utilized a “systems biology” approach to its efforts addressing the impact of alcohol on the entire body and organ systems. This has served research well since alcohol has such a wide array of effects on the organism. There has been some suggestion that the new institute would not fund certain areas of alcohol research (prenatal alcohol exposure and end organ damage as examples), but instead send these to other institutes. This type of isolation would have devastating effects on these areas of alcohol research. It is critical that all aspects of alcohol research remain within this new institute. Fetal alcohol research, as an example, needs to be within an institute that focuses its research program on how alcohol affects not only brain but various organ systems, immune function, behavior, etc.

Since a major component of the new institute will have a focus on addiction, it is important that the many forms of addiction that may share underlying mechanisms be part of this new institute. This must therefore extend beyond alcohol and other drugs to include other addictions that have a tremendous cost to society including nicotine (smoking), gambling, overeating, shopping, and internet or gaming. A number of these are currently housed in other institutes and the logical if not necessary approach would be to transfer them to this new institute.

There has been some suggestion about removing certain areas of alcohol research (like developmental alcohol exposure) to other institutes. This type of isolation would have devastating impacts. A number of my colleagues at Indiana University – Purdue University Indianapolis have active research programs investigating alcohol’s prenatal effects on brain development, and I am developing a new line of investigation along these same lines. Moreover, one of my current focuses is on alcohol sensitivity and intake during the critical developmental period of adolescence. It is critical that all aspects of alcohol research, including developmental alcohol research, remain within this new institute. Such a structure will be key if we are to better understand the social and biological impacts of developmental alcohol exposure, as well as identify intervention and treatment strategies for developmental alcohol exposure. Such work needs to reside within an institute that focuses its research program on how alcohol affects not only brain development, but various organ systems, immune function, behavior, etc. At present, it isn’t clear what institute would fund developmental alcohol research.

Increase effectiveness of evidence-based practices that reduce tobacco and other substance use for minority, low socioeconomic status, and LGBT populations.

Improve access and availability of community and clinical interventions/treatments to minority, low socioeconomic status, and LGBT populations.

Increase provider sensitivity and competence to deliver evidence-based practices to diverse cultural, linguistic, and geographically dispersed groups.

Increase opportunities for research training across diverse ethnic groups.

In addition to the specific areas of interest outlined in the RFI, other topics of relevant importance are listed below. Each of these is particularly important to nicotine dependence, but is equally important to study for other addictions: ? Better understanding the mechanisms through which treatments work, including identifying the “active ingredients” of multi-component interventions. ? Understanding how to leverage health care systems to best meet the needs of smokers and other substance abusers. ? Identifying more cost-effective, population-based interventions which can serve as a first line of intervention. This is particularly for prominent substances of abuse such as nicotine and alcohol. ? Developing effective behavioral interventions that are targeted to specific sub-populations, based on psychiatric or other illness comorbidities (e.g., depression, HIV, and other chronic illnesses). ? Understanding how to leverage new information technologies to provide more cost-effective treatment and reach a broader population (e.g., smart phones, text messaging, secure messaging linked to electronic medical records, Internet-based programs, etc.).

Additionally, I believe it is important to continue our investment in tobacco control. Tobacco is the leading addictive substance responsible for morbidity and mortality in the US and, as such, warrants particular emphasis in the new Institute.

These three areas are particularly important to me. I am a graduate student investigating execution function, mental health, substance use and abuse in adolescents. We need more funding and research in youth prevention because it will result in more knowledge and less use of young people who will also be less likely to use and abuse substances as adults, which in turn will lessen the demands on the recovery and mental health system. Ripple effect. Prevention will ease the demands on everyone down the line. Prevention will result in not having to work with people with concurring mental disorders that have developed due to heavy substance abuse. Effective prevention would result in less funds needed for recovery programs and homes and instead directed to help the next generation have a far stronger and healthier start. To focus on prevention makes sense now and in the long run.

Fetal alcohol spectrum disorders is the major reason for mental retardation in the US. For years the researchers across different scientific displines have worked hard to understand the impact of prenatal alcohol exposure and prevention and treatment methods. In addition, FASD directly increases addiction risk later in life. Therefore, it is important to keep

• We fully support the NIH commitment to excellent science, but wish to restore the balance between scientific rigor and relevance to real world problems. We think the gap has grown larger in the last decade, and we would like to increase NIDA’s commitment to bidirectionality. The NIDA CTN represents a remarkable opportunity for community treatment providers and scientists to work together to tackle the challenges faced in addiction treatment. This outstanding opportunity has not been fully realized and the new institute should renew the commitment to a bidirectional approach to improving treatment, using science as the vehicle.

• The current NIH emphasis on translational research reflects the recognition that there is too large a gap between science and practice. We think community treatment providers should be included in the formulation of the research questions and offer practical implementation considerations throughout the process. The CTN provides a robust infrastructure for this type of research and the historical embargo on conducting dissemination work within the CTN has led to a missed opportunity.

• Medications are tools, not solutions, in the treatment of SUDS. Diminishing emphasis on psychosocial interventions reflect a disregard for the real world problems of our patients and the need to address these in a comprehensive way. Behavioral interventions may work better than medications, or the combination of the two may work better than either alone. It is important to restore more balance to the research portfolio.

If this was not an oversight--and HIV was omitted by intent--then it is a very poorly conceived approach.

The discovery that drugs act as potent reinforcers by Charles Schuster (a former NIDA director), Roy Pickens, and Travis Thompson transformed addiction science and led to a range of evidence-based treatments that are still being disseminated across a multiplicity of settings. Basic research also gave birth to pre-clinical models to isolate and assess novel behavioral and pharmacotherapies for addiction.

Cutting-edge basic behavioral research continues on a range of topics in addiction. This work includes the influence of delay discounting on choice for drugs and other risky behavior, the role of associative processes in substance abuse and relapse, the importance of conditioned reinforcers in drug use, and the behavioral economics of substance abuse. Thus, behavioral research continues to transform our understanding, and it promises to lead to new strategies to prevent and treat addiction.

WE URGE THE NEW NISUAD TO PRESERVE A SIGNIFICANT ROLE FOR BASIC AND TRANSLATIONAL RESEARCH OF BEHAVIORAL PHENOMENA. In addition to the behavioral research described above, advances in neuroscience and genetics are increasingly being linked with basic behavioral phenomena. It is truly exciting when behavioral science and allied disciplines come together to form a deeper understanding of addiction. But these advances cannot occur without continued support for basic behavioral research. In any research portfolio, at some point the question will be asked about the behavioral significance of the phenomena under study. Answering this question will require basic behavioral research in animals and humans.

Critical issues that basic behavioral research can address include:

• THE ROLE OF CHOICE AND BEHAVIORAL REGULATION IN SUBSTANCE ABUSE. This includes the choice between drug use and other activities, self-control, delay discounting, modulation of incentive motivation, and response-inhibition in both animal models and in people.

• THE TRANSITION FROM TREATMENT TO COMMUNITY. The point at which an individual returns to the environment in which abuse occurred is a period of great vulnerability. We need to understand the basic processes of how such environments foster use and how to build resistance to these influences.

• THE ROLE OF ASSOCIATIVE PROCESSES, INCLUDING CONDITIONED REINFORCEMENT AND OCCASION-SETTING. These environmental factors contribute to the development of abuse, foster and enhance the impact of addictive substances and activities, and are critical determinants of relapse.

• THE DEVELOPMENT OF QUANTITATIVE MODELS OF DYSREGULATED BEHAVIOR. Such models provide formal content to otherwise ambiguous psychological constructs and thereby guide the identification of neural structures and functional relations that underlie addiction.

• THE ROLE OF ENVIRONMENTAL FACTORS IN RELAPSE. It would be difficult to overstate the importance of conditioning principles in relapse. We know that events paired with drug reinforcers occasion drug use and cravings but we have a poorer appreciation of how to exploit this understanding to program, for example, the generalization from treatment to community and domestic environments or to apply associative processes in predicting or preventing relapse.

• TRANSLATIONAL STUDIES TO IMPROVE TREATMENT. Direct application of behavioral economic principles can be found, for example, in the emergence of contingency management and other behaviorally based approaches to manage, treat, and prevent addictive disorders.

• CONTINUED SUPPORT FOR RESEARCH ON ADDICTIVE DISORDERS IN GENERAL. This includes gambling and other addictive disorders that do not involve drugs. It is our understanding that this support will continue, but we feel that this is so important that we wished to strongly endorse it.

By clearly articulating a role for basic behavioral research, NISUAD can become a leader in basic and translational behavioral science. Our understanding of conditioning processes advanced significantly because of the support of NIDA and NIAAA. With the formation of NISUAD these advances can continue to grow.

DESCRIPTION OF ABAI

This comment is submitted by the Association for Behavior Analysis International (ABAI), a scientific organization of over 6400 members who conduct basic and translational behavioral research with humans as well as nonhuman species. Since its founding in 1974, its membership has been focused on uncovering and applying basic principles of reinforcement and conditioning, principles that have been of enormous value in understanding addictive disorders.

This simple step will sustain scientists involved in basic and translational studies. Here, we mean developing RFAs, RFPs and other funding opportunities for basic and translational behavioral research, and cultivating program officers and study sections with expertise in behavioral science. Without such an institutional commitment behavioral research will be in danger. In fact, the diminished support for basic behavioral research by NSF and NIMH is a serious threat to the sustainability of a field that has made important theoretical, methodological, and translational contributions to the investigation of addiction. This presents an opportunity for NISUAD to become a major influence. NIDA and NIAAA benefited enormously by the research conducted by behavioral scientists, and so will NISUAD if it supports basic research.

2. IDENTIFY BASIC AND TRANSLATIONAL BEHAVIORAL RESEARCH AS A PRIORITY.

This will improve our understanding of all stages of the addiction cycle and in the design of intervention strategies to break this cycle. The development of a substance abuse disorder, its prevention and treatment, and the sustainability of the benefits of treatment are all, in essence, behavioral problems. Any public health effort aimed at the treatment or prevention of substance abuse will include behavioral principles as a central component. Yet our understanding of these principles, and their translation, remains incomplete.

A second critical area is in continued research support and infrastructural development in integrative bioinformatics. The needs of behavioral neuroscientists are unique and the complexity, depth and scope of investigation in neuroscience merits special consideration of reference and application ontologies for conditional analysis of the role of biological entities in neurobehavioral processes, anatomical atlases, translational and comparative genomics, and advanced modeling for data integration. None of this can happen without adequate financial and cultural support for data sharing, data repository construction and interoperable, user-friendly and stable interfaces for investigators with diverse research applications. The impact of such systems is to maximize return on research investment by enabling discoveries beyond those for which data were initially generated, and by reducing the time and effort for integration across findings through computation.

My primary concern is that any potential sharing of resources reflect the disproportionately high burden of alcohol use disorders on individuals, families, and communities.

It's irrational to let personalities or politics, rather than empirical evidence of costs, drive funding allocation.

Engaging the medical community in prevention and treatment of drug addiction and alcoholism: This too is critical insofar as most medical practitioners do not feel competent to recognize or intervene with addicted patients, which delays treatment and denies patients the benefits of early intervention. Encouraging patient recognition and utilization of effective substance abuse treatments: The focus on involving industry will only be successful if patients recognize the potential utility of available treatments. There currently exists a societal bias against medical treatment of addictions that will require thoughtful and science-based efforts to educate and interest patients and physicians in addiction treatments. Alleviating the translational bottleneck for treatments to move from the bench to the bedside to the community: There is, at present, little incentive to translate treatments. Thus, in the face of resistance borne of traditional views of recovery, translation is minimal. A concerted effort that incorporates both alcohol and drug addiction research is needed to improve this situation. Improving prevention efforts by developing a better understanding of the patterns and trajectories of drugs of abuse and their influence on brain development: Longitudinal studies that provide genetic, neuroimaging, and psychosocial data to address these issues are limited and the joint effort of alcohol and drug abuse researchers is needed to remedy this situation.

Targeting efforts to prevent substance abuse in adolescents and young-adults: Science-based policy is seriously lacking.

Developing strategies to enhance stakeholder interest in developing medications to treat various addictions, including nicotine and alcohol

Engaging the medical community in prevention and treatment of drug addiction and alcoholism

Encouraging patient recognition and utilization of effective substance abuse treatments

Improving prevention efforts by developing a better understanding of the patterns and trajectories of drugs of abuse and their influence on brain development

2. What would be the financial cost of this structural re-organization?

3. What would be the impact of the re-organization on ongoing research programs, including those on FASD?

4. Should the scope of the new institute be broader than addiction?

Additionally, because alcohol is a legal beverage, an agenda associated with illicit drugs may distract from the larger public health burden associated with alcohol use.

Importantly, the scientific directions for the new institute should not be based on the assumption of a common etiology/neuropathway for all the included disorders (e.g., see attached manuscript by Oscar-Berman & Marinkovic). Differences in drug action suggest many distinctive etiologies, processes, and consequences, along with multiple targets for effective treatments and medications.

Moreover, behavioral, developmental, and social science research, along with epidemiology, prevention, treatment (medical and behavioral), and policy research, must be emphasized equally with bioscience in the new institute if public health advances are to be made; that is, the new institute should not be exclusively devoted to neuroscience.

For a new institute on substance use and addiction, the research portfolio must include health promotion. Alcohol is unique in many ways with its health promoting effects at low doses (in the majority of the adult population) and danger with excessive use. Educational programs (and their evaluation) are critical for the youth and public at large.

NIAAA has utilized a “systems biology” approach to its efforts addressing the impact of alcohol on the entire body and organ systems. This has served research well since alcohol has such a wide array of effects on the organism. There has been some suggestion about removing certain areas of alcohol research (prenatal alcohol exposure and end organ damage as examples) to other institutes. This type of isolation would have devastating effects on these areas of research. It is critical that all aspects of alcohol research remain within this new institute. Fetal alcohol research, as an example, needs to be within an institute that focuses its research program on how alcohol affects not only brain but various organ systems, immune function, behavior, etc.

The APA is a long-time supporter of the critical research undertaken at both the National Institute on Alcoholism and Alcohol Abuse and the National Institute on Drug Abuse. We will continue to be a strong advocate for NIH’s much-needed resources to prevent, identify and treat substance use disorders and their impact on co-occurring mental illnesses. The APA stands ready to work with NIH as discussions on the proposed NISUAD move forward.

For a new institute on substance use and addiction, the research portfolio must include health promotion. Alcohol is unique in many ways with its health promoting effects at low doses (in the majority of the adult population) and danger with excessive use. Educational programs (and their evaluation) are critical for the youth and public at large.

NIAAA has utilized a “systems biology” approach to its efforts addressing the impact of alcohol on the entire body and organ systems. This has served research well since alcohol has such a wide array of effects on the organism. There has been some suggestion about removing certain areas of alcohol research (prenatal alcohol exposure and end organ damage as examples) to other institutes. This type of isolation would have devastating effects on these areas of research. It is critical that all aspects of alcohol research remain within this new institute. Fetal alcohol research, as an example, needs to be within an institute that focuses its research program on how alcohol affects not only brain but various organ systems, immune function, behavior, etc.

2. In my view, developmental, behavioral, social science, epidemiology, prevent, treatment, and policy research must have at least the same emphasis as does bioscience in the new Institute. The social science advances in understanding etiology, the development of effective prevention programs, and vastly improved treatment simply must continue. Within the traditional biological health sciences, psychologists and other behavioral professionals have become increasingly central. In part this is because causes of diseases are recognized as combinations of the behavioral and the biological, and in part because, in the end, any treatment required adherence/compliance, which is a behavioral matter.

3. The public health burden is roughly 1/3 due to alcohol, 1/3 due to tobacco, and 1/3 due to illegal drugs or misused prescription drugs. The new Institute has the opportunity to allocate resources in a way that is consistent with the public health burden. It is crucial that funds be allocated to reflect the nature of the burdens to society.

4. A crucial part of my research involves the identification of both common and distinct etiological factors across addictive behaviors: I focus primarily on alcohol, tobacco, and eating disorders. It has been my professional experience that scientists are often less aware of common etiological factors across disorders than they should be, with the result that, for example, tobacco researchers reinvent the wheel that had already been invented by alcohol researchers. The new Institute has the opportunity to facilitate growth in understanding each addictive behavior, by encouraging the kind of synergy across disorders as RSA has cultivated within the alcohol research world.

The public health burden is roughly 1/3 due to alcohol, 1/3 due to tobacco, and 1/3 due to illegal drugs or misused prescription drugs. The new Institute has the opportunity to allocate resources in a way that is consistent with the public health burden. It is crucial that funds be allocated to reflect the nature of the burdens to society.

Another thing that has become clear over the decades I have studied alcohol and drug use is that a multidisciplinary approach that takes into account individual and environmental factors is critical to understand the nature and course of substance use disorders. There is a lot to be gained by examining multiple perspectives from behavioral and social science, genetics, neuroscience, epidemiology, prevention and treatment science, and policy research. Therefore, it is important to continue to fund research in all of these areas and not to focus only on neuroscience or biology.

Finally, it is clear that addiction can be prevented by modifying behavioral and environmental risk factors and enhancing protective factors. Therefore, the new institute must continue to support prevention research including etiology, development, implementation and dissemination of interventions, and evaluation of programs. One way to ensure continued funding of this research is to maintain a division dedicated to prevention. Equally important, of course, is the development and evaluation of new treatment approaches for those who develop addictive disorders. Thus, continued funding of both prevention and treatment belongs in the portfolio of an institute dedicated to studying addictive disorders.

Increase funding for alcohol research independent of other drug use research.

Develop a Prevention Branch in the new institute.

Include research on the development of cigarette use and prevention and treatment of tobacco addiction in the new institute's portfolio.

Effects on the Public: the public may perceive that all addictions are alike, and adopt a least common denominator of concern to all.

Effects on the Scientists: Research on Alcoholism is, by comparison to research on other chemicals of abuse, broad and deep in its scope, addresses an illness adversely affecting more Americans than all other chemicals except nicotine (the current institutes collaborate on nicotine and alcohol quite effectively), underfunded by a substantial sum, and quite advanced in its attention to genetic and environmental influences and its systems approach to organ-system interaction. The scientific depth of perspective and interdisciplinary collaboration (valuable synergy) will be lost by the proposed homgenization.

BUDGET (The approach so far will cost serious money).

SCOPE of research.

LOSS OF SYNERGY resulting from depth of perspective and interdisciplinary collaboration earned by one institute focusing on a ubiquitous illness for a long time.

