Full Text PA-95-076

MARIJUANA/CANNABIS ABUSE RESEARCH

NIH GUIDE, Volume 24, Number 26, July 21, 1995

PA NUMBER:  PA-95-076

P.T. 34

Keywords: 
  Addiction 
  Biomedical Research, Multidiscipl 
  Behavioral/Experimental Psychology 
  Drugs/Drug Abuse 


National Institute on Drug Abuse

PURPOSE

This program announcement encourages research across the broad area
of marijuana/cannabis abuse.  The abuse of marijuana is a significant
problem, shows little evidence of abatement, and may still be
increasing in scope.  Based on a review of information available and
the research supported by the National Institute on Drug Abuse
(NIDA), this program announcement identifies many areas of research
that are particularly in need of development.  Investigators from
many scientific disciplines are encouraged to apply either
individually (e.g., as individual projects) or collectively (e.g., as
a program project).

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This program
announcement, Marijuana/Cannabis Abuse Research, is related to
priority area of alcohol and other drugs.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, research institutions, units of
State and local governments, and eligible agencies of the Federal
government.  Applications from minority individuals and women are
encouraged.  Foreign institutions are not eligible for First
Independent Research Support and Transition (FIRST) (R29) Awards or
program project grants (P01).

MECHANISM OF SUPPORT

Support mechanisms are research project grants (R01), small grants
(R03), FIRST (R29) awards,  and program project grants (P01).
Because the nature and scope of the research proposed in this program
announcement may vary, it is anticipated the size of an award will
vary also.

RESEARCH OBJECTIVES

The term  "marijuana abuse" is used to describe a variety of drug
abuse behaviors that include the use of cannabis and its derivatives
in all forms and in combination with other drugs.

Research areas of interest include, but are limited to, the
following:

I.  Etiology: Genetic, Social, Cultural, Behavioral,Neurobiological,
and Environmental

Research is needed to determine the interactions of neurobiologic,
genetic, behavioral, social and cultural, and environmental factors
and processes in association with the initiation, continuation, and,
discontinuation of marijuana abuse and dependence in both cross
sectional and longitudinal designs.  Investigators are encouraged to
use a physiological, sociocultural and behavioral developmental
perspective in these studies, recognizing the differential impact of
factors at various stages of human development and the impact of
cannabis abuse at these different developmental stages.

Research opportunities exist to investigate the neurobiological bases
for the behavioral risk factors leading to the development of
marijuana abuse especially with respect to initiation, compulsive use
and dependence, and withdrawal.  Also, the elucidation of
biobehavioral factors involved in the discontinuation of marijuana
abuse is necessary to more fully understand the process of abuse for
this drug.  Studies could focus on the genetic and/or other
neurobiological factors contributing to drug-seeking behavior, as
well as other neurobiological correlates involved in placing an
individual at risk of initiating and maintaining marijuana use, and
in turn, leading to possible dependence.  Conversely, studies on the
neurobiological factors that might "protect" an individual from the
typical pathogenesis of drug addiction are important.

Also of particular importance are studies to examine the contribution
of the use of tobacco and alcohol and other possible early causal
determinants on the simultaneous or subsequent use of cannabis,
especially the changes that these substances might have on brain
systems leading to drug vulnerability.  Where possible, to examine
the contribution of marijuana use to the use of other both licit and
illicit substances.

Studies could focus on how such factors as lack of family support,
family violence, abuse and neglect, lack of positive role models,
poor parental supervision, parental drug use, breakdown of the
extended family system, association with peer groups and the
socioeconomic status as well as medical illnesses/disabilities (e.g.,
ADHD, ADD, and other psychiatric disorders) affect initiation,
continuation, and escalation of marijuana use among individuals,
particularly among children and adolescents.  Moreover, factors that
mitigate or protect against drug involvement should also be
considered for study.

Studies could also focus on cultural values and attitudes toward
marijuana use, acculturation related stress, or loss of cultural
identification of minority individuals, of the existence of
subcultures of marijuana use, crosscultural etiology (local, endemic
or worldwide).  In addition environmental factors such as drug
availability and distribution networks, recreational and employment
opportunities, negative social sanctioning and attitudes within
society, gangs, religion on the use of marijuana/cannabis should be
considered.

The impact of negative psychological, developmental, and psycho-
pathological factors, such as self-esteem, depression, aggressive
behavior, coping styles should be studied as they influence the use
of drugs.  Of particular interest are studies of factors that
establish resiliency and protection for children at high risk but who
do not abuse drugs such as marijuana.  Such studies might lead to the
early identification of those at risk of marijuana use or identify
motivating factors responsible for the cessation of marijuana use.

II.  Epidemiology

Studies are needed to provide a definitive understanding of the
patterns and prevalence of marijuana use through cross-sectional and
natural history methods among high-risk youth, school drop-outs, gang
members, children of drug users, and homeless youth.  Research is
needed to determine the prevalence of marijuana use among children,
adolescents and young adults in various settings including primary
care settings (HMOs, hospital-based and community-based clinics, and
emergency rooms), social service agencies, college campuses, etc..

