Notice of Special Interest (NOSI): Administrative Supplements for research on fentanyl and derivatives
Notice Number:

Key Dates

Release Date:

March 25, 2021

First Available Due Date:
April 01, 2021
Expiration Date:
April 01, 2022

Related Announcements

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

Issued by

National Institute on Drug Abuse (NIDA)


NIDA is issuing this Notice of Special Interest (NOSI) to highlight the urgent need for research on fentanyl and derivatives. NIDA is interested in supporting research to understand the public health impact, clinical characteristics, and treatment of fentanyl addiction and overdose and how they differ from liabilities associated with morphinan-opioids. NIDA is especially interested in research examining the risks and outcomes of fentanyl addiction and overdose.


Centers for Disease Control and Prevention (CDC) data show that fentanyl-related mortalities have rapidly increased recently. In 2013 fentanyl-related deaths were half those of heroin (1 death per 100,000 population), but by 2020 fentanyl-linked deaths have increased 10-fold and double those involving heroin. Fentanyl was initially used as a “cutting agent” with other opioids (e.g., heroin, counterfeit prescription medications) but the high potency makes it desirable to users in its own right and today fentanyl is also commonly found in seized stimulants and “club drugs”. The high potency and increased distribution of fentanyl together contribute to its lethality but there are also other characteristics that affect risk. Fentanyl is structurally different from morphinan-opioids and preferentially partitions into fat-rich tissues such as brain. This distinction affects onset speed and drug clearance but may also underlay observations that fentanyl overdoses may require additional naloxone doses to prevent “renarcotization”. Other reports have suggested that fentanyl users may require higher buprenorphine doses to stabilize patients, and more severe and prolonged Neonatal Abstinence Syndrome (NAS) may occur when fentanyl is involved. The generalizability of these observations is not yet clear. Research is urgently needed to understand the nature, extent, clinical manifestations, and treatment of fentanyl addiction and overdose.

Research Objectives

In order to rapidly improve our understanding of the nature, extent, clinical manifestations and treatment of fentanyl addiction and overdose, NIDA is encouraging the submission of applications of Administrative Supplements to active grants on, although not limited to, the following research areas of interest:

  • To identify the prevalence and incidence of fentanyl addiction and overdose in the general and special populations.
  • To examine the risk and protective factors for fentanyl addiction and overdose.
  • To evaluate the clinical characteristics of fentanyl addiction and overdose and contrast them with those associated with the use of other opioids, particularly among pregnant and postpartum women.
  • To study the clinical outcomes of fentanyl addiction and overdose treatments and contrast the outcomes of approved treatments in patients with other opioid use disorders.
  • To determine the safety and efficacy of pharmacological interventions to reverse fentanyl overdose. For example, should naloxone doses be higher? Are long-acting formulations of naloxone needed? Are there other medications or medication combinations that would be more effective ?
  • To evaluate opioid detoxification strategies for patients addicted to fentanyl.
  • To study the transition from fentanyl addiction to medications to treat opioid use disorder, including opioid agonist, partial agonist, and antagonist treatments.
  • To evaluate the outcomes of relapse prevention in patients formerly addicted to fentanyl.
  • To identify the challenges associated with reversing fentanyl-induced respiratory depression.
  • To compare the pharmacology and toxicology of fentanyl versus other opioids. For example, examine whether equivalent doses of morphinan-opioids and fentanyl analogs exert differential effects on respiration. This may include effects on central and peripheral respiratory rhythm control, differential effects on thoracic musculature and alveolar gas transfer.
  • To evaluate the effects of fetal exposure to fentanyl and the incidence and clinical manifestations of Neonatal Abstinence Syndrome.
  • To evaluate the safety and efficacy of pharmacological treatments in pregnant and postpartum women addicted to fentanyl.
  • To study the safety and efficacy of pharmacological and non-pharmacological interventions for neonates exposed in-utero to fentanyl and derivatives.
  • To evaluate the cost-benefit of interventions for fentanyl exposed mothers and their infants. For example, can interventions shorten hospital stays for fentanyl exposed neonates?
  • To evaluate drug-drug interactions of fentanyl with other drugs of abuse such as cocaine and methamphetamine.
  • To study drug-drug interactions of fentanyl with medications to treat opioid use disorders such as methadone and buprenorphine.
  • To eetermine drug-drug interactions of fentanyl with medications to treat HIV and SARS-CoV-2 infection.
  • To understand the respiratory effects of SARS-CoV-2 infection among individuals with fentanyl addiction or overdose.
  • To evaluate the impact of fentanyl overdoses on health services, in particular emergency departments.
  • To evaluate the impact of fentanyl addiction and overdose on the society at large, for example schools, homeless people, family dynamics, etc.

Investigators planning to submit an application in response to the NOSI are strongly encouraged to contact the program officers listed below to discuss the proposed project in the context of the parent award.

Application and Submission Information

The parent NIDA award must be active when the supplement application is submitted (e.g., within the originally reviewed and approved project period), regardless of the time remaining on the current project. Administrative Supplements are intended to provide funds for NIH grantees where the work proposed in the supplement is fully within the scope of the ongoing grant.

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.

  • PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

  • Applications will be accepted anytime through March 31, 2022 by 5:00 PM local time of the applicant organization. This NOSI expires on April 1, 2022.
  • IMPORTANT: For funding consideration, all applicants must designate“NOT-DA-21-032” (without quotation marks) in the Agency Routing Identifier field (Box 4b) of the SF424 (R&R) Form. Applications without this information in Box 4b will not be considered for this initiative.
  • Only electronic submissions will be accepted for this funding opportunity. Use one of the methods described in PA-20-272. Paper submissions and applications submitted as email attachments will be rejected without review. All applications (including those for multi-project activity codes) must be submitted electronically using a single-project application form package.
  • Application budgets are generally limited to no more than $100,000 direct costs per year. Should the proposed research require a higher budget, the applicant should consult with the program official assigned to the parent award and include a strong justification for the larger budget in the supplement application. The proposed budget must reflect the actual needs of the proposed project.
  • The award project period of the submission should not exceed two years or the end date of the parent award (whichever is soonest).
  • The Research Strategy section of the application is limited to 6 pages

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.


Please direct all inquiries to:

Aidan Hampson, Ph.D.
National Institute on Drug Abuse
Telephone: 301-827-5925

Ivan Montoya, M.D.,M.P.H.
National Institute on Drug Abuse
Telephone: 301-827-5936

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