This one area that has not been sufficiently explored in the USA. There are many misconceptions about alcohol drinking as well as alcohol drinking behaviors that hindered the productive research on the beneficial aspects of moderate alcohol on, for example, the cardiovascular system. Many clinical indicatives in Europe have shown that moderate alcohol, improves the survival rate after myocardial ischemia. Others point to the positive clinical evaluation of the cardiac function and stroke co-morbidity of moderate alcoholic versus non-alcoholic as well as versus heavy alcohol drinkers. It is time for NIAAA to take the lead into that direction and put emphasis on the basic and translational research that allows expansion of our knowledge base on the mechanisms related to the beneficial effects on health of moderate alcohol. It should be taken into consideration that we are definitely not advocating to encourage alcohol drinking patterns that leads to addiction or dysfunction, which are different from moderate alcohol consumption.

(1) Drug consumption, risky sex, overeating, and gambling are all behaviors. NIH must recognize that both biology AND behavior are important in the science of addiction, and increase the emphasis on behavioral and social science. (2) It is critical to maintain an emphasis on prevention research in the new institute. Prevention has been scientifically demonstrated to be both effective and cost-effective. The value and potential of prevention science has been carefully reviewed in the 2009 IOM report, Preventing Mental, Emotional, and Behavioral Disorders Among Young People. (3) It follows that it is critical to establish a prominent prevention research branch in the new institute, and to provide it with a budget that equals or exceeds the total resources currently devoted to prevention in the various institute branches that will be merged. (4) NIDA, NIAAA, and NCI have all funded research aimed at developing new quantitative methods, i.e., research design and statistical analysis, for behavioral research applications. This has helped move the field forward tremendously. The new institute must maintain this program.

Critical Issues:

Qualify the differences among addiction to smoking, tobacco, and nicotine. We need a better understanding of whether dependence on nicotine is a true addiction, or whether nicotine is being used for self-medication of underlying conditions.

Explore whether the practice of Tobacco Harm Reduction—replacing smoking with nicotine from less hazardous sources—will increase success rates for those with psychiatric and substance abuse disorders.

Evaluate where products fall on the risk continuum and convey this information to tobacco users, so that they can make informed choices.

Gain a better understanding of dependency and/or addiction related to tobacco use: One critical issue that has not been addressed is to qualify the differences among addiction to smoking, tobacco, and nicotine. Some research suggests that smoking addiction is much more complex than chemical dependency on nicotine. In the first place, smoke may contain additional chemicals that make it more addictive than non-combusted tobacco and more addictive than nicotine itself. In the second place, there is reason to believe that people may become addicted to the motions of the act of smoking and to the visual manifestation of smoke.

Many people use nicotine when they are struggling to remain alert and attentive, or when they are striving for emotional equilibrium. We need a better understanding of whether dependence on nicotine is a true addiction or whether, when separated from other elements in smoke, nicotine is no more addictive than caffeine, which is often employed for similar purposes. We also need to take into account that some people use nicotine as self-medication for underlying conditions.

Nicotine consumption seems to plateau after users find a "level" that is comfortable for them--this is unlike "true addiction" that reinforces itself by constantly requiring the user to increase the dosage to achieve the desired euphoria that is rarely, if ever, associated with nicotine. Many people are able to temporarily quit smoking with NRT, but the success rate falls to less than 10% after just 6 months and continues to fall down to less than 2% after 20 months, well after treatment has ended. Since all indications are that all nicotine will have been metabolized and have left the body within 30 days, relapse after this time is another indicator that it is not a "true addiction" to nicotine, but far more likely to be treating an underlying cognitive deficit that benefits from natural neuro-stimulant alkaloids like nicotine or caffeine.

Increase success rates for those with co-morbid conditions: Selecting the most appropriate treatment is another critical issue because more than 40% of smokers have an active psychiatric or substance abuse disorder. Prescription drugs that target neuronal receptors may exacerbate psychiatric problems. Current and Lifetime Major Depressive Disorder are associated with a lower likelihood of quitting smoking and Current Major Depressive Disorder is associated with greater likelihood of smoking relapse. Nicotine has been shown to reduce symptoms of attention deficit and mood impairments. We need to explore whether the practice of Tobacco Harm Reduction—replacing smoking with nicotine from less hazardous sources—will increase success rates for those with psychiatric and substance abuse disorders.

Evaluate products for comparative risk: The Family Smoking Prevention and Tobacco Control Act has introduced the concept of modified exposure tobacco products, as well as modified risk products. We need to evaluate where products fall on the risk continuum and convey this information to tobacco users. Helping those with co-morbid conditions to transfer their dependence from smoking to less hazardous products may prove to be the most effective treatment method.

Another issue of considerable importance is the notion that there is a common etiology for all addictive disorders. I have experience researching multiple addictive drugs including ethanol, cocaine, methamphetamine, and morphine, among others. My research has focused on genetic factors that influence sensitivity to these various drugs of abuse and risk for dependence. My investigations clearly show that, although there is some overlap in brain circuitry, different genetic factors impact risk across drugs and the importance of particular biological processes varies as well. There are highly significant differences in drug actions within the brain, so it should not be surprising that there are distinct processes involved and that it is extremely unlikely to identify treatments that are highly effective for all addictive disorders. Support for this opinion is scientifically based. For example, there have been decades of focus on dopamine systems and evidence for the involvement of dopamine circuitry across many addictions, yet dopaminergic drugs have not been effective global treatments for addiction disorders.

Finally, there is the impression that the attention paid to research into alcohol-related problems has been overshadowed by that paid to research into problems associated with illicit drug use. This should not continue to be the case. Alcohol use poses a highly significant burden to society and should be appropriately integrated into the new Institute so that it receives at least equal if not greater attention as do illicit drugs. The health burden of alcohol use to society is greater than that of any of the illicit drugs.

Francis S. Collins, M.D., Ph.D Director National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892

Dear Dr. Collins,

The American Society of Addiction Medicine (ASAM) is pleased to have the opportunity to offer input into the Scientific Strategic Plan for the proposed National Institute of Substance Use and Addiction Disorders (NISUAD); in particular, we hope our comments support the maintenance of research regarding the medical complications of addiction.

ASAM represents nearly 3000 physicians who specialize in the treatment of addiction; many of whom work in research or academic settings that rely on the addiction research outcomes and/or funding provided by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcoholism and Alcohol Abuse (NIAAA). In fact, ASAM members in research and clinical practice alike have benefited from and implemented the advancements in addiction treatment-related science provided by NIDA and NIAAA. Furthermore, ASAM is grateful for the ongoing collaborations between these Institutes and ASAM to advance the science and practice of addiction medicine. We hope the following comments are useful to you as you consider this merger and the realignment of their respective portfolios.

It is our understanding that while the Scientific Strategic Plan will integrate various elements of NIDA’s and NIAAA’s research portfolios; other elements of these portfolios may be moved to other centers within the National Institutes of Health and/or eliminated altogether. ASAM is particularly concerned that the research and science regarding the medical complications of addiction like liver disease, fetal alcohol syndrome, and hepatitis, may be redistributed to the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development, or the National Institute of Allergy and Infectious Diseases, respectively, and lose the priority status they held within the addiction institutes. Moreover, these broader disease institutes may not be as sensitive to the co-morbid relationship of these disease states and addiction as are NIDA and NIAAA. Should this element of addiction research and associated funding fade within a reorganized NIH, addiction treatment providers, their patients and the public will suffer.

The members of the American Society of Addiction Medicine have been both beneficiaries and supporters of the life-changing research put forward by NIDA and NIAAA. We look forward to future collaborations with a new National Institute of Substance Use and Addiction Disorders that advances the current research portfolios of the NIDA and NIAAA and, consequently, the implementation of the NISUAD’s contributions in addiction treatment settings and training programs nationwide.

An effort to understand how environmental factors (such as social status, dietary habit, exercise/ sport activities, other habits) influence the brain and the susceptibility to drug addiction and other addictive behaviors would not only help prevention but may also help developing ways to intervene with young developing brains at the initial stage of addiction.

An effort to pursue off-label usage of FDA-approved drugs for addiction would greatly benefit the public. It is important to note that epidemiological data may not be available for addiction (e.g., whether addicts taking antihypertensives have lower relapse rate) because addicts tend to be young and also not willing to pay attention to their health (blood pressure, blood glucose level, etc.) and seek medical service. Furthermore, pharmaceutical companies may not be interested if the patent has expired for that drug.

Investigating how pharmacotherapy interacts with psychotherapy would touch the core of drug addiction, which is driven by drug-induced learning and memory processes.

Promising new medications are emerging for alcohol dependence - are they effective for other dependencies? Genetics of alcohol action in humans and animals are rapidly emerging - do the same gene influence sensitivity or dependence on other drugs? An integrated systems biology approach is needed which requires study of all organs, not just brain. Organ damage for all drugs must be part of the new institute.

Reorganization of addiction research at NIH must be guided by experts with a wide range of expertise in addiction, including a background in actions of the key drugs, nicotine and alcohol, and a deep appreciation of psychosocial aspects, organ damage, medication development and genetics.

Furthermore, there are fundamental differences in the nature of brain targets of alcohol relative to that other drugs. Alcohol is by far the most pleiotropic drug known to man. As of today, I can recount at least two dozen molecular targets through which pharmacological concentrations are known to directly interact. These include numerous ligand-gated ion channels, numerous G-protein coupled receptors, a variety of kinases, phosphatases, transcription factors, neuroimmune modulators and the list becomes even more extensive every month. It is only by concentrating one's career in this specific drug of abuse, can one adequately review and comment on the work of others.

When these two prior points are taken in combined consideration, I can insure the NIH that combining the portfolios of alcoholism with that of other drugs is a monumental mistake which will promulgate a huge disservice to both arenas. When one further considers that the dollar and medical costs due to alcohol are already woefully under-represented by biomedical research appropriations, I predict that such an administrative move would constitute the death knell for the basic alcohol research and fundamentally reverse the major advances made by myself and my colleagues over the past 20 years.

There is another issue I have as well - concerning the public welfare in general: the disintegration of an institute dedicated to ALL aspects of alcoholism and its abuse will result in serious negative repercussions to those aspects of alcoholism not directly related to brain mechanisms of addiction. For instance, prenatal and perinatal neurotoxicities are endemic to alcoholism and yet separating those components of biomedical research from those related solely to addiction will result in a rift between those very closely related disciplines. I know this for a fact since I first entered the field on a project related to synaptic plasticity deficits due to prenatal exposure and my discoveries directly impacted our understanding of ethanol-NMDA interactions due to direct brain exposure as in abuse. For my work, I received the RSA Young Investigator award. If the proposed unit structure existed then, I doubt that the basic research in the prenatal area would even funded - I am not aware for any adequate representation for funding non-addiction related alcohol effects - this concern applies not only to prenatal effects but also hepatic and other organ system toxicities and related effects of abuse.

2. Poly-drug abuse is common because most individuals abusing illicit drugs also use/abuse alcohol and/or nicotine. Thus, the new institute should strongly encourage research on how alcohol and nicotine contribute to likelihood of relapse to other substances.

3. Much greater emphasis must be placed on understanding genetic differences in the response to alcohol and other drugs and the way those differences contribute to abusive patterns of drug taking and dependence.

4. Animal model research that focuses on processes influencing the maintenance, elimination and relapse of alcohol and drug seeking/taking in animals that are clearly dependent must be encouraged. Many (most?) of the current models of “relapse” (reinstatement) do not involve dependent animals and their relevance to human alcoholism and drug addiction is questionable.

5. Research on the biomedical consequences of alcohol and drug addiction (e.g., liver disease, fetal alcohol syndrome) should NOT be conducted in institutes whose mission does not address research on the causes, treatment and prevention of addiction. These areas of research should be included in the new institute.

6. Greater emphasis should be placed on understanding the patterns of alcohol and drug use in adolescents and young-adults as well as on understanding the neuro-developmental processes that influence the likelihood of developing dependence disorders later in life.

7. Increased effort must be devoted to understanding and removing the barriers to treatment and encouraging health care providers to use treatments that have been found to improve patient outcomes, including medications.

2. Poly-drug abuse is common because most individuals abusing illicit drugs also use/abuse alcohol and/or nicotine. Thus, the new institute should strongly encourage research on how alcohol and nicotine contribute to likelihood of relapse to other substances.

3. Much greater emphasis must be placed on understanding genetic differences in the response to alcohol and other drugs and the way those differences contribute to abusive patterns of drug taking and dependence.

4. Animal model research that focuses on processes influencing the maintenance, elimination and relapse of alcohol and drug seeking/taking in animals that are clearly dependent must be encouraged. Many (most?) of the current models of “relapse” (reinstatement) do not involve dependent animals and their relevance to human alcoholism and drug addiction is questionable.

5. Research on the biomedical consequences of alcohol and drug addiction (e.g., liver disease, fetal alcohol syndrome) should NOT be conducted in institutes whose mission does not address research on the causes, treatment and prevention of addiction. These areas of research should be included in the new institute.

6. Greater emphasis should be placed on understanding the patterns of alcohol and drug use in adolescents and young-adults as well as on understanding the neuro-developmental processes that influence the likelihood of developing dependence disorders later in life.

7. Increased effort must be devoted to understanding and removing the barriers to treatment and encouraging health care providers to use treatments that have been found to improve patient outcomes, including medications.

First, focusing the mission of the new center solely on addiction will restrict the funding rubric to CNS-related consequences of drug exposure. This would represent a true threat to scientific progress because peripheral physiology (endocrine reactions, dynamic organ system alterations, and other physiological processes) are critical moderators of brain function. Not only does peripheral physiology determine the CNS response to drugs of abuse, it may critically determine whether the individual is driven down the addictive path. This will be especially true for alcohol, as alcohol acts through a wide variety of direct and indirect cellular actions throughout the entire body.

Second, many of the premier researchers in this country have argued that addictive processes are in fact a developmental phenomenon. The past decade has seen a tremendous increase in studies demonstrating that the developmental epoch during which individuals are exposed to alcohol and other drugs of abuse is as critical in determining the outcome of drug exposure as the dose of the drug itself. Indeed, both pharmacokinetic and pharmacodynamic properties of the drug are powerfully impacted by stage of development (fetus, newborn, adolescence, adult, aged). To separate addictive processes from organismic development, therefore, would be a significant step in the wrong direction. Overall, I believe the entire dialogue about merging has generated exactly the type of cross-institution collaboration and generating funding ideas/new strategic goals that NIH had hoped to achieve with the merger. This, combine with a targeted series of program announcements and joint funding ventures within the existing NIAAA and NIDA agencies would probably achieve the desired objective without the major disruption to scientific momentum that already exists through NIAAA and NIDA.

HIV, HCV and STIs are all major public health problems that are linked to use of alcohol and other drugs. Accordingly, I am very concerned that HIV, HCV and STIs do not seem to be a focus area of the institute. The other NIH institutes do not seem to be well-suited for addressing issues related to the intersection of alcohol and other drug and HIV, HCV and STIs. If these public health problems are not among the priorities of the new institute, they are likely to be neglected and an important opportunity for reducing morbidity and mortality among alcohol and other drug users will be lost.

The new institute should support research on disorders that are co-morbid with substance use, such as HIV.

The emphasis on prevention that currently exists in NIDA should be maintained at least at the current level in the new institute.

Research to advance quantitative methods has resulted in new approaches that have been very beneficial to the substance use research field. Such research should continue to be supported by the new institute.

Research to advance quantitative methods has resulted in new approaches that have been very beneficial to the substance use research field. Such research should continue to be supported by the new institute.

I feel that the new institute needs to include the following areas of research that are critical for promoting public health. 1) Behavioral and social science research, along with prevention and intervention work, must to supplement the focus on neuroscience. For example, work in epidemiology documents the scope of the problem, work in development sheds light on critical age periods for intervention, and work in prevention provides evidence for effective strategies. These areas of research are essential for addressing substance use among Americans. 2) The predictors and consequences of alcohol use (a legal substance) are different than predictors and consequences of illicit drugs, and this must be understood and acknowledged in the research agenda. 3) A focus on the associations between substance use and HIV is necessary. 4) Research to advance quantitative methods enhances the substantive research we are able to do, and this focus should continue in the new institute.

Policy Research. It is critical that the new institute take into account the importance of policy-relevant research. There is a paucity of current data on many policy interventions and NISUAD has an opportunity to dramatically change that reality. Too often, NIDA and NIAAA have hesitated at the chance to conduct true drug policy analysis, likely because this is not seen as "basic" science more typical of NIH institutes (notable exceptions are recent research into drugged driving and the impacts of "medical" marijuana). Given that drug abuse is a complex bio-behavioral disorder, sharing many -- but not all -- of the attributes of traditional diseases more typically the focus of NIH (like heart disease or cancer), NISAUD cannot afford to overlook this critical area. Practitioners in the field of prevention, treatment, and law enforcement need evaluations on their work in order to refine what they do and make necessary changes in policy, if required. No other entity in the government has the ability to conduct true drug policy analysis in a way that would be taken to scale. It is critical that NISAUD not ignore this area.

Prevention. Prevention is the most cost-effective, yet in many cases the least understood, intervention in the field of drug abuse. It is critical that NISAUD take a leadership role, as NIDA and NIAAA have in the past, in funding and seeing through prevention interventions that go beyond simple school-based programs and focus on environmental factors. Included here would be an increase in type 2 translational research, including studies of the adoption, implementation, and sustainability of tested and effective programs, policies, and practices in communities, services settings, and populations. This research would ensure that existing knowledge results in reductions in the incidence and prevalence of alcohol or drug abuse and addictions.

Drug-Related Crime. Unlike many of the diseases focused on at NIH, drug abuse fuels crime - through the psycho-physiological changes done as a result of drug taking to the market dynamics of illegal and quasi-legal substances. It is no longer possible to ignore this connection and NISAUD should work closely with the National Institute of Justice to evaluate criminal justice system interventions and bring the most successful ones to scale.

HIV/AIDS. Given the nexus between HIV/AIDS and drug use, abuse, and addiction, it is critical that NISAUD continue the work being done by NIDA and NIAAA on HIV/AIDS. This should be done in coordination with other federal entities (ONAP, CDC, OGAC/PEPFAR).

It is said that NIH funds 85% of the world's research in the area, but that research informs perhaps 15% of the world's and the US's spending on drug control.

The great bulk of social costs of illegal drugs in the US are driven by cocaine/crack, heroin, and meth. People under criminal justice supervision (probation, parole, and pretrial release) consume the majority of all three of those substances. The centrality of criminality and the justice system are undeniable.

Furthermore, cost-of-illness studies find that crime-related costs (and also lost productivity) loom large, much larger than health-related costs other than lost productivity from premature death.

The nation's funding mismatch is not sustainable in the long term. No one in this budget climate is going to invest new billions to research drug-related crime, enforcement, markets, production & distribution systems, etc., so achieving balance means either cutting NIH budgets or expanding NIH's scope. Obviously the latter is preferable.