Moreover, these studies should focus on the short- and long-term
social, behavioral, and health consequences of marijuana use on the
individual users, their families, and on the community.  The
interrelationship between marijuana abuse and other deviant behaviors
should be examined as well as school performance and attendance, the
dynamics associated with different consequences relative to marijuana
abuse, bases for endemic patterns of abuse and diminished use of
marijuana.  Furthermore, studies need to be conducted to assess
users' values, beliefs, and routines and their perceptions as to the
social, behavioral, and health consequences of their marijuana using
behaviors.

III.  Prevention Intervention

Marijuana abuse prevention intervention research scientifically
approaches the causes, onset and progression of marijuana use in
order to design, develop, and test theory-based prevention
interventions focused upon the individual, family, peer group, and
community (school, workplace, neighborhood).  These studies may focus
on intervening in early childhood behaviors and characteristics found
to be associated with high risk users and abusers such as attention
deficit disorders, conduct disorders, hyperactivity, and learning
deficits.

Primary goals of intervention research are to develop a
scientifically-sound knowledge base concerning the effectiveness of
marijuana use and abuse prevention policies and programs, and develop
and test innovative intervention strategies that can be delivered in
a variety of settings to include the school, communities, and the
workplace.  Special settings such as school based health clinics and
in primary care settings would require methods for the detection of
children who are at risk of drug abuse.  Randomized controlled and
quasi-experimental designs are encouraged.  Prevention intervention
research should focus on one of three strategies: universal (which
focus on populations not identified on the basis of individual risk
to drug use/abuse), selective (which target populations at risk) and,
indicated (which target groups who have detectable signs, symptoms or
behaviors indicative of drug use).  Methodological studies are
encouraged to develop valid and reliable markers and measures of key
variables; unified approaches to the collection and utilization of
both qualitative and quantitative data; accurate measures of both
cost and benefits of prevention programming; data analysis procedures
suitable to measure changes in key variables over time; and,
innovative techniques to assess diffusion of preventive practices.

IV.  Treatment

Treatment of marijuana abuse and dependence has not been adequately
studied.  Only a few therapies have been adapted for treating
marijuana abuse and dependence and studied for efficacy mostly in
adults.  Therefore, investigators should give increased attention to
developing new strategies and improving existing therapeutic
approaches.  Studies should focus on treatment designed specifically
for primary marijuana abuse or dependence as well as dependence
secondary to alcohol or other drug abuse or dependence.  Subgroups of
interest include children and adolescents, and women who are
pregnant, individuals with co-occurring medical and/or mental
disorders, and those involved in criminal activities.  Investigators
should scientifically study the efficacy of behavioral therapies
including counseling, psychotherapy, relapse prevention, family and
group therapy, social skills training, as approaches for the
treatment of marijuana abuse and dependency and associated
correlative health and social consequences.  Because many marijuana
users do not want treatment or do not believe they need to control
their marijuana consumption, increased attention should be given to
developing therapies that focus on individuals that incorporate
precontemplation and contemplation stages of change as well as
developing therapies for the action and maintenance stages as well as
stepped care models of treatment.  Attention should be given to
therapies for use in settings distinct from standard drug abuse
treatment programs such as primary health care or office-based mental
health settings.

Outreach strategies, alone and in combination with case management,
should be examined in terms of enlisting and maintaining marijuana
abusers in treatment and rehabilitation programs.  Related research
might also examine the form and extent to which professional, legal,
economic, and administrative factors relate to the accessibility and
effectiveness of therapeutic programs and supportive services that
are already available.  Additionally, research should be directed
toward developing screening and assessment techniques that would
include biological, self-report and other diagnostic tools related to
criteria specific to marijuana abuse.  Other studies should identify
pre-existing and co-existing neurobiological, psychosocial and
environmental factors that significantly impact on treatment
outcomes.

Furthermore, additional research is needed on the prevalence of
marijuana use among clients in treatment for other drugs of abuse and
the role marijuana abuse plays on progress in treatment and in
relapse after treatment.

V. Clinical and Basic Science

Short- and long-term sequelae have been correlated with marijuana
abuse, including cognitive impairment, cardiac disease, pulmonary
disorders, endocrine and reproductive disorders, as well as cancer.
However, many of these observations are based on case reports or
studies that have methodological limitations.  Further research needs
to evaluate medical sequelae and neuropsychological/neuropsychiatric
and neurobiological consequences of marijuana abuse incorporating
epidemiologic, clinical and natural history approaches; evaluate
associated learning difficulties and other consequences of cognitive
impairment as well as alteration in motivation as both a cause and a
consequence of marijuana use, and clarify the role of psychiatric
disorders as both a cause and a consequence of marijuana abuse.  The
impact of duration of use and chronicity of use also needs to be
clarified.

