Notice of Special Interest: NIMH’s Interest in Early Stage Clinical and/or Mechanistic Trials in Posttraumatic Psychopathology, Directed at Testing FAAH Inhibitors

Notice Number: NOT-MH-19-055

Key Dates
Release Date: October 17, 2019
First Available Due Date: February 05, 2020
Expiration Date: January 08, 2022

Related Announcements

NOT-MH-19-031, Consolidated Notice on NIMH Clinical Trials Policies

PAR-18-427, First in Human and Early Stage Clinical Trials of Investigational Drugs or Devices for Psychiatric Disorders (U01 Clinical Trial Required)

RFA-MH-18-702, Early Stage Testing of Pharmacologic or Device-based Interventions for the Treatment of Mental Disorders (R61/R33 Clinical Trial Required)

PA-19-092, NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PA-19-091, NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

Issued by
National Institute of Mental Health (NIMH)

Purpose

NIMH is issuing this Notice of Special Interest (NOSI) to highlight its interest in supporting early stage intervention development   and/or Basic Experimental Studies with Humans to investigate fatty acid amide hydrolase (FAAH) inhibitors in posttraumatic psychopathology.

FAAH inhibition was selected based on the hypothesis that the endocannabinoid system is relevant to the onset, course, and potentially treatment of neuropsychiatric disorders, including those that occur following trauma exposure. This would potentially include how the brain adapts to and extinguishes fear and how the dynamic functions of memory acquisition, consolidation, and extinction are influenced by neurodevelopment, aging, and other factors in at risk or symptomatic individuals.

FAAH inhibitors may have advantages over cannabinoid receptor agonists. For example, increasing the concentration of endocannabinoids rather than manipulation through agonists might minimize adverse events e.g., impairments in cognitive, motor, and psychotic domains. Further FAAH inhibitors are a class of drugs for which there is adequate animal and human data publicly available to consider in designing trials, including relevant safety profiles which vary by compound.

Specifically, the NIMH is interested in supporting early stage testing of FAAH inhibitors using a protocol design where the presumed mechanism(s) of action is adequately tested, to provide meaningful information where target modulation yields a dose-dependent neurophysiological/clinical/behavioral effect. This interest is not limited to treatment of illness once it has manifest, but also intervention on specific processes in an acute phase post trauma exposure that may disrupt the development of illness following trauma. Beyond use in intervention development, research using FAAH inhibitors to generate information about the mechanisms underlying illness by measuring responses to the experimental manipulation is also of interest. Specifically, the effects of FAAH inhibition on circuits and systems to understand relevant aspects of posttraumatic psychopathology is highly relevant and encouraged.

Examples of questions to be addressed might include, but are not limited to, the effects of FAAH inhibition on:

  • recall of fear extinction learning
  • expression of arousal
  • mitigation of pain
  • sleep fragmentation, nightmares and general sleep architecture
  • brain function and changes in eCB signaling – to map stability or change in function to risk, development, and sustainment of illness

Research applications that are incremental or redundant with ongoing or prior work are not considered a priority (see clinicaltrials.gov and NIH RePORTER for current and prior studies).

Investigators interested in the research specified by this NOSI should apply through the active intervention development or Basic Experimental Studies with Humans Funding Opportunity Announcements (FOAs).    

NIMH strongly advises interested applicants to contact the Scientific/Research program contacts listed below prior to submission to discuss:

  • interest in supporting the proposed research project,
  • availability and access to compounds, and
  • the most appropriate funding mechanism

This NOSI does not supersede guidance provided in NOT-MH-19-031.

The NIMH requires expertise as outlined in the above FOAs focused on the design and conduct of trials using Investigational New Drugs. Attention and consideration must be given to protocol sensitivity to prior adverse events with FAAH inhibitors. Additionally, the site(s) which are proposed to conduct the studies are required to have regulatory infrastructure expertise to conduct drug trials.

Application and Submission Information

This notice applies to due dates on or after January 5, 2020 and subsequent receipt dates through January 8, 2022.

Submit applications for this initiative using one of the following FOAs or any reissues of these announcements through the expiration date of this notice.

  • PA-19-091– NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
  • PA-19-092– NIH Research Project Grant (Parent R21 Basic Experimental Studies with Humans Required)
  • PAR-18-427-First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Devices for Psychiatric Disorders (U01 Clinical Trial Required)
  • RFA-MH-18-702– Early Stage Testing of Pharmacologic or Device-based Interventions for the Treatment of Mental Disorders (R61/R33- Clinical Trial Required)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

For funding consideration, applicants must include “NOT-MH-19-055” (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.

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

 

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Susan Borja, Ph.D.
National Institute of Mental Health
Telephone: 301-443-1252
Email: susan.borja@nih.gov

Farris Tuma, Sc.D.
National Institute of Mental Health
Telephone: 301-443-9232
Email: ftuma@nih.gov