I think the new entity would be particularly vulnerable to a budget cutter's attack that it better serves addiction scientists than the public or the taxpayers if the NIDA culture were to prevail over the NIAAA culture in the new institute.

The good news is that so little is spent on research on justice-related issues that NIH could become a major player in that area with a modest share of its budget.

Diverted pharmaceuticals kill more people than all other illegal drugs combined. NIH has not made that topic a priority.

The drug policy issue of the greatest interest to the largest number of voters pertain to marijuana availability (medical MJ, legalization, decriminalization, etc.). NIH shuns that topic.

There is much worry about translational research -- but not focused, as far as I know, on contingency management.

The explosion of violence in Mexico and Central America are among the most important developments in the field of illegal drugs over the last decade; NIH has nothing in particular to say about it.

There needs to be a balance between public health and "bench" science, and between community & societal level inquiries and those at the individual and cellular level. NIDA has not maintained that balance. I hope the new institute does.

It is critical that the new institute include provision for health research on disorders that are comorbid with substance abuse such as mental health disorders as well as AIDS

The emphasis on prevention and clinical treatment that currently exists in NIDA should be maintained at least at the current level in the new institute.

Research to advance quantitative methods has resulted in new approaches that have been very beneficial to the substance use research field. Such research should continue to be supported by the new institute.

Finally, exposure to teratogenic agents prenatally results in life-long effects, some of which appear only later in life. For example, prenatal alcohol exposure leads to an increased propensity for alcohol and drug use during adolescence and adulthood, effects that are likely related to changes to CNS systems being investigated in the proposed Institute. Focusing on the teratogenic effects of maternal alcohol and drug abuse as a childhood disorder misses some of the devastating effects of prenatal exposure that transpire across the life-span.

In sum, I would argue that the synergies that would be lost by separating prenatal exposure to alcohol and drugs of abuse from the proposed Institute are antithetical to the goals of the Institute, which are to create and foster synergies that can lead improved public health related to substance use and abuse.

My clinical and research experience tells me that medical and psychiatric co-morbidities associated with addiction should be a part of the new institute’s research portfolio. Alcohol and drug use play a key role in the transmission of HIV and hepatitis. Drug injection has fueled the spread of HIV during the epidemic. Hepatitis C infection will eclipse HIV infection as a cause of morbidity and mortality and is highly prevalent in populations of drug injectors. Discovering effective approaches to identify and treat these infections among the drug addicted is of great significance to the public health. Furthermore, drug injectors have played an important role in the spread of HIV to the non-drug using population through sexual transmission. Thus, research regarding prevention strategies of sexual transmission is also critical to public health. Drug addicted patients with these and other medical co-morbidities are often unable to access effective medical care. Services research to identify and assess service delivery models for these conditions is also an important area that should remain in the new institute. This is particularly critical now in the era of health care reform and of cost constraints. Psychiatric illness is a second area of great importance to the addiction research portfolio. Psychiatric disorders are often mimicked by addiction and therefore research regarding differential diagnosis is of import. Depression, anxiety disorders, and post-traumatic stress disorder are prevalent among individuals seeking addiction treatment and effective approaches to treatment and service delivery are needed to improve patient outcomes. Individuals with severe and persistent mental illness, such as schizophrenia, often misuse substances creating adherence problems and illness exacerbation. The new institute should include clinical and services research to address psychiatric co-morbidity in its portfolio.

The new institute should support research on conditions that are co-morbid with substance use, such as HIV, and mental health.

The emphasis on prevention that currently exists in NIDA should be maintained at least at the current level in the new institute.

Research to advance quantitative methods has resulted in new approaches that have benefited substance-use research. The new institute should continue to support studies in quantitative methods.

1. Susceptibility to addiction is greatest from early adolescence through the mid 20s, a time when the brain is still developing. The study of addiction depends crucially on understanding how alcohol affects the developing nervous system. Brain development begins during embryogenesis and does not cease until the third decade of life. Much of NIAAA's FASD portfolio focuses on the effects of alcohol on the developing nervous system. Alcohol interacts with many of the same molecular targets during prenatal and early postnatal brain development as it does in the developing adolescent and mature nervous systems. My own studies on the effects of alcohol on the L1 cell adhesion molecule illustrate this point. L1-mediated cell adhesion is inhibited by alcohol. L1 is critical for development; however, it is also expressed in adulthood, where it influences learning and memory. There is no scientific rationale for dividing the NIAAA brain research portfolio at any arbitrary point in the 3-decade timespan of human development. Therefore, all research on alcohol's effects on the developing nervous system should be coordinated and funded by a single institute.

2. Prenatal alcohol exposure permanently alters the structure and function of neurotransmitter pathways that mediate alcohol addiction. Children exposed to alcohol in utero are at increased risk for developing alcohol addiction. The comprehensive study of alcohol abuse and alcoholism requires the coordinated investigation of all factors that predispose to these disorders, including prenatal alcohol exposure. Therefore, preclinical and clinical studies of FASD should be an important part of the portfolio of an institute on addictions.

3. FASD is the single most important preventable cause of developmental disabilities. By far the most crucial strategy for preventing FASD is the prevention of drinking in women who are pregnant or trying to conceive. The defining face and brain abnormalities of fetal alcohol syndrome result from alcohol exposure during the third to fourth week of pregnancy, a time when most women do not know that they are pregnant. Hence, the prevention of FASD requires a concerted effort to reduce binge drinking in all women of childbearing age. Unfortunately, binge drinking is common, particularly in women in their late teens and early twenties. A broad array of clinical, psychosocial, and policy research has been directed at reducing drinking in this vulnerable population. This prevention research needs to be coordinated to address the specific challenge of reducing binge drinking in women of childbearing age. Therefore, preventing the major public health burden of FASD will depend critically on the inclusion of all FASD research within the portfolio of an institute on addictions.

1. Improving prevention efforts by developing a better understanding of the patterns and trajectories of drugs of abuse and their influence on brain development;

2. Engaging the medical community in prevention and treatment of drug addiction and alcoholism;

3. Targeting efforts to prevent substance abuse in adolescents and young-adults;

4. Understanding the implications of policy changes on substance use patterns and trajectories, especially in youth

I think the mission of the proposed National Institute on Substance Use and Addictive Disorders’ should include targeting the spread of HIV among substance users and reducing the spread of HIV among HIV-positive substance users by enhanced adherence to HIV-suppressing treatment. There are three main reasons to house these HIV-reduction missions in the new addiction agency:

1) Interventions to reduce risk behavior and reduce the spread of HIV require knowledge of substance-using populations, knowledge that will be consolidated within the National Institute on Substance Use and Addictive Disorders.

2) Substance using populations have distinct neurobiological, behavioral and psychological challenges that require interventions tailored to them. Interventions focused on more accessible populations may not be effective in substance users and fail to address this large population that harbors and/or spreads HIV.

3) The integration of HIV risk-reduction into addiction treatment has been facilitated by having HIV risk-reduction part of the mission of NIDA and NIAAA. This has manifested itself in the inclusion of risk-reduction components in standard treatments (e.g. CBT for cocaine use, opioid maintenance), and dissemination of HIV risk-reduction testing and interventions by NIDA and NIAAA. This synergy has been good for HIV risk-reduction and for public health in general.

It is not clear how the public health imperative of preventing the spread of HIV by and among drug users will be carried out if it is not housed in the Addictive Disorders’ agency. Making HIV risk-reduction the mission of another agency would divorce the mission from the population being targeted.

1. Much of NIAAA's FASD portfolio focuses on the effects of alcohol on the developing nervous system. Alcohol interacts with many of the same molecular targets during prenatal and early postnatal brain development as it does in the developing adolescent and mature nervous systems. There is no scientific rationale for dividing the NIAAA brain research portfolio at any arbitrary point in the 3-decade timespan of human development. Therefore, all research on alcohol's effects on the developing nervous system should be coordinated and funded by a single institute.

2. Prenatal alcohol exposure permanently alters the structure and function of neurotransmitter pathways that mediate alcohol addiction. Children exposed to alcohol in utero are at increased risk for developing alcohol addiction. The comprehensive study of alcohol abuse and alcoholism requires the coordinated investigation of all factors that predispose to these disorders, including prenatal alcohol exposure. Therefore, preclinical and clinical studies of FASD should be an important part of the portfolio of an institute on addictions.

I am practicing physician specializing in addiction psychiatry with 30 years experience in the inpatient and outpatient treatment of addiction and dual psychiatric diagnosis disorders. I also work in a NIAAA funded Alcohol Research Center (PI George Koob) and as part of a research group (PI Cindy Ehlers) at The Scripps Research Institute in La Jolla, CA, which receives NIAAA and NIDA grant funding for projects investigating risk and protective factors for alcohol and drug use and addiction in Native American and Mexican American participants. I am a Co-PI in the Research Translation/Information Dissemination Component of The Scripps Research Institute Alcohol Research Center. One of the studies of the Translation Component is to assess a community outreach program to the immigrant Mexican American community in the border areas of San Diego County. I feel I have some useful experience in how valuable education/translational outreach can be in these communities.

I am in concurrence with the preliminary list of potential scientific opportunities and public health needs not sufficiently addressed within the current NIH structure, particularly those relating to substance use and use disorders in adolescents and young adults. Since substance use and addiction often begin in adolescence and young adulthood, assessing effective public policy and prevention strategies aimed at those age groups should be an important goal of the new institute.

To the strategic list, I would add the important scientific opportunity of genetic investigations in identifying risk factors, sites for potential psychopharmacologic intervention, and for monitoring treatment outcome in substance use and use disorders. The new institute should be on the forefront of investigating new genetic technologies, which will become increasingly important in all areas of medicine and public health. I believe that the use of basic science to understand risk factors, physiologic effects, and toxicity of alcohol and drugs should continue as the central aim of the new IC. An important challenge for the new IC, as I see it, will increasingly be that of translation of basic scientific advances not only to the bedside, but also to the community.

Translation to the community should involve sustained attention to the general U.S. population but also to involving minority communities in education and outreach and in the research enterprise itself. Community based participatory research should be a goal of the new IC not only with the aim of studying substance use and use disorders in minority communities but in training young minority researchers in the field.

As a rough rule, I believe that funding should be allocated in the new institute in a way that reflects the public health costs of substance use and addiction.

Thank you for this opportunity to contribute my thoughts on potential scientific opportunities and public health needs to be addressed in the strategic plan for the new institute.

The effects of prenatal alcohol exposure begin prenatally and are life long, they include long term physical, neurochemical, neuroanatomical, and psychological changes. These changes put the affected individual at risk for many secondary outcomes, including but not limited to their own substance use and abuse. This give FAS/FASD research a unique opportunity to identify individuals at risk for substance use very early in life. Early identification and intervention of people with FASD can reduce this risk. NIAAA has utilized a systems biology approach to alcohol and FAS/FASD is a model of this approach; prenatal alcohol exposure affects multiple organ systems, including the brain, both before and after birth. Thus, this continued approach must include the effects of alcohol on the fetus and later child development for the reasons stated.

Second, FAS is preventable if we intervene with women at risk for alcohol use in pregnancy. Removing the FAS/FASD portfolio in essence separates the child from the mother and the opportunity for intervention research may be lost.

For these and many other reasons, I urge you not to separate the FAS/FASD portfolio from the rest of the institute.

However, I also have several concerns about the proposed reorganization and research priorities that I would like to respectfully express:

First, most of the research priorities for improving treatment and prevention for addictions appear to have an exclusive medical/biological focus. There is very little emphasis on behavioral interventions and prevention. And yet, most of the available research indicates that even when effective pharmaceuticals have been developed to treat various mental health conditions such as depression and including addiction, they work best when accompanied by behavioral interventions. Additionally, despite considerable effort over the past 20 years and groundbreaking studies of the neurobiology of addictive conditions, the development of effective pharmaceutical treatments for many such conditions has remained elusive. In these instances, our best and still frontline treatments remain behavioral interventions. Accordingly, I believe the priorities should be amended to include a comparable emphasis on improving the science behind developing more effective behavioral interventions for addictions including prevention at the individual and community levels and studying the optimum way in which behavioral and medical interventions can best be combined.

Second, much of my own work has focused on studying conditions that commonly co-occur with substance misuse such as mental health disorders as well as chronic health conditions and infectious diseases. The link between HIV/AIDS and substance misuse is particularly well established. In this last regard NIDA has shown clear and effective leadership supporting much productive research since the beginnings of the AIDS epidemic. As a result of the considerable efforts at NIDA, effective and important prevention and treatment interventions have been developed to address HIV risk among substance abusers and we now have a very clear understanding of how these two issues intersect.

It is unclear under the reorganization plan, what will happen to this important portfolio of NIDA research studies. My broader concern is that the focus on co-occurring addictive disorders, while laudable, might come at the expense of a loss of focus on non-addiction disorders that commonly co-occur with substance misuse. This loss would be especially unfortunate given the recent trend in the medical and health care communities towards promoting primary care as a gateway for receiving health-related services for multiple conditions via mechanisms such as "medical homes". I believe we need to continue the strong tradition of NIDA-led studies on the co-occurrence of and treatment for addictions and other mental health and health conditions, particularly HIV/AIDS. Therefore, I strongly urge NIH to explicitly retain HIV/AIDS and co-occurring mental health and health conditions under the purview of the newly reorganized institute for addictions studies and to make such studies one of the identified priorities for the newly organized institute.

I recommend that this area should include language that specifically emphasizes study of HIV/AIDS as a “certain disease” in addition to cancers. Unique and significant associations with substance use and HIV/AIDS are noted in the United States. Two separate attributable risk analyses, using HIV seroconversion end-points within two independent cohort studies show that between 28% (Koblin, 2006) and 33% (Ostrow, 2009) of all HIV seroconversions among MSM can be attributed to non-injection substance use. Recent data from HPTN shows that among Black MSM (a group with high background HIV prevalence and incidence), alcohol use with 2 hours of a sexual event is a multivariate predictor of HIV transmission behavior (Penniman Dyer, 2012). There is a compelling and significant need for this combined institute to emphasize study of substance use (alcohol and other drugs, injection and non-injection) and its linkages to HIV/AIDS (both in terms of treatment and prevention), especially in groups of substance users who face multiple disparities due to poverty, race/ethnicity, and other forms of stigma and injustice.

This is an important area as pharma has little incentive to sponsor medication development for drug dependence. Drug dependent patients often are un- or under-insured. This situation limits the ability to sell drugs and make a profit for drugs that ultimately are shown efficacious for treating drug dependence. The area listed that emphasizes recruiting pharma to develop novel medications is important, but the lack of a market that could support profits sufficient to sustain such interests (in the same manner as drugs for other psychiatric conditions) presents obvious barriers for enthusiasm to companies that might otherwise consider drug development for substance dependence.

This situation puts government in the role of the position of last resort for guiding drug development for addictive disorders and emphasizes the need to increase investments in the area of encouraging companies to work in private-public partnerships to address treatment of addictions.

As an another example, it was clear from clinical case studies that genetic factors played a role in the etiology of fetal alcohol spectrum disorders (FASD), but what these factors were was unknown. Using animal model systems and rodents bred for differential sensitivity to alcohol, we were able to show how both metabolic influences and differences in functional tolerance impacted the outcome from prenatal alcohol exposure. The selected lines and the protocols used for these studies resulted from research unrelated to developmental alcohol exposure. For that matter, the protocols for the animal model systems that clearly demonstrated that alcohol was a teratogen were developed to study mechanisms of alcohol-induced liver and other organ toxicity, withdrawal, and tolerance. I am not implying that the research that we did would not have happened if I was not funded by the NIAAA, but it is clear that the research would have been slowed and hampered if I had not been exposed to those model systems through my involvement with the NIAAA. Furthermore, this research clearly showed that the maternal genotype was critically important in determining the outcome from prenatal alcohol exposure, yet moving developmental alcohol exposure to another institute would separate the connection between the mother and the offspring. Maternal drinking would be studied in one institute, while the consequences of that drinking would be studied in another. That makes little sense. I guess it could be argued that perhaps maternal drinking would also be studied in the institute where developmental alcohol exposure would move to, but that would disconnect the drinking of a woman who happened to be pregnant from the drinking of other women, which again makes no sense to me.

It is very clear that the developmental alcohol exposure field has benefited from the close contact with alcohol research in general. Much of what we learned about mechanisms responsible for alcohol-induced teratogenesis and prevention of FASD has resulted from close ties to the alcohol research community in general. Even relatively simple principles such as drink size and how this influences consumption and recall of that consumption, how to address asking women about their drinking, assessing the influence of being raised in a family where alcohol is used and abused, and the nutritional aspects of alcohol consumption that influences outcomes, all find their roots in the broader questions asked by alcohol researchers, not those only focusing on developmental exposure. Separating those interested in the outcomes from prenatal exposure from those studying broader issues related to alcohol use and abuse will only impede scientific progress.

As a final example, individuals exposed to alcohol in utero are at an increased risk for alcohol abuse latter in life. The role of genetics versus teratogenic influences is still unclear in this regard, but once again the research would be better served by keeping the research on developmental alcohol exposure in the same institute where alcohol use and abuse are studied in general.

I have been involved in the field of teratology since the mid 1970’s, and have studied other exposures besides alcohol. Within the NIH, the study of teratogens goes on in many institutes. Those causing oral-facial consequences are studied in NIDCR, yet many of these teratogens also have CNS consequences. The study of ADHD, which might be the closest analog to FASD in terms of behavioral outcomes, is primarily funded by NIMH. The study of autism goes on in multiple institutes, including NIMH, NICHD, NIDCD, and NIEHS. The study of environmental teratogens is done at NIEHS. Yet the proposal is to move research on the consequence of prenatal alcohol and drug exposure from an institute devoted to alcohol and substance use to an institute such as NICHD. The logic fails me, as I do not see the scientific benefit of separating the study of the agent from the consequences of exposure to that agent.

In summary, the current arrangement where research on FASD is funded by the same institute studying alcohol use and abuse in general simply makes the most sense in terms of scientific benefits and “bang for the buck.” The research and synergies that have been established by having this work funded primarily by the NIAAA have moved our knowledge about the consequences of prenatal alcohol exposure from next to nothing to where FASD is being considered for inclusion in the DSM in less than 40 years. The strides in this field have been tremendous and the current model of funding FASD research in the same institute studying the etiological cause of these disorders had been exemplary. I urge you for the sake of the public health to keep the current model.