Opportunities exist to study the neurobiological effects of marijuana
and its active component, delta-9- tetrahydrocannabinol, on the brain
anatomy, physiology and chemistry.  Brain imaging and other
noninvasive techniques allow for the direct study of marijuana abuse
on specific brain systems, and direct correlations now can be made
between marijuana's effects on the brain and behavioral changes.
Particularly important are human studies assessing the effects of
chronic, long-term marijuana use on structure and function of the
brain.

HIV infection, sexually transmitted diseases, tuberculosis, and
hepatic disease, (e.g., hepatitis B, C) are prevalent among illicit
drug abusers and have been linked with both needle use and risky
sexual practices.  As drug abusers have polydrug patterns that often
include marijuana, investigations of relationships between marijuana
abuse and the transmission and pathophysiology of these diseases are
needed.  There is a strong interest in assessing the association of
marijuana use, particularly chronic use, and impaired immune
function.  Studies are needed to examine chronic use of marijuana and
exacerbation of medical and health consequences in immune-compromised
individuals such as in cases of HIV infection, cancer, and organ
transplantation.

Animal studies of marijuana consequences should attempt to model
human exposure and should include studies of marijuana smoke
(containing many different constituent compounds including
cannabinoids and tars) as well as drug interactions.  Given that
marijuana use is frequently accompanied by alcohol use, studies on
this interaction are particularly encouraged.  Studies in animals
should evaluate potential adverse consequences of marijuana exposure
such as effects on fetal development, pulmonary function, immune
function, and carcinogenicity.  Animal research should explore CNS
effects of both acute and chronic exposure to marijuana and related
compounds, including THC and anandamide.  These studies should
identify the neural pathways, receptor subtypes mediating
cannabinomimetic effects, and mechanism of action.  The biological
and environmental factors contributing to vulnerability to marijuana
abuse should also be explored in animal and human laboratory studies.

Studies of interest also include parallel animal and human behavioral
and biological evaluations of the effects of marijuana exposure on
learning, memory, and performance across the life span.  This
includes developmentally appropriate measures of cognitive and
performance effects of acute and chronic marijuana use in human and
animal studies on learning and memory, motor function, and
perception.  Additional behavioral developmental studies should
address effects on motivational and emotional states as well as
social interaction.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations) which
have been in effect since 1990. The new policy contains some new
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research", which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513), and reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume
23, Number 11.

Investigators may obtain copies from these sources or from the
program staff or contact person listed under INQUIRIES.  Program
staff may also provide additional relevant information concerning the
policy.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  The receipt dates for
applications for AIDS-related research are found in the PHS 398 (rev.
5/95) instructions.  Application kits are available at most
institutional offices of sponsored research and from the Office of
Grant Information, Division of Research Grants, National Institutes
of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD
20892-7762, telephone (301) 710-0267.  The title and number of the
program announcement must be typed in Section 2a on the face page of
the application.

FIRST (R29) award applications must include at least three sealed
letters of reference attached to the face page of the original
application.  FIRST (R29) award applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or principal investigator could be included
with the application.

The completed original application and five legible copies must be
sent or delivered to:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier/overnight service)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public
Health Service referral guidelines.  Applications that are complete
will be reviewed for scientific and technical merit by a peer review
group convened in accordance with the standard NIH peer review
procedures.  As part of the initial merit review, all applications
will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be
discussed, assigned a priority score and receive a second level
review by the appropriate national advisory council.

Review Criteria

o  scientific, technical, or clinical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

The initial review group will also examine the provisions for the
protection of human and animal subjects, and the safety of the
research environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding
decisions:  quality of proposed project as determined by peer review,
availability of funds, and program priority.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Lynda Erinoff, Ph.D.
Division of Basic Research
National Institute on Drug Abuse
Parklawn Building, Room 10A20
5600 Fishers Lane
Rockville, MD  20857
Telephone:  (301) 443-1263
Email:  LERINOFF@AOADA.SSW.DHHS.GOV

Direct inquiries regarding fiscal matters to:

Dr. Gary Fleming
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-55
Rockville, MD  20857
Telephone:  (301) 443-6710
Email:  gf6s@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.279.  Awards are made under authorization of the
Public Health Service Act Section 301 (42 USC 241) and administered
under PHS grants policies and Federal Regulations at Title 42 CFR
Part 52, "Grants for Research Projects,"  Title 45 CFR part 74 & 92,
"Administration of Grants," and 45 CFR Part 46, "Protection of Human
Subjects."  Title 42 CFR Part 2 "Confidentiality of Alcohol and Drug
Abuse Patient Records" may also be applicable to these awards.  This
program is not subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.  Sections
of the Code of Federal Regulations are available in booklet form from
the U.S. Government Printing Office.  Awards must be administered in
accordance with the PHS Grants Policy Statement, (rev. 4/94), which
may be available from your office of sponsored research.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In
addition Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a
facility) in which regular or routine education, library, day care,
health care or early childhood development services are provided to
children.  This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

.

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