1. NIH Staff: Public Health Opportunities (PP slide 10). The strategic plan for the new institute should reflect the awareness and commitment of the NIH to address the burden of illness in the general population associated with the use and addiction to alcohol, tobacco, illicit drugs and prescription drugs used without or beyond the limits of a prescription. Data were published recently by Grant, Dawson and Moss (2011). Importantly, among US adults 18 years of age and older, the estimated numbers of current users for alcohol, tobacco, and illicit drugs are 136, 57 and 12.2 million, respectively. For users of illicit drugs, cannabis accounts for 8.5 million or 70 percent of the total of 12.2 million. For abuse of prescription medications, it is 8.3 million. However, the estimated number of current addicted users of alcohol, tobacco and illicit drugs are 7.9, 26.5, and 1.2 million, respectively. The numbers clearly indicate that tobacco, heroin, cocaine and amphetamines are more addictive than are alcohol and other psychotropic substances. However, owing to the relatively low numbers of users in the general population, the numbers of illicit drug users are individually very low, with cannabis accounting for more than 50 percent (0.67 million) of the 1.2 million total.

2. Understanding the mechanisms by which alcohol and other drugs of abuse increase risk for certain diseases e.g. cancer (PP slide 8), I would like to point out that alcohol is unique among all drugs in that its metabolism and its immediate metabolic products directly lead to, not just are contributory, to certain end organ diseases. Most notable among these are alcohol addiction (brain), alcoholic liver disease (liver), fetal alcohol syndrome (fetus), and cancers of the upper aerodigestive tract. Alcohol is unique in that its pathway of metabolism, which accounts for more than 95 percent of its elimination from the body, is by way of its oxidation first to acetaldehyde, then to acetate and finally to carbon dioxide and water, using the metabolic pathways common to those for carbohydrates and fats in the generation of ATP and energy. Thus, alcohol consumption leads also to the generation of energy (98 Kcals per standard drink containing 14g ethanol), which is contributory (increasing the risk) for other diseases such as those associated with nutritional imbalance (including obesity) and those that have multiple identified and yet unidentified genetic and environmental/lifestyle risk factors. Alcohol is a sedative/hypnotic substance with low efficacy. Millimolar amounts are required for its CNS effects. By contrast, acetaldehyde is much more potent, with demonstrated reinforcing effects in micromolar concentrations. Acetate effectively preempts glucose metabolism in the brain and is incorporated directly into glutamate and glycine in the brain. It is possible that acetate can serve as the major source of energy in the brain of a chronic alcoholic; this is a novel research initiative worthy of exploration.

As provided in Dr. Tabak’s response to Sherry Deren (Q/A p12), knowing that “a substance has a direct impact on an end stage organ, you could make the argument that it would make sense (to keep it in the new institute) if that was unique to that specific agent.” In line with this thought process, I would urge keeping alcoholic liver disease, fetal alcohol spectrum disorders and upper aerodigestive cancers together with alcohol addiction in the new institute because of the unique direct impact of alcohol and its immediate metabolites on these disorders.

3. Pharmacokinetic and Pharmacodynamic Interactions Between Alcohol and Other Therapeutic Agents (PP slide 8). I wish to emphasize that is important to do so across the lifespan. Whereas alcohol and drugs do not change, the users and addicted users do. For example, the pharmacokinetics (absorption, distribution and metabolic rate) and the CNS pharmacodynamic effects of alcohol change with aging and exposure. The same is likely to be the case for other drugs and their interactions with alcohol.

4. Synergies with other NIH institutes raised by Mark Goldman (Q/A p2). An approach to synergies in strategic planning may be found in looking at the comorbidities of alcohol dependence/addiction. The highest comorbidity is nicotine addiction (34%) followed by antisocial personality disorder (29%), anxiety (19%) and mood disorders, especially major depression (17%) and drug use disorders (13%). Total rate of comorbidity is 60 percent. With these statistics, developed synergies with NIMH should be vigorously pursued.

The problem : FASDs are the leading cause of retardation in the world and costs and estimated $4 billon annually. Despite considerable efforts maternal drinking continues to occur at an alarming rate with full-blown Fetal Alcohol Syndrome representing approximately 0.6% of live births. More troubling is the estimated 10-20% of children exposed to lower, moderate levels of ethanol during fetal development. The effects of full-blown Fetal Alcohol Syndrome are clear based on dysmorphology evidence, however, the effects of lesser exposure are much more subtle but have a negative lifelong impact on health and behavior.

Impact on scientists: Unlike many developmental disorders, FASDs have a clear and known environmental cause related to drug abuse. For this reason alone inclusion of FASD research in NISUAD makes good sense because advances in our understanding of the consequences of fetal ethanol exposure can best proceed in the context of research on drug effects and addiction more generally. There are many other scientific benefits to inclusion of FASD research in the new institute. For example, among the major consequences of fetal ethanol exposure is an increased susceptibility to drug addiction in adolescence or later, which has been observed in animal models of FASDs as well. Further, advances in understanding of drug addiction and its consequences in adolescence or adulthood can benefit from information about the unique influence of drug exposure and abuse during these periods. An integrated approach that includes drug effects from the fetus throughout the life can provide such a framework, however, fragmenting these lines of across institutions with differing philosophies and emphases will necessarily reduce such integration. My fear is that moving FASD research, or any prenatal drug exposure work, to another institution would potentially harm not only this research but the potential scientific benefits such synergies provide. More generally, failure to include research on prenatal drug exposure, which is fundamentally an issue of maternal drug abuse, and to only focus narrowly on use and abuse on the individual in the new institute would, in my opinion, preclude opportunities to benefit from the commonalities inherent in these lines of investigation. In the long run I believe that this would do far more harm when weighed against the financial and scientific benefits associated with the more narrow focus outlined in the RFI. As a final point, it should also be recognized that many researchers who study prenatal drug exposure, including FASDs, also study drug use and effects at other time-points or in other models. The practical impact of fragmenting closely related lines of research across multiple institutes make inclusion of drug effects and abuse in one institute a much more attractive solution from purely scientific and practical perspectives.

Impact on the public : As a scientist, I believe that anything that is detrimental to the generation and/or communication of new knowledge is harmful. Thus, I do believe there is potential for negative impact on the public in relation to all of the substantive points I raised above. In this case, I believe failure to include prenatal drug and alcohol exposure within the scope of the new institute will harm these lines of work as well as those that have been highlighted in the RFI document. Ultimately this means that the public will be denied the benefits for treatments and prevention a broader scope would provide. When weighed against the potential benefits, both practical and philosophical, the gains simply do not sufficiently counter the losses. Finally, whatever the ultimate decision of the SMRB is it is very important to recognize the public health impact of prenatal drug effects and to ensure that research aimed at better understanding and treating the consequences of prenatal drug exposure are not negatively affected. The best prevention approaches are only modestly successful and even with improvement will never eliminate prenatal drug exposure, therefore, it is very important not to forget that the health and quality of life for individuals exposed to drugs prenatally will depend on discoveries made by scientists. I strongly urge NIH to protect funding for these important lines of investigation.

I strongly suggest that this area should include language that specifically emphasizes study of HIV/AIDS. Approximately one-third of HIV seroconversions among MSM can be attributed to non-injection substance use.

I urge the inclusion of research on substance use in relation to HIV/AIDS as s specific mission of the new institute.

Apart from prevention, existing data amply demonstrate that substance-abusing persons with HIV infection are much less likely than non-substance-abusers to enter, remain, and adhere to antiretroviral therapy for HIV disease. The reasons for these patterns are understudied. Research that identifies the nature of these associations and intervenes with substance-abusive HIV-infected populations is essential to new public health efforts to reduce HIV transmission through improved treatment and viral suppression.

I urge the inclusion of HIV/AIDS-related research as a mission of the new institute.

Critical point 2. Prevention must remain a priority. Establishment of a new combined institute should be used as an opportunity to strengthen NIH’s prevention portfolio. Prevention has demonstrated significant impacts in reducing onset and progression of substance abuse and it is essential that NIH not lose this focus (cites). Prevention is a national priority in the Obama administration and recognized as critical to the nation’s health. A recent report (2009) from The Institute for Medicine calls for Continued research on both the efficacy of new prevention models and real-world effectiveness of proven prevention and wellness promotion intervention as well as adaptation of research-based programs to cul¬tural, linguistic, and socioeconomic subgroups. I believe that the new institute’s mission statement must include an emphasis on prevention. I strongly endorse that the new institute elevate prevention to a research branch with funding allocated to alcohol and drug abuse prevention research at least equal to, and ideally greater than, the sum of the current levels at NIAAA and NIDA. This branch should also work to focus on translational research of prevention programs into real world settings. Prevention programming is a primary driver of the national economic benefits of substance use research investments.

Critical point 3. Drug and alcohol use are social behaviors. The proposed strategic plan over-emphasizes biological science compared to social and behavioral science. Substance use and abuse, particularly of alcohol, usually occur in social situations. Both currently and historically, use of specific drugs has been linked to identification with particular social groups, movements, or philosophies. Research suggests that initiation of these behaviors is largely environmentally determined, and that socio-cultural environments (e.g., policy, peers, family) play pivotal roles in the initiation and maintenance of and desistence from drug use, abuse, and dependence. Certainly there is an interplay of environmental and biological influences in the development of addiction, however, to downplay the social, cultural, and psychological aspects of substance use disorder is a fundamental miss that will severely weaken efforts at prevention and treatment and diminish the national economic contribution of work supported by the new institute.

Critical point 4. Integration with the NIH Roadmap. The new combined institute should have a clear plan for implementation of the NIH Roadmap for the Science of Behavior Change, for example, it could be a plan for how the behavioral sciences will be integrated into the biological and neuroscience portfolios.

Critical point 5. Interdisciplinary research is critical. Research on prevention and treatment of alcohol and drug abuse requires maintaining an interdisciplinary, multilevel perspective that takes into account comorbid disorders, such as mental health issues, and recognizes the role of social and environmental factors. It will be important as the two institutes combine that there is a strong commitment to interdisciplinary research.

Point of Clarification – What qualifies as “non-addiction research,”? Does “non-addiction research” include such things as HIV sexual risk behavior, health promotion and positive youth development interventions (that may have a number of benefits, including reduced or delayed drug use), and research on use or misuse that does not meet criteria for abuse or dependence (e.g., binge drinking)? Do these research areas fit into the new Institute or will they be referred elsewhere?

First, it is clear that individuals exposed prenatally to alcohol are at increased risk for developing addictions themselves. Therefore, FASD research should be seen as the beginning of a continuum of research to better develop methods of intervention to decrease addictions beginning at the youngest ages.

Second, fetal alcohol effects are the leading cause of developmental disorders and yet are inherently tied to the addictions of the mother. Therefore, it is clear that the best approach to limit this serious public health concern is to work directly with the mothers and women of child bearing age to reduce risky drinking. Therefore, it is critically important to link research developing effective interventions to reduce risky drinking with FASD research.

Third, individuals are most susceptible to developing addictions as adolescents and this important area of research may be fractionated by redirecting the child research NIAAA portfolio to be administered by the NICHD.

Finally, it is clear that in many, if not most cases, children born to individuals addicted to illicit substances are often exposed to multiple illicit substances. By separating the NIAAA child-related research from the addiction research, this will hamper the ability to fully understand the effects of multiple exposures on the development of the human nervous system and thereby hamper the ability to best address this growing concern.

My research is focused on identifying how alcohol disrupts intracellular mechanisms that control the way neurons extend processes and form appropriate connections – functions that are critical for normal brain development, but also for plasticity associated with learning and memory and for responses to injury. Neuronal shape, and changing shape in response to activity or other extracellular cue, is a key determinant of various neuronal functions that are disrupted by alcohol. Signaling pathways that regulate cell movements and shape are comparable across many different cell types, and are thought to be similar regardless of whether the cell is in a fetus or a mature individual. Indeed, our research has demonstrated that alcohol affects key signaling molecules (e.g. calcium, small Rho GTPases) linking extracellular cues to the cytoskeleton – thereby disrupting the cellular machinery controlling cell movements. These same signaling molecules are sensitive to alcohol in mature neurons, where they control structural changes associated with learning and memory, as well as responses to injury. Even more broadly, what we are studying is likely to provide insight regarding alcohol effects on other biological events that are critically dependent on cellular movements, such as immune responses, wound repair and metastasis. I derive considerable inspiration for our research from alcohol researchers working in these other model systems. To summarize, it seems arbitrary and misguided to treat our research as somehow less closely aligned scientifically with alcohol research – based simply on the fact that our model system is neurons developing and extending processes – when the same alcohol-sensitive cellular mechanisms are utilized by mature neurons, immune cells or cancer cells. I am firmly convinced that to delineate the molecular targets of alcohol, and to use these insights to design new, more effective treatments for alcohol addiction, we must continue to foster coordination of scientific discovery across multiple model systems. I hope you will agree that this will be best achieved by maintaining scientific and financial oversight of FASD research in a single institute.

2) Should the scope of the new institute be broader than addiction?

2) There has been some suggestion about removing certain areas of alcohol research (prenatal alcohol exposure and end organ damage as examples) to other institutes. This type of isolation would have devastating effects on these areas of research. It is critical that all aspects of alcohol research remain within this new institute. Fetal alcohol research, as an example, needs to be within an institute that focuses its research program on how alcohol affects not only brain but various organ systems, immune function, behavior, etc.

FASD is the single most important preventable cause of developmental disabilities. By far the most important strategy for preventing FASD is the prevention of drinking in women who are pregnant or trying to conceive. The defining face and brain abnormalities of fetal alcohol syndrome result from alcohol exposure during the third to fourth week of pregnancy, a time when most women do not know that they are pregnant. Hence, the prevention of FASD requires a concerted effort to reduce binge drinking in all women of childbearing age. Unfortunately, binge drinking is common, particularly in women in their late teens and early twenties. A broad array of clinical, psychosocial, and policy research has been directed at reducing drinking in this vulnerable population. That research needs to be coordinated to address the specific challenge of reducing binge drinking in women of childbearing age. Therefore, preventing the major public health burden of FASD will depend critically on the inclusion of all FASD research within the portfolio of an institute on addictions.

2. What would be the impact of the re-organization on ongoing research programs, including those on FASD?

2) To lose traction on focused alcohol research, health issues, and treatment would be a travesty. The exclusion of FASD would be another loss for the under-served and under-treated.

1. The research should remain in an agency that covers the development of the effects of the brain throughout the lifespan, not just the early development of the brain. 2. As research has shown that prenatal exposure to alcohol places children at increased risk for developing alcohol addiction, the research studies on FASD should be part of the portfolio of a comprehensive institute on addictions. 3. In order to present FASD, the single most preventable cause of developmental disabilities, a coordinated approach must focus on stopping women from drinking alcohol who are trying to get pregnant or who are pregnant. A broad range of clinical, psychosocial, and policy research has been conducted in the US and other countries focusing on reducing women’s drinking during pregnancy. This research with adults needs to be coordinated in a single Institute with a broad range of researchers working with adult addictions.

Our research at the University of Oklahoma Health Sciences Center has focused on preventing alcohol consumption by women in Russia; we have received excellent consultation and recommendations from the well-trained staff and consultants available through NIDA and NIAAA, adult focused research centers. It is my strong recommendation that the FASD research program continue to be housed in the Institute on addictions,

Thank you for your consideration of this recommendation.

Preamble: The idea that a new Institute may combine several research areas that are currently in other Institutes, in order to consolidate efforts and reduce redundancy is an intriguing idea. However, knowing which research areas go “together” in an Institute on Substance Use Addiction Disorders is a bit like the story of the blind men’s idea of what constitutes an elephant, it really depends on from which side you are "feeling" it. It is of the utmost importance that the motivation to combine certain areas of research is based on sound scientific data and not politically motivated reasons. Creating a new Institute by dismantling several existing Institutes and reshuffling will cause 5 years of “adjustment disorders” to staff and grantees and nobody wants to go through this with little supportive data that it will result in a better finished product.

I would like to give examples of 4 scientific areas that need careful consideration in this process. And, I would further suggest that each of these 4 areas be considered for cross-Institute RFAs, as test cases, which would be a much more expedient, less costly, and less disruptive process than combining Institutes. Once the benefits that could arise out of these RFAs could be assessed then consideration of whether and what should go into a new Institute could be put on a more firm scientific footing.

1) Creative and innovative research does not come from a machine that has a monolithic idea behind it. One of the most highly and hotly debated issues is whether there is a common mechanism for addiction to all substances (including nicotine). This is very much an open question and while some research (i.e. elegant imaging and electrophysiological experiments of limbic forebrain dopamine) give evidence that this could be true there is also ample evidence that it is not. For instance, genetic studies aimed at identifying genes underlying substance use disorders have shown that genes for alcohol dependence, in particular, do not overlap with those for other drugs of abuse/addiction (see Ehlers et al., 2004), whereas other areas of the genome appear to harbor genes for dependence on many drugs including nicotine (and cancer/COPD risk) (see Saccone et al., 2010). Providing a forum for the genetic consortiums in each Institute to meet, present findings, and combine data will advance this field. We do not need a new Institute to do this.

2) Do the mechanisms underlying “addiction” extend to other activities such as eating, gambling and sex? This is an extension of the first idea but looks at it from a different viewpoint. Recent genetic evidence suggests that some of the genes underlying drug dependence (including nicotine) overlap with the areas of the genome that harbor genes for body mass index (see Ehlers and Wilhelmsen, 2007). A potentially exciting construct underlying this finding is that there may be a set of “consumption” genes that influences both eating and drug taking. This set of genes may also influence metabolism (e.g. so called “fat sparing” genes), obesity, and cardiovascular risk, and/or they may share environmental risk factors (see Denoth et al., 2011). Would it not be more expedient to put together an RFA directly addressing this overlap rather than suggesting a new Institute be formed to include drug abuse, diabetes, cardiovascular disease and obesity?

3) Investigating the toxic effects of substances, especially alcohol, sugar, and fats, is not only important for understanding morbidity and mortality but impacts directly on the “Addiction” process. Two of the most exciting ideas in “Addiction research” that have appeared have come from studies on the effects of alcohol on the liver, gut and fetus. First discovered by researchers investigating the mechanisms of how alcohol produces liver disease it was discovered that it does so by activating two mechanisms. First of all, it changes the permeability of the gut (e.g. “leaky gut” syndrome) allowing gut bacteria and their by-products to enter the liver, and potentially harm the liver (Thurman et al., 1999). Interestingly, at the same time, studies showed that gut microbes may shape the host metabolic and immune network activity and ultimately influence the development of obesity and diabetes (see Musso et al., 2011). Taken together these studies suggest that a mechanism that we thought was only related to liver toxicity may influence consumption and addiction. The second mechanism is the ability of alcohol to initiate a cascade that leads to inflammation. It further turns out that alcohol also causes inflammation in the fetus, pancreas, and in the brain of the addicted individual using the drug (Lindros and Jarvelainen, 2005). In fact recent investigations suggest that the effects of brain inflammation may be an integral part of the development of “Addiction” itself (see Crews and Vetreno, 2011). Therefore, studying the process of inflammation in many tissues of the body (brain, gut, liver, fetus, pancreas, and adipose tissue) may uncover a very important general process of pathology including addiction. Again an RFA addressing this issue could be organized across institutes addressing this overlap rather than suggesting a new Institute be formed to include addiction, diabetes, liver disease, fetal effects and obesity.

4) The co-morbidity (co-occurrence) of substance use and abuse with other forms of mental illness goes way beyond the fact that certain disorders are often seen to occur together. In fact, recent evidence suggests that the risk that underlies drug use and certain specific mental disorders may come from shared genetic traits. For instance, several recent studies have demonstrated that post-traumatic stress syndrome (PTSD) as well as exposure to assaultive trauma are heritable (see Stein et al., 2002) and at least 1 study has shown that this shared trait overlaps with risk for alcohol dependence (Sartor et al., 2011). This means that it is not just the simple idea that a person is exposed to trauma, gets PTSD and decides to “self medicate” by drinking and using drugs but rather they have a shared genetic liability to all co-occur in that individual. There are in fact several other examples of this process including such disorders as manic-depressive disorder and substance use and antisocial personality disorder and substance use (see Dick et al., 2010), autism and alcohol dependence (see Schumann et al., 2011) and gambling and substance use. This is yet another suggested area of overlap that could be addressed by an RFA between Institutes instead of forming a new Institute that would include much of mental illness as well as substance use and addiction.

To conclude, the reasons that a new Institute should be formed should be based on a sound scientific basis that can be tested and evaluated. Trying out several cross Institute initiatives is a way to “test the waters” using the scientific method. This process should be transparent and not be swayed by political agendas only important “within the beltway” as this process has the potential to disrupt thousands of individuals in both the intramural and extramural communities for what appears at present to be intangible benefits.

References Crews FT, Vetreno RP. Addiction, adolescence, and innate immune gene induction. Front Psychiatry 2011; 2:19. Denoth F, Siciliano V, Iozzo P, Fortunato L, Molinaro S. The association between overweight and illegal drug consumption in adolescents: is there an underlying influence of the sociocultural environment? PLoS ONE 2011; 6(11):e27358. Dick DM, Meyers J, Aliev F, Nurnberger J, Jr., Kramer J, Kuperman S et al. Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. Am J Med Genet B Neuropsychiatr Genet 2010; 153B(6):1179-1188. Ehlers CL, Gilder DA, Wall TL, Phillips E, Feiler H, Wilhelmsen KC. Genomic screen for loci associated with alcohol dependence in Mission Indians. Am J Med Genet B Neuropsychiatr Genet 2004; 129B(1):110-115. Ehlers CL, Wilhelmsen KC. Genomic screen for substance dependence and body mass index in Southwest California Indians. Genes Brain Behav 2007; 6(2):184-191. Lindros KO, Jarvelainen HA. Chronic systemic endotoxin exposure: an animal model in experimental hepatic encephalopathy. Metab Brain Dis 2005; 20(4):393-398. Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med 2011; 62:361-380. Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S et al. Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD. PLoS Genet 2010; 6(8). Sartor CE, McCutcheon VV, Pommer NE, Nelson EC, Grant JD, Duncan AE et al. Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women. Psychol Med 2011; 41(7):1497-1505. Schumann G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D et al. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc Natl Acad Sci U S A 2011; 108(17):7119-7124. Stein MB, Jang KL, Taylor S, Vernon PA, Livesley WJ. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am J Psychiatry 2002; 159(10):1675-1681. Thurman RG, Bradford BU, Iimuro Y, Frankenberg MV, Knecht KT, Connor HD et al. Mechanisms of alcohol-induced hepatotoxicity: studies in rats. Front Biosci 1999; 4:e42-e46.

I also strongly urge that you ensure that substantial support for basic research on addictive processes, including work that embraces molecular, systems neuroscientific, pharmacological, physiological, and behavioral levels of analyses in animal models – has an important place at the new Institute.

Finally, I would like to echo sound input from the Research Society on Alcoholism that the new Institute should:

1) Reallocate its revenue-neutral budget to match the actual public health burden. Here, research on neuroadaptive-like changes associated with palatable foods high in sugar or fat should have a markedly increased budget relative to its current level. The remainder of the budget should be distributed approximately equally between 1) alcohol-related, 2) tobacco-related, and 3) illicit and misused prescription drug-related research. Such adjustments are essential if research efforts are to come close to matching the public health burden, even if they may be politically difficult for a new Institute administration whose fiscal base derives largely from current allocations as represented in the existing portfolio items.

2) Some consideration needs to be made as to whether medical complications that are viewed as derivatives of the substance abuse condition fall under the Institute’s jurisdiction (e.g.,for food, obesity, type II diabetes, gestational diabetes or overnutrition; for alcohol, fetal alcohol exposure or liver disease; etc.), Where another institute does not already currently exist explicitly to address the derivative medical condition (e.g., NIDDK for type 2 diabetes), then I feel that it is appropriate and most economical based on past experience that the new Institute be responsible for funding derivative conditions of the addiction.

3) The new Institute represents the perfect opportunity to address comorbidities of substance misuse, including the comorbidity between alcohol and tobacco use, for example. There has been debate, however, re: how other comorbidities should be addressed (e.g., post-traumatic stress disorder with substance abuse, for example). This is an important area that needs to be addressed given the nation’s recent experience with events anticipated to increase the incidence and prevalence of PTSD and comorbid drug/alcohol use disorders in the near future. I feel that Institute funding should be dedicated not only to polydrug comorbidities, but also to substance misuse disorders that are comorbid with other psychosocial conditions, even if those conditions individually (without comorbidity) might be addressed by other funding agencies (NIMH).

4) I think it is important that addictions to legal substances (e.g., alcohol, food, tobacco) or behaviors (e.g., gambling, computer use), not receive shortshrift at the expense of illicit substances (e.g., cocaine, methamphetamine) simply due to NIDA’s previous relationship with the Office of National Drug Control Policy because of their common interest in illicit drugs. The allocation of budget should, again, reflect the public health burden, and here, the public health burden of legal substances far surpasses that of illicit substances.

1) Encourage the development of new interventions for nonmedical staff to prevent and treat substance use, and to link substance users to appropriate treatment for HIV, hepatitis, sexually transmitted infections, and other infectious diseases. Over several decades NIDA and NIAAA researchers developed a series of substance abuse interventions, including relapse prevention, motivational interviewing, contingency management, and most recently Screening, Brief Intervention and Referral to Treatment (SBIRT). These interventions have been utilized primarily by non-medical staff who comprise the vast majority of the addiction workforce.

2) Promote the implementation and translation of behavioral addiction research to prevent substance abuse, HIV, hepatitis, sexually transmitted infections, and other infectious diseases. The science of implementation of addiction research has not extensively progressed and a number of evidence-based prevention, treatment programs have not yet reached the community. Advancing the science of behavioral implementing research to real work settings is crucial to address the growing epidemic of addiction and related consequences.

3) Encourage the development and implementation of addiction treatment and prevention approaches on co-morbidities (e.g., addiction, mental health, etc.) including depression, trauma and psychiatric disorders. Behavioral prevention and treatment on co-morbidities and their relationship to HIV and other infection diseases also require more attention.

4) Encourage research to support the study of transformation from an acute care model of addiction treatment for persons with severe substance use disorders (characterized by brief service durations and primary focus on achieving abstinence) to one of recovery management (RM). The latter is a framework for organizing services to promote sustained long-term recovery maintenance and includes promising practices relative to screening, assessment and level of care placement; service team composition and relationships; the locus of service delivery and shaping of post-treatment recovery environments, e.g. “recovery management check-ups” and holistic health. The RM model needs to be studied for its promise of more effective service outcomes, sound resource allocation, and controls in the rate of growth of healthcare costs. Such studies may also serve to identify contributors to late stage relapse, i.e. 5-10 and more years after achieving abstinence.

"Engage the medical community in prevention and treatment of drug addiction and alcoholism."

This opportunity restates a 15 year old strategy that has been long on intent and short on administrative science. The strategy within the opportunity needs to be considered and articulated in much greater detail. An efficient, outcome driven durable business model must be established to accesibly deliver your findings. Consider a case in point--Naltrexone (oral and injectible)is strongly indicated for treatment of alcohol dependence, especially when combined with psycho-social supports. Less than 3% of the population receives the medicine. Given the movement of the PPACA, we have an opportunity to redefine the business model for delivery of the evidence basis you will develop. Please strongly consider giving some realistic support to research and modeling cutting edge delivery systems. Thank you for your consideration and attention.

A). Pathways, Processes, Stages, and Styles of Long-term Recovery Research is needed to understand longitudinally the multiple pathways to long-term recovery. As a person goes along his or her recovery path, they experience a life filled or refilled with work, a place to live, relationships, and activities in the community. Research should examine how a person integrates recovery into an expanding quality of life and the stages that this process happens at with a community/environmental perspective. Factors to be examined should include health, quality of life, variety of self-help programs, and community service in long-term recovery.

We also need to understand what the factors are that contribute to initiating alcohol and drug use after a period of sustained recovery. How often do people start using again across the life cycle of recovery? Are there points of vulnerability associated with age, primary drug(s), recovery pathway, gender, race/ethnicity, sexual orientation, or presence of co-occurring medical/mental health disorders? Are there critical transition points from early recovery to sustained recovery and from recovery maintenance to enhanced quality of life in recovery that increased risk of relapse? Does the availability and use of peer and other recovery supports, recovery institutions such as recovery community centers, recovery schools, recovery-oriented employers, recovery residences, alcohol- and drug-free recreational activities, affect a person’s ability to sustain recovery for the long haul?

The impact of research in this area would be of great interest to the public and policymakers – it would demonstrate the reality and pathways to recovery to a public that is skeptical about the ability of loved ones, friends and co-workers to recover from addiction to alcohol and other drugs. Research that found that recovery from addiction was a contributing factor to lowering recidivism rates for people re-entering communities from incarceration could assist policymakers in making decisions about policy and funding priorities.

It should also be of great interest to scientists seeking to understand the management of this behavior – mainstreaming addiction recovery research with research on other manageable chronic health conditions and providing information about the solutions to a problem that has been well researched and documented.

B). Recovery patterns and experiences for specific groups of people including young people, women, and parents in recovery. This research area should be of great interest to policymakers as well as to the public and scientists. The earlier that a person identifies and embarks on his or her pathway to long-term recovery, the better in terms of personal health and wellbeing, family and community health. The costs of addiction are dramatically reduced as well; benefiting taxpayers and communities.

Using young people as an example, some of the questions that could be asked include: • What is the prevalence of recovery among young people; is it increasing, decreasing? • Are there predictable stages of recovery for young people? • Do the recovery rates of young people differ by gender, ethnicity, drug choice or other variables? • Does a family history of recovery affect a young person and/or other family members’ recovery? • Do young people whose families are affected by ongoing alcohol and other drug problems have better opportunities for sustained recovery if they sever family ties? • How can parents, other family members and significant people in a young person’s life best help him or her to initiate and sustain recovery over a lifetime? • What are the effects of post-treatment monitoring, recovery coaching and assertive linkage to communities of recovery on long-term recovery outcomes for young people? Are they different than for adults? For parents in recovery, some questions that could be asked include: • If a son or daughter is at increased risk of developing an alcohol or drug problem because they and one or both parents share a family history of such problems, do the children have less risk of developing problems if the parent is in long-term recovery? • If one or more children were to develop an alcohol or drug problem, are their prospects of recovery better because of the parents’ recovery? • What strategies of prevention and early intervention can specifically lower the risks of children of recovering parents developing alcohol and other drug problems at an early stage? What effect does the participation of a family member in specialty sector addiction treatment and/or recovery mutual aid groups have on the recovery prospects of other family members? • What changes should a person anticipate in early recovery in relationships with children and other family members? • What does it mean when parents who have lost custody or left their children during their active addiction seek to re-establish contact with their children? Will this harm or benefit the child and if so, when and how? • What evidence-based models are available for peer-based support for parents in recovery, e.g., parenting guides/sponsors?

C). Communities of Recovery. How does the level and degree of exposure to communities of recovery and recovery-oriented communities affect a person’s individual and family member recovery? Do community supports such as faith-based organizations, opportunities for community activities/advocacy strengthen recovery and affect community wellbeing? What is the impact of having multiple housing options available for people in early or long-term recovery available mean to building recovery-oriented communities? Are there specific activities, events or developmental issues that pose significant challenges to recovery and community health? If so, what works to support recovery and community health?

D). Recovery self-management. Growing numbers of people seeking addiction recovery are developing recovery plans that they modify over time to reflect their progress in reaching recovery goals. Does it make a difference if a person develops his or her own recovery plan in a community or clinical setting compared with the development of a treatment plan by a clinician?

E). Peer and other recovery supports. Non-clinical recovery support services are offering people seeking or in recovery new services based in the community. These services can be used alone, in combination with mutual aid and/or professional treatment. What are their effects on the person seeking recovery as well as the person providing the service?

F). Recovery support institutions and service roles. Over the last ten years a growing number of recovery community organizations have pioneered the development and delivery of peer recovery support services for people in or seeking recovery from addiction to alcohol or other drugs. These organizations provide services in a variety of diverse settings, including recovery community centers and recovery residences, as well as host of other settings outside of the recovery community including jails and prisons and medical settings. Peer recovery support services and organizations that provide them have been operating virtually unnoticed until the emergence of the health reform-related focus on prevention and wellness, an emphasis that highlights recovery-oriented systems of care and implementation planning.

These nonclinical services often assist individuals and families and include peer recovery coaching, recovery community centers, recovery residences, job readiness programs, financial management training, educational/ employment assistance, and telephone check-ups. These services are provided prior to, during, after or in lieu of treatment and other clinical services and support. The use of peer support is, by now, a common practice in many fields. While professionals treating chronic illnesses are often knowledgeable about peer services, there is still limited awareness among individuals and families. In today’s medical world, peer support is recognized as a valuable adjunct to professional medical and social interventions. Improved outcomes are particularly notable when peer support services are provided to people with chronic conditions that require long-term self-management. The peer recovery support services offered by recovery community organizations and others are supported by a long, well-documented, and replicated evidence-based tradition. Peer recovery support services hold promise as a vital link between systems that treat people with addiction in a clinical setting and the larger communities in which people seeking to achieve and sustain recovery live. Awareness of the existence of these various groups and supporting research is critical.

There is a robust body of research on the value and effectiveness of peer supports for a number of chronic health conditions such as diabetes, cancer, obesity, HIV/AIDS and mental illness. This research has identified the value of services delivered by peers at the community level and the usefulness of a wide variety of social and other supports.

There has been limited research on the effectiveness of addiction peer recovery support services, mostly focused on recovery residences (housing). While there is a good start on this research, there is very little research on other recovery support institutions such as recovery schools, recovery community organizations, recovery community centers, recovery industries or recovery ministries. And there is next to no research on the emerging peer and other recovery support service roles of recovery coach and peer recovery support specialist.

G). The Neurobiology of Recovery NIDA’s studies of the brain should also focus on brain resilience and recovery. To what extent and how does the brain heal? How does long-term recovery affect this process?

NIAAA’s studies of the health impact of alcohol dependence should also focus on the health impact of recovery from addiction. To what extent and how does health improve? How does long-term recovery affect this process?

Thank you for allowing for input into this important strategic plan.

HIV/AIDS and drug abuse are inextricably linked and coalesce in virus transmission not only through injection drug use, but importantly through risky behaviors induced by the effects of drugs and alcohol which impair judgment and decision making. Individuals with substance use disorders are at risk of viral infections and if infected they may be contagious and transmit diseases to others. The public health and scientific benefits of including behavioral and services research related to HIV/AIDS and substance abuse as part of the Scientific Strategic Plan for NISUAD cannot be overstated. It is critical that contracting and transmitting HIV/AIDS be researched through the substance abuse/use perspective. HIV/AIDS and substance disorders are syndemic diseases, i.e., they interact and are not independent. Adherence to ART/HAART is a public health concern that must be considered within the aggregate of HIV/AIDS and addictive diseases and their synergistic interactions. Medication development and adherence issues in drug abusing populations are different than in other populations as witnessed by the historical exclusion of drug abusers from clinical trials for new HIV/AIDS medications. The best place and most scientifically appropriate home for behavioral and services research regarding HIV/AIDS among drug and alcohol abusers is within NISUAD, an Institute where the long term strategic plan includes a primary focus on substance use and addiction disorders.

Co-Occurring mental health disorders and drug abuse are also inextricable linked. In the U.S., our bifurcated system of services and funding for mental disorders and substance use disorders is replicated at the NIH in terms of separating the diseases into different institutes. While there is a need for this separation, there must be recognition that there is an intersection where individuals and public health needs must be addressed. About 50% of the individuals entering the substance abuse treatment system are also afflicted with a mental disorder, whereas approximately 50% of the individuals entering the mental health treatment system also have an addictive disorder. Each system is equipped to handle certain portions of the population with these co-occurring disorders. Typically, the mental health system treats clients “with severe and chronic mental illnesses” but is “not equipped to address the treatment of concurrent substance abuse disorders,” whereas “the substance abuse treatment system addresses all types of substance abuse disorders at all levels of severity; when necessary, many providers in this system are able to respond to mild to moderate forms of mood, anxiety, and personality disorders.” (U.S. Department of Health and Human Services, 2002, p. v). Thus, NISUAD and NIMH should continue their research ventures within the needs of individuals afflicted with co-occurring disorders, and the mission of NISUAD should be broad enough to encompass the public health needs of individuals with substance use and mild to moderate forms of mental disorders.

Recommendation. It is critical that the mission of, strategic plan for, and research portfolio of NISUAD include HIV/AIDS and Co-Occurring mental disorders.

Thank you for this opportunity to respond to this Request for Information and offer my thoughts on what should be included in the mission, strategic plan, and portfolio of the new Institute.

It would be a shame to loss what we have gained in regards to research on FASD. My family is counting on YOU to do the right thing and continue NIAAA funding for FASD research.We have recently brought togetehr a group of individuals with FASD who are aging and there is no research at this time to see what is happening to them. By moving teh research away from the mom, we will lose a great deal of information.

1. Susceptibility to addiction is greatest from early adolescence through the mid 20s, a time when the brain is still developing. The study of addiction depends crucially on understanding how alcohol affects the developing nervous system. Brain development begins during embryogenesis and does not cease until the third decade of life. Much of NIAAA's FASD portfolio focuses on the effects of alcohol on the developing nervous system. Alcohol interacts with many of the same molecular targets during prenatal and early postnatal brain development as it does in the developing adolescent and mature nervous systems. There is no scientific rationale for dividing the NIAAA brain research portfolio at any arbitrary point in the 3-decade timespan of human development. Therefore, all research on alcohol's effects on the developing nervous system should be coordinated and funded by a single institute.

2. Prenatal alcohol exposure permanently alters the structure and function of neurotransmitter pathways that mediate alcohol addiction. Children exposed to alcohol in utero are at increased risk for developing alcohol addiction. The comprehensive study of alcohol abuse and alcoholism requires the coordinated investigation of all factors that predispose to these disorders, including prenatal alcohol exposure. Therefore, preclinical and clinical studies of FASD should be an important part of the portfolio of an institute on addictions.

3. FASD is the single most important preventable cause of developmental disabilities. By far the most important strategy for preventing FASD is the prevention of drinking in women who are pregnant or trying to conceive. The defining face and brain abnormalities of fetal alcohol syndrome result from alcohol exposure during the third to fourth week of pregnancy, a time when most women do not know that they are pregnant. Hence, the prevention of FASD requires a concerted effort to reduce binge drinking in all women of childbearing age. Unfortunately, binge drinking is common, particularly in women in their late teens and early twenties. A broad array of clinical, psychosocial, and policy research has been directed at reducing drinking in this vulnerable population. That research needs to be coordinated to address the specific challenge of reducing binge drinking in women of childbearing age. Therefore, preventing the major public health burden of FASD will depend critically on the inclusion of all FASD research within the portfolio of an institute on addictions.

Much work is currently being conducted by the NIAAA on Fetal Alcohol Spectrum Disorder (FASD), but more needs to be done. 20% of women continue to drink during pregnancy and approximately 40,000 babies are born each year with the disorder, making it the number one cause of preventable birth defects.

It is imperative that we better understand the link between maternal alcohol use and FASD. Currently, it is unclear whether FASD will fit within the definition of “addiction research” the new agency is tasked with conducting. The potential separation of research on alcohol use during pregnancy and FASD would be detrimental to the effort to fully understand the link between the two, and to conduct streamlined, synchronized research on preventing and treating FASD. When determining the shape of the Scientific Strategic Plan it is crucial that FASD research does not get “lost in the shuffle.” The configuration of the new institute, whose portfolio will arise from the strategic plan formulated with input from the scientific community, must make FASD research a high priority.

Improving prevention efforts by developing a better understanding of the patterns and trajectories of drugs of abuse and their influence on brain development

In determining the Scientific Strategic Plan, it is essential that NIH realize the important role it can play in curbing maternal alcohol abuse. There are several areas of research related to FASD and alcohol abuse during pregnancy that should garner much more attention, prevention being at the fore. Development of an accurate biological screen for binge drinking or exposure to alcohol during early pregnancy offers one opportunity where the return on investment could greatly improve our Nation’s health and curb the lifetime of complications that stem from FASD and alcohol use during pregnancy.

Engaging the medical community in prevention and treatment of drug addiction and alcoholism and encouraging patient recognition and utilization of effective substance abuse treatments

As a leader in public health efforts, the NIH should research and initiate an information-based campaign to address alcohol abuse during pregnancy. Facts on the complications caused by drinking during pregnancy need to be more effectively disseminated to many more women of reproductive age as well as a broad range of physicians who treat them. Public awareness through advertisements and Public Service Announcements, similar to the current campaign to curb tobacco use, offers a potential avenue to reach the many women who may not be receiving proper prenatal care. The Scientific Strategic Plan should incorporate the many public health opportunities to curb alcohol abuse during pregnancy.

The effects on the public of prenatal alcohol exposure are enormous. From increasing the chance of the offspring exhibiting increased propensity for alcohol use later in life to problems of ADHD and learning in general. The public interest in this research should be immense.

I am a Professor in the Department of Surgery at Michigan State University. In the United States, alcohol abuse is one of the leading causes for traumatic injury and liver disease. Organ tissue injury caused by alcohol use and abuse is a major focus of our investigation. Our studies are to elucidate the adverse effect of alcohol on host immune defense, tissue injury repair, and tissue regeneration. Most of these important investigations are currently funded by NIAAA. I would strongly recommend on behalf of our program at Michigan State University and colleagues working in this field elsewhere that alcohol, trauma, host immune defense and end-organ injury should remain a major focus of the new institute as any disruption of funding in this area of research may severely hamper the progress in improving patient care for excessive alcohol consumption associated trauma and organ injury. As the Director of Surgical Research at Michigan State University, I have a serious concern about the merger of NIDA and NIAAA into an Institute focusing primarily on addiction and addictive behavior. As we all know that alcoholic beverage is the most frequently consumed beverage in the public social events. Binge drinking and the associated acute intoxication are responsible for most incidences of trauma and organ tissue injury. Approximately 50% of the adult trauma patients who are admitted to the hospital consumed alcohol prior to sustaining their injuries. Acute alcohol intoxication profoundly suppresses host immune defense, which increases the incidence of secondary bacterial infection. These particular health problems caused by binge drinking and acute alcohol intoxication are not necessarily associated with any addictive behavior. I strongly suggest that alcohol consumption and end-organ injury should remain a major focus of the new Institute.

Second, there is a complex interplay between alcohol abuse / alcohol addiction and the long term effects of fetal alcohol exposure. Clearly, alcohol abuse and alcoholism during pregnancy are the greatest risk factors for FASD. Conversely, among the many adverse consequences of fetal alcohol exposure is an increased risk for developing patterns of behavior that lead to alcohol abuse and alcohol addiction. Better comprehension of how fetal alcohol exposure predisposes adolescents and young adults to alcohol abuse and addiction requires continued coordinated research and scientific communication between the FASD and the alcohol addiction research communities. Separating the FASD research portfolio from the remainder of the alcohol addictions research community will surely diminish progress towards a better understanding of these relationships and will diminish or delay the prospects of improved care and treatment for these complex disorders.

Thus, the portfolio of basic science, clinical and community-based research on FASD should be sustained as an important part of a single institution supporting research on the molecular mechanisms and long-term consequences of alcohol abuse and alcohol addiction.

merging NIDA and NIAAA is a great idea. I would also like to see them merged with NIMH, since i think there is actually no clear line between the three of them.

2) As troops return from over 10 years of war, with many suffering from PTSD, depression, TBI, and other problems that can promote alcohol misuse, there is a military problem that is becoming a public problem. Alcohol is a socially acceptable, legal form, yet debilitating and socially and physically destructive form of substance abuse for these soldiers who have served our country so well. If not NIAAA, who will find better ways to help those soldiers?

3) Unlike other drugs of abuse, alcohol has profound effects on the whole body, and the body’s processing of alcohol has an effect on the process of intoxication and damage, as do the diseases (liver, for example) that are caused by alcohol misuse. What the public is going to miss out on, never even see, is the benefit of NIAAA’s recognition that alcohol misuse has to be treated as a system-wide problem. The very design for the merged institute removes the issues of alcohol that are not currently seen as directly related to its addictive properties.

4) Something unusual about alcohol, in comparison to other substances, is that at moderate doses, it can have benefits for some people, while for others it poses risks of cancer or heart disease. It is a profound benefit to the public to understand those risks and benefits, and if the system-wide perspective of alcohol’s effects is eliminated from the institute, the probability of understanding the benefits of alcohol will be low. It will simply be very unlikely to have the right combination of people looking at the systems issue.

In summary, the primary effect on the public will be to lose education and understanding that are coming from a systems approach to alcohol. This kind of loss will probably go unnoticed by the public, because it is largely preventative and for benefits that do not exist yet.

Effects on Scientists: 1) The effects on scientists will be a reduced attention to alcohol research. One might say that the new institute will pay attention to alcohol, but the current size of the relative budgets of NIDA and NIAAA show that far greater interest is invested in drugs other than alcohol, even though the damage caused by alcohol is tremendous. Creating a new institute will not change the disparity of funding for alcohol research, and it will very likely make it worse, because alcohol research will no longer be a visible, separate entity.

2) As funding for alcohol research becomes more difficult, young scientists who are in their most creative years will be drawn or forced in directions away from alcohol research. One might, as a solution, propose training specific to alcohol research, but if funding after the training period is too sparse, they will do something else, instead. The population of new minds with new perspectives for treatment will slowly be reduced.

3) An additional loss will be from established scientists forced to abandon the field because of loss of funding. Yes, the ideal is that the new institute will fund alcohol research at least as much as it has been, but the fact of the loss of systems effects from the institute’s program means immediately that some work will end. As mature scientists leave the field, new ones grow less likely to find or encounter mentors to guide them in alcohol research, so the reduced number of young scientists will be less likely to find people to draw them to this area of work.

In summary, the effects on scientists will be to discourage the entry of new, creative people into the field of alcohol abuse. It will gradually eliminate more advanced researchers, compounding the problems of young researchers because of a lack of mentors. Alcohol research will almost certainly, in the long run be reduced by a loss of financial support and minds.

2) Continued funding, at least proportionate to what is currently spent on other drugs of abuse that have greater visibility but less societal and health impact than alcohol does. This position is important to maintain, or alcohol research will certainly suffer. Solving this issue will also maintain the ability to continue the flow of new, creative researchers into alcohol research to introduce new ideas and replace scientists who retire. Could a mandate be introduced that forces this to happen?

3) Systems-wide perspective on alcohol abuse. The interactions of the brain and other organs, from prenatal ages to senescence, should be maintained, because the public health impact derives from the effects on the entire body, and not just the brain.

4) The positives of the proposed reconstitution are, ideally, integration of perspectives of alcohol and other substances of abuse. Those can and should be encouraged under any circumstances, even without a unification of the institutes.

Alcohol use disorders represent one of the leading sources of preventable deaths and are a huge economic and social burden, in part because alcohol is legal and prevalent. Tobacco smoking also exacts enormous costs for similar reasons, and in fact tobacco and alcohol research should be placed within the same institute because of the strong alcohol/tobacco comorbidity. One concern is that alcohol and tobacco research not be overlooked or downplayed simply because they are legal substances. Research into addiction for illegal drugs is very important, but funding support for different addictive substances should in part reflect their impact on the society we are trying to aid. Thus, it will be crucial to maintain sufficient funding for alcohol and tobacco to allow the novel discoveries that will facilitate development of new and effective treatments.

It is also critical that the new institute maintain research into social, policy, preventative, and therapeutic areas. Such work provides important direction for neuroscience and physiology research by defining the characteristics of the actual patient populations we wish to help. For example, social research can help define the pathological patterns of behavior in addicts, neuroscience can help elucidate the neural mechanisms that drive the problematic pathological behaviors, and novel therapies and interventions will be generated at the interface. The NIH seeks to promote research with synergy between different research areas, and this goal will be best served by maintaining a diverse research program including society and policy as well as systems biology.

The economic harms of excessive alcohol intake/smoking are related in part to damage to organs other than the CNS, and the pattern of intake is likely to have important consequences for downstream physiological damage. Thus, research on organs other than the brain should be retained within the same institute that studies the behavioral and neuroscience mechanisms that give rise to such patterns of intake.

Although there are similarities among addictions for different substances of abuse including alcohol, there are also many important differences. These range from the patient populations impacted to the different compensatory molecular and physiological changes. This is especially true for alcohol, which acts through many more target molecules relative to other addictive substances. Thus, medications under development to treat addiction may or may not be useful across different addictive substances. In fact, an appreciation of the similarities and differences between addiction to different substances will only enhance our overall ability to be therapeutically effective.

Thank you for your consideration.

A key issue for the new institute is whether it will consider the problems of substance use and addictive disorders from a narrow or wide perspective. Focusing too narrowly on neuroscience of substances will set back efforts to address the wide panoply of problems that impact health and society. An important NIAAA strength, the integration of research at all levels, from molecular and cellular effects of ethanol through systems biology to both addiction and disease, and then to the impact on society and strategies for reducing negative impacts, should be a model for the new agency. In particular, the integration of alcohol-related diseases (including liver diseases, FASD and cancer) and the effects of alcohol on other diseases (including beneficial effects on cardiovascular disease) with the study of alcohol consumption sets a strong precedent for the new institute. If alcohol-related organ damage/disease is divorced from the institute that focuses on alcohol in all of its facets there is a significant risk that important issues will be neglected. Likewise, moving treatment, prevention and policy issues to a different agency may leave them orphaned.

In terms of the addictive properties of alcohol and drugs, it is clear that nicotine belongs with these other drugs. There are, in fact, more similarities between nicotine and alcohol than between alcohol and illicit drugs of abuse, including the high prevalence of exposure (drinking, smoking), high comorbidity, and the delicate policy issues that arise in confronting problems with legal substances. Funding of studies on alcohol and nicotine should be greatly increased, commensurate with their huge societal impact.

Comorbidities need more attention, both in the laboratory and in population and clinical studies. Too often, people with comorbid conditions (other drugs, other psychiatric or somatic illnesses) are excluded from studies on one drug or disease to simplify analysis, but that hinders studies of the patients that we are trying to help. Taking these complexities into account will increase the costs of individual studies, but increase their value even more.

B. However, I am extremely concerned that the addiction mission may not be effectively consolidated in the new institute. This concern has several components including:

1. If important components of the tobacco/nicotine addiction portfolio remain outside the proposed institute, the effort to consolidate addiction research (in this case, the most commonly abused drug) would be compromised.

2. It is extremely important to retain the study of the neurodevelopmental effects of abused substances (alcohol - fetal alcohol syndrome; nicotine - risk for ADHD; etc.) within the addiction institute. First, these neurodevelopmental effects are best understood within the context of the overall study of the effects of these substances on the brain. Second, the effort to prevent the neurodevelopmental consequences of addiction are going to reflect the combined effort to treat addiction in the mothers and mitigate the ill effects of these substances in the fetus. Third, addictions are neurodevelopmental disorders. It would introduce barriers to science to split off the antenatal period from the remainder of the research on the neurodevelopmental effects (particularly during childhood and adolescence) of abused substances.

3. I believe that it is similarly ill-advised to split off the medical consequences of addiction from the rest of addiction research. First, at the level of biology, the signaling mechanisms underlying the toxic effects of these drugs shares many features with the addiction-related effects of these drugs. There are scientific synergies associated with linking these areas of research. Second, the effort the prevent the medical consequences of addiction reflects the combined and united effort to prevent them (i.e., to prevent and treat addiction) and to treat the toxic effects of these substances in relevant tissues in the body. In some cases, the brain for example, the toxic effects likely contribute to the addiction process. The addiction institutes developed their medical portfolios (liver, heart, lung, HIV, etc.) because these areas were neglected by the "organ-based" institutes. These addiction institutes have become experts in this area over the past decades. It would seem that splitting off these areas of medical research would hamper rather than facilitate progress.

C. I am extremely concerned that the financial cost and the scientific and administrative disruption associated with creating the consolidated institute may outweigh the benefits of the consolidated institute. To this end, we have been assured that the budget of the new institute would not reflect a cut to the addiction research mission. However, I have not seen indications that there would be an infusion of funds to the new institute to cover the administrative costs of the consolidation. Thus, particularly at a time when funding seems so tight, there would seem to be reductions in addiction research funding related to the merger. In addition, there do not appear to be new resources set aside for the new emphasis on research on the abuse of multiple substances.

In summary, I am excited by the opportunities that would emerge from closer collaboration of NIDA, NIAAA, and other institutes in the service of reducing the impact of addiction. The creation of a consolidated addiction institute is certainly one path to achieve that end. However, it is extremely important that any steps toward consolidation protect the addiction research mission. As noted above, there are many aspects, both financial and scientific, that raise concern. I would support a consolidation plan that preserved the integrity of the addiction research mission along the lines that I outlined above. However, I would oppose a structural consolidation plan that was advanced at the cost of the nation's addiction mission, which is served ably currently by NIDA and NIAAA.

1. FASD is different from other neurodevelopmental disorders in that it is entirely preventable. Moreover, FASD does not occur in a vacuum. It is the direct result of maternal alcohol use, abuse and addiction, and cannot be understood in isolation, apart from the mother. The maternal-fetal system are interconnected, and the mechanisms underlying the numerous adverse effects of alcohol on physical, neurobiological, cognitive and behavioral outcomes of offspring can only be investigated and understood in the context of the maternal-fetal unit. Factors such as maternal and fetal genetics and gene x environment interactions, diet, drinking pattern and amount consumed, stress, health status, and physiological function are risk/resilience factors and will all influence fetal outcome. One needs both the alcohol exposure information and information about the mother in order to understand fetal outcome. Trying to understand effects and investigate mechanisms of prenatal alcohol exposure on the offspring in isolation from the mother is impossible, if key information on maternal history, factors involved in mediation of alcohol’s effects, and biomarker information are lost.

2. A Consensus Statement from a recent Consensus Conference on “Recognizing Alcohol-related neurodevelopmental disorder (ARND) in primary health care of children”, sponsored by the Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders, NIAAA, the CDC and the American Academy of Pediatrics, highlights this point. It was recommended that “For children, pediatric primary health care clinicians should obtain medical records about prenatal alcohol exposure and other potential risks from the birth mother’s obstetric caregiver. For children who are not living with their birth parents, clinicians should obtain any available records that may provide information about prenatal alcohol exposure or other relevant family history.” This statement represents a dramatic advance in thinking for pediatric primary health care clinicians, who have focused historically only on the child. If studies on the child and the mother are separated into different institutes, such an approach will be seriously undermined.

3. Research related to mechanisms underlying alcohol’s adverse effects and to the development of interventions for and treatments of both the mother and child will also be compromised by separating the mother and child into different institutes. This is true from both the basic science and public health perspective.

A prime example from the basic science perspective comes from the field of epigenetics, a key initiative in many institutes within NIH, including NIAAA. Increasing evidence suggests that investigation of possible epigenetic mechanisms as mediators of alcohol’s adverse effects on the fetus provides a promising approach for understanding the complex phenotypes associated with FASD, and the persistence of these characteristics into adulthood. Some of the strongest evidence for epigenetic processes comes from data suggesting that both preconception and preimplantation alcohol exposure, when the embryo is not yet implanted in the uterus and thus not yet connected to the maternal system, can cause adverse effects. Paternal alcohol consumption may be one route through which preconception effects of alcohol can occur, through DNA methylation of the sperm. In addition, numerous preconception and preimplantation effects of maternal alcohol consumption have been described. Epigenetic processes are likely involved in prenatal alcohol effects throughout gestation as well. A possible role for epigenetic mechanisms in intervention for FASD, including a focus on maternal dietary factors such as folate and choline, provides a novel approach to intervention. This research is all driven by a focus on the maternal-fetal-child and/or paternal-fetal-child units, and would likely be seriously compromised if research on the mother and research on the fetus/child are done in isolation from each other.

A prime example from the public health perspective concerns efforts to reduce drinking in women of child-bearing age. Under the aegis of NIAAA, a broad array of clinical, psychosocial and policy research has been directed at reducing drinking in this vulnerable population. Separating research on the mother and child into different institutes will seriously weaken the development of public health initiative aimed at reducing or eliminating drinking during pregnancy. From a public health perspective, for both prevention and intervention, one must target the health of Thus, preventing the major public health burden of FASD and developing a coherent public health strategy for FASD will depend critically on the inclusion of all FASD research within the portfolio of an institute on substance use, abuse and addiction. 4. The majority of American adults who drink alcohol are not alcoholic, but rather recreational or moderate drinkers. These individuals will likely not fall under the purview of the new addictions institute. Yet moderate levels of alcohol exposure, while not causing FAS, are known to have serious long-term adverse effects on fetal and child development, including numerous behavioral, cognitive, and physiological effects. Inclusion of FASD within the portfolio of the new institute will allow for targeting of these individuals in public health campaigns focused on prevention of FASD, and will allow for research related to all aspects of the adverse effects of prenatal exposure to alcohol.

5. Infants and children with FASD grow to adolescence and adulthood. Their developmental disabilities do not go away, and new problems often arise as they mature. Many of these individuals develop so-called “secondary disabilities” including depression and anxiety disorders, substance use/abuse/addiction problems, problems with the law, social problems, and other issues. Many of these individuals are never able to live independently. Moving the FASD portfolio into NICHD will exclude research on adults with FASD from consideration.

For all of these reasons, from both a scientific and public health perspective, it is the right decision to retain the FASD portfolio within the new substance use, abuse and addiction institute.

Basic and translational behavioral science has contributed in substantial and enduring ways to our understanding of addiction. The formation of the National Institute of Substance Use and Addiction Disorders (NISUAD) presents an exceptional opportunity to expand upon the crucial role of behavioral science. NISUAD will be uniquely positioned to support basic behavioral research, and to influence its direction. The discovery that drugs act as potent reinforcers by Charles Schuster (a former NIDA director), Roy Pickens, and Travis Thompson transformed addiction science and led to a range of evidence-based treatments that are still being disseminated across a multiplicity of settings. Basic research also gave birth to pre-clinical models to isolate and assess novel behavioral and pharmacotherapies for addiction. Cutting-edge basic behavioral research continues on a range of topics in addiction. This work includes the influence of delay discounting on choice for drugs and other risky behavior, the role of associative processes in substance abuse and relapse, the importance of conditioned reinforcers in drug use, and the behavioral economics of substance abuse. Thus, behavioral research continues to transform our understanding, and it promises to lead to new strategies to prevent and treat addiction. WE URGE THE NEW NISUAD TO PRESERVE A SIGNIFICANT ROLE FOR BASIC AND TRANSLATIONAL RESEARCH OF BEHAVIORAL PHENOMENA. In addition to the behavioral research described above, advances in neuroscience and genetics are increasingly being linked with basic behavioral phenomena. It is truly exciting when behavioral science and allied disciplines come together to form a deeper understanding of addiction. But these advances cannot occur without continued support for basic behavioral research. In any research portfolio, at some point the question will be asked about the behavioral significance of the phenomena under study. Answering this question will require basic behavioral research in animals and humans. Critical issues that basic behavioral research can address include: • THE ROLE OF CHOICE AND BEHAVIORAL REGULATION IN SUBSTANCE ABUSE. This includes the choice between drug use and other activities, self-control, delay discounting, modulation of incentive motivation, and response-inhibition in both animal models and in people.

• THE TRANSITION FROM TREATMENT TO COMMUNITY. The point at which an individual returns to the environment in which abuse occurred is a period of great vulnerability. We need to understand the basic processes of how such environments foster use and how to build resistance to these influences.

• THE ROLE OF ASSOCIATIVE PROCESSES, INCLUDING CONDITIONED REINFORCEMENT AND OCCASION-SETTING. These environmental factors contribute to the development of abuse, foster and enhance the impact of addictive substances and activities, and are critical determinants of relapse.

• THE DEVELOPMENT OF QUANTITATIVE MODELS OF DYSREGULATED BEHAVIOR. Such models provide formal content to otherwise ambiguous psychological constructs and thereby guide the identification of neural structures and functional relations that underlie addiction.

• THE ROLE OF ENVIRONMENTAL FACTORS IN RELAPSE. It would be difficult to overstate the importance of conditioning principles in relapse. We know that events paired with drug reinforcers occasion drug use and cravings but we have a poorer appreciation of how to exploit this understanding to program, for example, the generalization from treatment to community and domestic environments or to apply associative processes in predicting or preventing relapse.

• TRANSLATIONAL STUDIES TO IMPROVE TREATMENT. Direct application of behavioral economic principles can be found, for example, in the emergence of contingency management and other behaviorally based approaches to manage, treat, and prevent addictive disorders.

• CONTINUED SUPPORT FOR RESEARCH ON ADDICTIVE DISORDERS IN GENERAL. This includes gambling and other addictive disorders that do not involve drugs. It is our understanding that this support will continue, but we feel that this is so important that we wished to strongly endorse it.

By clearly articulating a role for basic behavioral research, NISUAD can become a leader in basic and translational behavioral science. Our understanding of conditioning processes advanced significantly because of the support of NIDA and NIAAA. With the formation of NISUAD these advances can continue to grow.

1. INSTITUTIONALIZE A ROLE FOR BEHAVIORAL RESEARCH.

This simple step will sustain scientists involved in basic and translational studies. Here, we mean developing RFAs, RFPs and other funding opportunities for basic and translational behavioral research, and cultivating program officers and study sections with expertise in behavioral science. Without such an institutional commitment behavioral research will be in danger. In fact, the diminished support for basic behavioral research by NSF and NIMH is a serious threat to the sustainability of a field that has made important theoretical, methodological, and translational contributions to the investigation of addiction. This presents an opportunity for NISUAD to become a major influence. NIDA and NIAAA benefited enormously by the research conducted by behavioral scientists, and so will NISUAD if it supports basic research.

2. IDENTIFY BASIC AND TRANSLATIONAL BEHAVIORAL RESEARCH AS A PRIORITY. This will improve our understanding of all stages of the addiction cycle and in the design of intervention strategies to break this cycle. The development of a substance abuse disorder, its prevention and treatment, and the sustainability of the benefits of treatment are all, in essence, behavioral problems. Any public health effort aimed at the treatment or prevention of substance abuse will include behavioral principles as a central component. Yet our understanding of these principles, and their translation, remains incomplete.

First, the core symptoms of pathological gambling are conceptually similar to features of substance use disorders. According to the DSM-IV, “the essential feature of Pathological Gambling” is “persistent and recurrent maladaptive gambling behavior …that disrupts personal, family, or vocational pursuits” (APA, 2000). Symptoms include withdrawal when attempting to reduce or stop gambling; preoccupation with gambling; and need to gamble increasing amounts to achieve desired mood.

Second, there is an abundant amount of behavioral, epidemiological and neuroscience data that empirically support similarities between pathological gambling and substance use disorders. Examples: a) based on data from the National Comorbidity Survey Replication, the onset and persistence of pathological gambling is predicted by prior DSM-IV addiction-related disorders, including impulse-control and substance use disorders (Kessler et al., 2008); b) brain imaging studies and neurochemical tests have made a “strong case that [gambling] activates the reward system in much the same way that a drug does” (Holden, 2010); and c) pathological gamblers report cravings and other addiction-related behaviors and in response to gambling stimuli that are analogous to signs and symptoms displayed by individuals with a substance dependence disorder, (e.g., Potenza, Leung, Blumberg, 2003; Breiter, Aharon, Kahneman, Dale, & Shizgal, 2001).

Third, this body of research has persuaded the APA’s DSM-5 task force to reclassify pathological gambling as an addictive disorder. As noted by Professor Charles O'Brien, M.D., of the University of Pennsylvania, the chair of the addictions work group for DSM-V, the commonalities of pathological gambling with other addictive disorders warrant its inclusion with these disorders, including substance use disorders, in the revised DSM system.

Fourth, whereas pathological gambling is a relatively low base rate disorder In the United States (the prevalence of lifetime problem or “at-risk” gambling is 2% and lifetime pathological gambling is 0.6%; Kessler et al. 2008), conservative estimates of its prevalence is much higher in subpopulations, such as youth and minorities (Petry, 2004).

Alcohol abuse and its myriad medical and social consequences must not be ignored or obscured under the topic of addiction. The two problems are often, though not always, distinct.

Administrative reorganization should not detract from the progress of science. How can the NIH possibly undertake this administrative burden as we face sequestration of 8-10%. Please don't spend vital research monies on administrative reorganization. NIH should ask congress for a large budget increase to accomplish this reorganization in the best public interest.

I would like to emphasize three other areas that I believe is worthy of consideration by NIH for emphasis by the proposed new institute:

1) Integrative Neuroscience “systems” approach in longitudinal studies of self-administration 2) The role of stress in alcohol addiction 3) Computational social neuroscience in pharmacotherapy development

The role of stress in alcohol addiction: A sustained effort is needed to disentangle stress and its role as a leading risk factor in the third largest preventable death in the United States. A comprehensive approach and investigation of pituitary, adrenal, gonadal, hematological and hepatic sources of cytokines, neuroactive steroids and other endocrine stress factors appear to be involved in this co-morbidity. Our body of knowledge is far too underdeveloped in this area, thus my suggestion that alcohol remain as a single factor, rather than a co-factor with another drug, for further research in this area.

Computational social neuroscience in pharmacotherapy development: Social factors may be a large reason why potential pharmacotherapies show promise in animal models but fail to have efficacy when transferred to the clinical population. A concerted effort in computational social neuroscience is needed to identify social constraint on addictive behaviors, how the constraint is lost in the addiction process, and the interaction between pharmacotherapies and social outcomes in predicting the efficacy of establishing abstinence. Specifically, the development of computer engineering is needed to continuously capture and remotely annotate social behaviors to identify the dynamic behavior of individuals in a social group and their reciprocal interactions as well as integrate their pattern of drug use. Animals allow the degree of control necessary to develop these computer programs and to assess patterns of drug use and their consequences on a real-time basis.

Addiction and abilities to quit are both likely to be driven by substantial genetic influences that contribute about half to individual differences in these phenotypes. Understanding the molecular genetic basis of these phenotypes therefore provides major work for the portfolio of NISUAD. It is not clear that any single approach will provide the optimal route to this understanding. Integration efforts should thus encourage pursuit of a number of independent approaches to this key aspect of addiction, should discourage concentration of control of this work and should provide institutional disincentives for organizational structures that act to limit responsible molecular genetic studies and analyses to single or few approaches.

1) History and several initial signs appear to point toward possible restriction of the diversity of human genetic approaches likely to be allowed or encouraged by NISUAD. These include the following:

There has been a longstanding large investment in a single extramural molecular genetics consortium by NIAAA (COGA) that has resulted in little diversity in extramurally-funded work on human genetics of alcoholism.

NIDA now funnels all extramural research with a molecular genetic component through a single unique prereview/postreview entity. An acting division chief chairs a committee and thus acts as a single de facto “decider” for any genetics research that can pass to the NIDA director and council. NIDA staff from other divisions believe that virtually no genetics work can be funded without approval of this individual, Dr Rutter.

Draft plans for NISUAD appear to call for a single intramural genetics “program”, raising the possibility that a single chief will function as effective “decider” for all intramural human genetics.

The human genetics opportunities for the NIDA intramural genetics program are currently sharply curtailed by administrative actions, reducing its ability to provide alternative (and apparently successful) approaches to complex genetics.

This lack of diversity has been accompanied by a very modest record of genetic accomplishments by linkage and GWAS approaches supported through COGA and the NIDA genetics extramural program.

2) There is now broad consensus that current consensus approaches to molecular genetics work poorly to identify many types of disease associated gene variants. Variants that display the “complex genetics” properties likely to be found in those that predispose to phenotypes of likely interest to NISUAD (including vulnerability to addiction, ability to quit and ability to respond to prevention strategies) have been poorly identified by current consensus approaches.

Features that make one current consensus approach (GWAS identification of single variants that provide Bonferroni-corrected levels of statistical significance) unlikely to succeed include: a) modest effect sizes of common variants for these common phenotypes; b) locus heterogeneity, and c) allelic heterogeneity. There are thus likely to be multiple variants at each of multiple genetic loci that contribute to each of these phenotypes, as well as others of interest re addiction. These features of genetic architecture are also likely to render resequencing data difficult to interpret.

Attempts to gain nominal power by aggregating samples from a variety of collection sites have provided evidence for large sample to sample variations. Principal components analyses of ARRA-funded dbGAP samples for addiction, for example, provide large components based on site of sample collection that are likely to mask many bona fide addiction related variants that are present at different frequencies with the differing genetic backgrounds sampled at different sites.

Consensus strategies for circumventing this problem include seeking rarer variants with greater effects in exome or genome-wide resequencing efforts, focus on variants that alter the “ADME” pharmacokinetic/pharmacodynamic properties of addictive substances, focus on variants in drug “receptors”, and renewed interest in candidate genes expressed in brain reward pathways modulated by addictive substances.

It is thus possible to focus large amounts of effort on single programs supporting resequencing of samples that have been studied in GWAS efforts, as suggested by recent NIDA RFAs, without addressing the underlying problems that lack of support for diversity in molecular genetic approaches and analyses has provided for the field.

3) The current state of science and general organizational principles both cry out for systematic support of a more diverse set of approaches to a) identification of the genes (and other chromosomal regions) that contain variants that contribute to individual differences in addiction, quitting, and prevention responses, b) understanding the ways in which these sequence differences change the brain or other organs, and c) understanding the ways in which these alterations alter addiction-relevant phenotypes.

This letter suggests that the results from Management Review committee integration process should provide a clear mandate for diversity, as well as appropriate scope, for genetics efforts of NISUAD.

In particular:

a) Centralized mandatory review channels in this field should be discouraged as NISUAD is established. Centralized programs should be informational, providing information for staff from all NISUAD branches and divisions about the range of possible useful practices as well as the dominant approaches. If there is any program established with de facto centralized mandatory funding approval authorities, it should be set up with strict sunsetting provisions (eg for 1 – 2 years at most).

b) Any “COGA-like” structure or centralized review process (such as the one currently maintained by NIDA) should not be encouraged, especially when its risks to diversity are at least as great as its benefits in providing scale. The risks for central NIDA review of extramural genetics by essentially, a single official (even a successful one) now appear to strongly outweigh the possible benefits of increased diversity in the NIDA genetics portfolio. The current central review process should be converted to a nonreview repository for information to aid other NIDA extramural program areas in optimizing their genetics portfolios, in ways that should include optimization of their diversity.

c) The diversity in human genetics approaches possible in the proposed Rockville and Baltimore campus intramural structure should be emphasized, with encouragement of better support for human genetics programs by established groups on both campuses and addition of staff. Sharing resources can be aided by establishment of incentives that do not mandate uniform approaches to human genetics of addiction-related phenotypes.

d) More laboratories and investigators should be encouraged to use genetic data, including transgenic animal models, to augment the translational utility of human molecular genetic results and increase the diversity of approaches to translating this data to improved understanding.

e) More clinical investigators should be encouraged to collect and use genetic data, to augment the possible T1 and T2 translation of these findings into other diverse areas relevant to addiction.

The founding of NISUAD provides an opportunity to break from the prior large influences exerted by relatively few investigators and administrators on centralized review of genetics protocols and concentration of resources in few samples and analytic approaches.

NISUAD’s promotion of diversity in its human genetic portfolio will be likely to pay substantial dividends. It is indeed ironic that genetics, a field that studies diversity, should need to be reminded of the benefits that diversity provides, especially in areas in which heavy concentration of resources in few hands have provided only modest benefits to date. The alternative, concentration of centralized control of genetic studies in few hands and further limitation of the diversity of approaches to the complex problems raised by addiction genetics, would appear not to allow NISUAD to optimally apply the power of human genetics for understanding addiction, its treatment and its prevention.

There are other agencies that fund research on impaired driving prevention (namely the National Highway Traffic Safety Administration, or NHTSA). NHTSA sponsors some extremely important work in this area, but it is not sufficient for there to be real advancements in harm reduction. NIH support for impaired-driving research is essential because: (a) NHTSA does not support researcher-initiated projects, thus there is limited opportunity for innovation; (b) NHTSA requirements that research involving surveys first receives clearance from the Office of Management and Budget greatly reduces the type of research that can be conducted and the cost-efficiency of that research; and (c) NHTSA does not support peer-review publication of research results until government reports are approved; there is a large volume of relevant-research not made available to the scientific community because it is not identified as a priority by NHTSA.

In general, given that over half of the harm caused by alcohol and drugs is behavioral, there needs to be sufficient support for behavioral research in the area.

Fortunately, the death, injury and damage caused by alcohol-impaired driving are all entirely preventable. From 1982 to 1997, the United States experienced a dramatic reduction in alcohol-related fatalities. Rates have been stable ever since, and in some places reverted upwards, but we can begin to reduce these numbers once again. The problem of impaired driving is surmountable. There are ways to cut into the tragic number of deaths and injuries caused by impaired driving. Rigorous multidisciplinary research that emphasizes the translation of scientific knowledge into real-world solutions is an essential step to realizing a future of safer highways and roads, and a healthier American public.

I would like to highlight and extend a couple of the areas identified in the RFI that I believe are important in maximizing the effects of addiction research on public health. First, as noted in the RFI, funding efforts to prevent substance abuse in adolescents and young adults is obviously important. At the same time, additional basic research on the predictors of substance use and transitions to abuse and dependence among young people is necessary in order to make those prevention programs targeted to the most vulnerable youth and make them as effective as possible. Therefore, I would urge the new institute to also focus on this foundational research—the development of substance use and addiction in youth--in addition to actual prevention programs.

Second, comorbidity with other psychiatric disorders is mentioned in relation to tobacco use, but I would suggest that examinations of how other psychiatric disorders relate to the development, maintenance, and treatment efficacy of all addictive disorders is crucial for our understanding (and prevention and treatment) of addiction in general. We know that these comorbidities exist, yet our understanding of how other psychiatric disorders influence, or are influenced by, addictive disorders is in its infancy. It seems that increasing our understanding of this is crucial to successful prevention and intervention.

Finally, I believe that funding research on the genetics of addictive disorders, particularly gene-by-environment interactions, is likely to yield useful information that can be applied to the prevention and treatment of these disorders. Methodological advances in this area have facilitated sophisticated research that could yield significant advances in treatment and prevention efforts, and continuing on this path has the potential to have a significant impact.

World Health Organization (2009). Global health risks: Mortality and burden of disease attributable to selected major risks [Accessed: 2011-01-24. Archived by WebCite® at http://www.webcitation.org/5vzJ7a2NV]. Geneva: WHO.

World Health Organization (2010). Global strategy to reduce the harmful effects of alcohol. Geneva: WHO. http://www.who.int/substance_abuse/alcstratenglishfinal.pdf

2. Establish a Prevention Research Branch. Establishment of a new combined institute should be used as an opportunity to build from and strengthen NIH’s prevention portfolio. This can most effectively occur when a branch of the institute is charged with this priority. We strongly endorse that the new institute include prevention explicitly in the mission and elevate prevention to a research branch with funding allocated to alcohol and drug abuse prevention research at least equal to, and ideally greater than, the sum of the current levels at NIAAA and NIDA.

3. Alleviate the Bottleneck for Treatments to Move from Bench to Bedside to Communities. To foster innovation and transformation in the next generation of prevention research, we recommend the expansion of Type 2 translational research, including studies of the adoption, implementation, and sustainability of tested and efficacious programs, policies, and practices in communities, services settings, and populations. This research would ensure that existing knowledge generated from basic research and randomized controlled trials results in reductions in the incidence and prevalence of alcohol and drug abuse and addiction and associated problems at a population level through implementation of effective programs in community settings.

4. Greater Emphasis on Environmental and Contextual Influences in the Scientific Strategic Plan. Recognizing the importance of biological science in understanding alcohol misuse or drug abuse and addictions, the current list of priorities underemphasizes the critical role of social and behavioral science in understanding and addressing these problems. Research funded by NIDA and NIAAA suggests a strong role of the environment on the initiation of drug and alcohol abuse and addiction behaviors, and that socio-cultural environments (e.g., policy, peers, family, communities) play pivotal roles in the initiation of, maintenance of, and desistence from drug use, abuse, and dependence. Certainly there is an interplay of environmental and biological influences in the development of addiction, however, to downplay the social, cultural, and psychological aspects of drug use is a fundamental miss that will severely weaken efforts at prevention and treatment. Continued emphasis on environmental and contextual influences in basic science and intervention research will ultimately help reduce the budget of substance use, abuse, and addiction-related disorders.

5. Pursue the Recommendations of the IOM Report. The report on prevention from the National Research Council and the Institute of Medicine (IOM) documents the substantial progress that has been made in prevention research since the IOM’s previous report on this topic in 1994. A substantial portion of the research cited in the new report was funded by NIDA. There are a number of recommendations from that committee that are important to pursue: (1) continuing the course of rigorous research both on specific and general risk factors and on protective factors that weaken or strengthen, respectively, age-appropriate competencies; (2) studying dissemination strategies; and (3) creating new research linkages with neuroscience.

We also need to understand what the factors are that contribute to initiating alcohol and drug use after a period of sustained recovery. How often do people start using again across the life cycle of recovery? Are there points of vulnerability associated with age, primary drug(s), recovery pathway, gender, race/ethnicity, sexual orientation, or presence of co-occurring medical/mental health disorders? Are there critical transition points from early recovery to sustained recovery and from recovery maintenance to enhanced quality of life in recovery that increased risk of relapse? Does the availability and use of peer and other recovery supports, recovery institutions such as recovery community centers, recovery schools, recovery-oriented employers, recovery residences, alcohol- and drug-free recreational activities, affect a person’s ability to sustain recovery for the long haul?

The impact of research in this area would be of great interest to the public and policymakers – it would demonstrate the reality and pathways to recovery to a public that is skeptical about the ability of loved ones, friends and co-workers to recover from addiction to alcohol and other drugs. Research that found that recovery from addiction was a contributing factor to lowering recidivism rates for people re-entering communities from incarceration could assist policymakers in making decisions about policy and funding priorities.

It should also be of great interest to scientists seeking to understand the management of this chronic health condition – mainstreaming addiction recovery research with research on other manageable chronic health conditions and providing information about the solutions to a problem that has been well researched and documented.

B). Recovery patterns and experiences for specific groups of people including young people, women, and parents in recovery. This research area should be of great interest to policymakers as well as to the public and scientists. The earlier that a person identifies and embarks on his or her pathway to long-term recovery, the better in terms of personal health and wellbeing, family and community health. The costs of addiction are dramatically reduced as well; benefiting taxpayers and communities.

Using young people as an example, some of the questions that could be asked include: •What is the prevalence of recovery among young people; is it increasing, decreasing? •Are there predictable stages of recovery for young people? •Do the recovery rates of young people differ by gender, ethnicity, drug choice or other variables? •Does a family history of recovery affect a young person and/or other family members’ recovery? •Do young people whose families are affected by ongoing alcohol and other drug problems have better opportunities for sustained recovery if they sever family ties? •How can parents, other family members and significant people in a young person’s life best help him or her to initiate and sustain recovery over a lifetime? •What are the effects of post-treatment monitoring, recovery coaching and assertive linkage to communities of recovery on long-term recovery outcomes for young people? Are they different than for adults? For parents in recovery, some questions that could be asked include:•If a son or daughter is at increased risk of developing an alcohol or drug problem because they and one or both parents share a family history of such problems, do the children have less risk of developing problems if the parent is in long-term recovery? •If one or more children were to develop an alcohol or drug problem, are their prospects of recovery better because of the parents’ recovery? •What strategies of prevention and early intervention can specifically lower the risks of children of recovering parents developing alcohol and other drug problems at an early stage? What effect does the participation of a family member in specialty sector addiction treatment and/or recovery mutual aid groups have on the recovery prospects of other family members? •What changes should a person anticipate in early recovery in relationships with children and other family members? •What does it mean when parents who have lost custody or left their children during their active addiction seek to re-establish contact with their children? Will this harm or benefit the child and if so, when and how? •What evidence-based models are available for peer-based support for parents in recovery, e.g., parenting guides/sponsors?

C). Communities of Recovery. How does the level and degree of exposure to communities of recovery and recovery-oriented communities affect a person’s individual and family member recovery? Do community supports such as faith-based organizations, opportunities for community activities/advocacy strengthen recovery and affect community wellbeing? What is the impact of having multiple housing options available for people in early or long-term recovery available mean to building recovery-oriented communities? Are there specific activities, events or developmental issues that pose significant challenges to recovery and community health? If so, what works to support recovery and community health?

D). Recovery self-management. Growing numbers of people seeking addiction recovery are developing recovery plans that they modify over time to reflect their progress in reaching recovery goals. Does it make a difference if a person develops his or her own recovery plan in a community or clinical setting compared with the development of a treatment plan by a clinician?

E). Peer and other recovery supports. Non-clinical recovery support services are offering people seeking or in recovery new services based in the community. These services can be used alone, in combination with mutual aid and/or professional treatment. What are their effects on the person seeking recovery as well as the person providing the service?

F). Recovery support institutions and service roles. Over the last ten years a growing number of recovery community organizations have pioneered the development and delivery of peer recovery support services for people in or seeking recovery from addiction to alcohol or other drugs. These organizations provide services in a variety of diverse settings, including recovery community centers and recovery residences, as well as host of other settings outside of the recovery community including jails and prisons and medical settings. Peer recovery support services and organizations that provide them have been operating virtually unnoticed until the emergence of the health reform-related focus on prevention and wellness, an emphasis that highlights recovery-oriented systems of care and implementation planning.

These nonclinical services often assist individuals and families and include peer recovery coaching, recovery community centers, recovery residences, job readiness programs, financial management training, educational/ employment assistance, and telephone check-ups. These services are provided prior to, during, after or in lieu of treatment and other clinical services and support. The use of peer support is, by now, a common practice in many fields. While professionals treating chronic illnesses are often knowledgeable about peer services, there is still limited awareness among individuals and families. In today’s medical world, peer support is recognized as a valuable adjunct to professional medical and social interventions. Improved outcomes are particularly notable when peer support services are provided to people with chronic conditions that require long-term self-management. The peer recovery support services offered by recovery community organizations and others are supported by a long, well-documented, and replicated evidence-based tradition. Peer recovery support services hold promise as a vital link between systems that treat people with addiction in a clinical setting and the larger communities in which people seeking to achieve and sustain recovery live.

There is a robust body of research on the value and effectiveness of peer supports for a number of chronic health conditions such as diabetes, cancer, obesity, HIV/AIDS and mental illness. This research has identified the value of services delivered by peers at the community level and the usefulness of a wide variety of social and other supports.

There has been limited research on the effectiveness of addiction peer recovery support services, mostly focused on recovery residences (housing). While there is a good start on this research, there is very little research on other recovery support institutions such as recovery schools, recovery community organizations, recovery community centers, recovery industries or recovery ministries. And there is next to no research on the emerging peer and other recovery support service roles of recovery coach and peer recovery support specialist.

G). The Neurobiology of Recovery NIDA’s studies of the brain should also focus on brain resilience and recovery. To what extent and how does the brain heal? How does long-term recovery affect this process?

NIAAA’s studies of the health impact of alcohol dependence should also focus on the health impact of recovery from addiction. To what extent and how does health improve? How does long-term recovery affect this process?

Thank you for the opportunity to provide input to this important effort.

As chronic smoking is highly comorbid with both alcohol and illicit substance abuse, and as different types of substances are abused together to achieve a desired effect, polydrug use research has wider practical utility than past research forced into one corner or the other due to the separate existence of an alcohol and a drug institute. Practical utility and clinical relevance is increased by studying the clinical reality today – that is polydrug use - and should be a main research focus of the newly proposed institute. It is time for a newly formed institute to serve the type of patient that is actually seen in the clinic today.

In the case of FASD at least, the causes and consequences of addiction are increasingly known to overlap. Alcohol addiction has long been known to run in families. This is not just because children learn from the example set by their parents. FASD children often grow to become alcoholics and to abuse other drugs, even if they are raised in foster families. Animal studies also now show that animals that are exposed to ethanol during fetal life, exhibit a preference for ethanol in adulthood.

We are becoming aware that fetal experience predisposes the adult to disease, but we do not know the full extent of the problem. We do not understand how or why prenatal alcohol exposure predisposes individuals towards drug abuse. Does prenatal alcohol directly reprogram brain addiction circuits or does it program the endocrine system, or the immune system, or the hypothalamic circadian pacemaker, or the limbic circuitry, or learning and memory circuits, or……..? All of these factors and more could influence the development of addiction. The reality is that we know so little about the fetal basis of addiction that we can ill afford to cut off this avenue of research.

Finally, addiction (and alcoholism) has a multi-generational component. Alcoholism may run in families because of genetic factors. However, increasingly, experimental data suggests that epigenetics can account for the inter-generational passage of acquired traits. Epigenetics could influence the emergence of multi-generational addiction behaviors as well. A mother who drinks during pregnancy may influence the drug preference and addiction propensity of at least two generations (if not more) of offspring. The epigenetic contribution to addiction cannot be divorced from the developmental effects of alcohol abuse.

By separating cause from consequence, you run the risk of creating new silos where none exist. Some research into the developmental and inter-generational causes of addiction will simply not get done, because there will be no single agency with the responsibility to foster the growth of research in these areas. I therefore urge you to include both the causes and consequences of addiction within the portfolio of the new addiction institute.

Expand the Research Focus on Policy/Environmental Strategies We encourage the new institute to continue the leadership NIAAA has taken to fund policy/environmental strategy research focusing on preventing alcohol abuse and related harms (e.g., research on alcohol taxes). Policies and environmental strategies are used to shift political, social and economic conditions that contribute to substance use and abuse. These are community-level interventions that aim to achieve population-level benefits for the entire community. More research is needed to continue to build the intervention base in this area. We also urge the institute to take a strong leadership position by funding a large portfolio of policy and environmental research on illicit drugs. There is a paucity of such research; however, there are many lessons to be learned from alcohol and tobacco research that would be important to test out in drug prevention. Practitioners critically need this information to guide their work.

Focus on Risk Factors Specific to Substance Abuse While there are shared risk factors for various problems, there are also some that are specific to substance abuse prevention that need to be attuned to in research and practice in order to have a population-level impact on alcohol and drugs. Particularly, we cannot lose a research focus on investigating additional strategies and interventions that impact the access and availability of alcohol and drugs. We must continue to focus research efforts on risk factors explicit to ATOD use/abuse. A sole focus on shared risk factors will miss out on important levers contributing to substance abuse in our communities.

Fund Participatory Research We also encourage the new institute to make more investments into studies using participatory methods. Community-based participatory research (CBPR) is a collaborative approach to research that engages community members such as Community Connections, and researchers as equal partners in all phases of the research process (Israel, Schulz, Parker, & Becker, 1998; Foster-Fishman, 2009). CBPR more appropriately responds to the needs of communities because it engages community members in defining the problem, selecting the solutions, controlling the implementation and owning the knowledge generation process. An understanding of the community context is imperative in solving local problems and the strategies and methods selected by the community are more likely to fit the local context (Foster-Fishman, 2009; Katz, 2004). Additionally CBPR supports Type II Translational Research by making research and action more culturally competent, relevant, and useful (Foster-Fishman, 2009). This approach to research answers questions that fit practitioner needs and take into consideration more of the factors and conditions in which interventions are implemented in real world setting; hence interventions that come out of CBPR studies are more likely to have buy-in and utility to the community.

Increase Community-Based Research Expertise on Review Panels The makeup of the review committees needs to be less clinically oriented for prevention grants. Prevention research, particularly those that are community-based, require review committees comprised of members who are experts on this type of research. Panel members should understand the particular challenges and benefits for research conducted in community settings, be familiar with collaborative/participatory methods and the benefits these approaches can add to research quality, and understand the usefulness and value of alternative methods to RCTs that may be more culturally competent, ethical and appropriate for certain settings and research questions. As someone that has served on multiple review committees, community based participation is essential to guiding others in understanding how communities truly incorporate others into solving the issues where it matters most…at the community level.

Support More Research on Comprehensive, Community-based Approaches to Substance Abuse Prevention Complex community health problems, like substance use and abuse, require comprehensive, collaborative solutions in order to achieve benefit for the entire community or targeted population. “As the field of prevention has matured, it has been recognized that any single strategy is unlikely to succeed and a reinforcing set of strategies has the greatest potential to reduce use” (Johnson et al., 2007, p. 229). Substance use and abuse is influenced at multiple levels and as such interventions must be broad-based, comprehensive and seek change at multiple levels (Bronfenbrenner, 1979; Sorensen, Emmons, Hunt & Johnston, 1998). The new Institute needs to focus research on these comprehensive, community-based approaches. In addition, research to guide practitioner use of these strategies and how to combine them in ways to achieve maximum benefit for the smallest cost are also needed. Additionally, while there is much focus on single interventions and their impact, more research is needed on the synergy that occurs when a comprehensive set of strategies working at multiple levels of influence are implemented.

Most important, the policies and interventions that have driven most of this decline have been population-level interventions that have little to do with the fact that nicotine is addictive, the pharmacology of nicotine addiction, or the treatment of that addiction. Rather, this progress has been made under the broader agenda of cancer and heart and lung disease prevention and control by understanding the social determinants of smoking behavior, the effectiveness of population-based interventions (such as smokefree policies, tobacco taxation, media campaigns and smoking in the movies) as well as learning how to counter efforts by the tobacco industry to block implementation of effective interventions. These are all areas that the NCI Division of Cancer Control and Population Sciences, through its Tobacco Control Research Branch, have stimulated and supported for many years.

In addition, in recent years, the National Heart, Lung and Blood Institute has developed an interest in smoking treatment among hospitalized smokers and the effects of secondhand smoke on the cardiovascular system. The location of this work in NHLBI has been important for engaging the cardiovascular community in issues of smoking and tobacco treatment and prevention, something that has been sorely needed for a long time.

The relative importance of addiction (and related) research to dealing with the overall tobacco problem is illustrated by the volume of publications in different areas. Searching PubMed on 9 May 2012 yielded the following results:

(tobacco or smok*) and addiction: 5,390 papers (tobacco or smok*) and cancer: 44,009 papers (tobacco or smok*) and (heart or lung or blood): 84,991 papers

This broad distribution of work between relevant NIH Institutes should be maintained and encouraged.

It is also important to note that, while tobacco work is spread across NIH, there has been good cooperation between the existing institutes, particularly NCI and NIDA (where almost all addiction and nicotine treatment work is already located). Rather than trying to consolidate all or most tobacco research in the new institute, the kind of cross-institute collaboration that has already been so successful should be continued and rewarded.

I am co-director of the UCSF Helen Diller Family Comprehensive Cancer Center’s Tobacco Program. It has been a long fight to integrate tobacco control into the cancer center’s basic biological and clinical programs, but we are now making progress. Shifting the tobacco control research portfolio out of NCI will create the appearance and reality of NCI walking away from tobacco. Worse, it will and send a strong message that NCI does not think that tobacco control research is a priority for cancer control.

This reorganization of NIH comes at a particularly sensitive time for tobacco control, given the release last year of Secretary Kathleen Sibelius’ “Ending the Tobacco Epidemic: A Tobacco Control Strategic Action Plan for the US Department of Health and Human Services.” Even a cursory review of this document will reveal that the work funded by and conducted at NCI provides much of the scientific foundation for this plan. NCI should be taking credit for this important contribution, not trying to move it to another institute.

I am particularly concerned that the proposed reorganization of tobacco control research will create heightened opportunities for the tobacco industry to shut down the kind of research and training that has made such a strong contribution to reducing smoking prevalence and consumption together with a wide range of cancers and other diseases. Even absent frank political interference, a major reorganization will almost certainly disrupt NIH’s tobacco control funding and activities at this crucial time.

Rather than concentrating all or most tobacco control research in the addictions institute, NIH should work to integrate tobacco into the full range of its programs. Tobacco kills more people through heart and vascular disease than cancer, yet NHLBI has had a very limited presence in tobacco control research.

I have also attached a letters on this subject that Dr. Frank McCormick, director of our Cancer Center, and I sent NIH Director Collins on this subject last year addressing these points.

In addition, I draw your attention to the editorial published in 2011 by leaders of the American Cancer Society, American Heart Association, American Lung Association, Campaign for Tobacco Free Kids, Legacy Foundation and Partnership for Prevention (Tobacco Control 2011;20:175e177, doi:10.1136/tc.2011.043968) that concluded, “As major organisations concerned with reducing the burden of tobacco-induced diseases we strongly advise the task force and Director Collins to leave existing tobacco research at NCI, NHLBI and the Fogarty International Center, with some flexibility regarding the transfer of research that is wholly focused on the dependence-producing properties of tobacco. Indeed, rather than removing tobacco research from these (and other relevant) institutes, they should be encouraged to strengthen and expand their efforts to a level commensurate with the risks tobacco imposes and the central contribution that reducing smoking and tobacco use has been demonstrated to have reducing the burden of cancer, heart, lung and other diseases.”

This is a sensible recommendation from organizations that represent an important element of NIH’s organized constituency in general and regarding tobacco in particular. Please carefully consider the practical effect on the research community and the ability of NIH to make an ongoing contribution to implementing the Department’s new Strategic Plan and see that there are no disruptions to NIH’s contribution to reducing the burden of tobacco-caused cancer and other diseases.