Cannabinoid Control of Fear Extinction Neural Circuits in Post-traumatic Stress Disorder

NCT02069366 | Completed Results DMC

• 1 other identifier: 1K01MH101123-01A1
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to look at how a type of drug called cannabinoids are related to the processing of fear signals, the experience of emotions and fear, and the pattern of activity in the brain that is involved in these processes and how this relates to the development of post-traumatic stress disorder (PTSD). PTSD is an anxiety disorder that occurs after experiencing a traumatic event(s) and is characterized by unwanted memories of the trauma(s) through flashbacks or nightmares, avoidance of situations that remind the person of the event, difficulty experiencing emotions, loss of interest in activities the person used to enjoy, and increased arousal, such as difficulty falling asleep or staying asleep, anger and hypervigilance. The information gained from this study could lead to the development of new treatments for persons who suffer from anxiety or fear-based disorders.

Conditions

Post-Traumatic Stress Disorder

Keywords

Post-Traumatic Stress Disorders; Dronabinol; Extinction; fMRI

Outcome Measures

Primary Outcomes (2)

• Brain Measures

  Mean functional magnetic resonance imaging (fMRI) BOLD activation extracted from each region of interests \[amygdala; ventromedial prefrontal cortex; hippocampus\] for each stimulus type (CS+E, CS+U, CS-). The units of BOLD values are expressed as arbitrary units.

  Brain measures are collected on Visit 3, 14 days from baseline (Visit 1) and Visit 4, 15 days from baseline (Visit 1), for approximately 1.5 hours each day

• Expectancy Ratings

  To assess the expected likelihood that an aversive cue (e.g. noise burst) will occur or not based on the CS shown on the screen. Participants rate their expectancy of the aversive cue using a button box on a scale from 1 to 3 \[1 = certain that the aversive cue will be presented (Yes); 2 = certain that the aversive cue will not be presented (No); 3 = uncertain whether the aversive cue will be presented (I don't know)\]. Counts of "yes", "no", and "I don't know" are collected on the first (early) trial of the CS and the last (late) trial of the CS.

  Collected on Visit 2, 13 days from baseline (Visit 1), Visit 3, 14 days from baseline (Visit 1), and Visit 4, 15 days from baseline, during the task. Each day the task lasted approximately 20 minutes.

Secondary Outcomes (1)

• Subjective Units of Distress (SUDS)

  SUDS ratings are collected at Visit 3 (Day 14 from baseline) and Visit 4 (Day 15 from baseline), at three timepoints per visit: before the task (Pre), midpoint (Mid), and after the task (Post), each averaged over ~1 minute.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

In a randomized, double-blind, placebo-controlled, between-subjects design, we will administer a one-time oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to fMRI scanning and task performance in 40 patients with PTSD, 40 trauma-exposed controls without PTSD (TEC), and 40 non-exposed healthy controls (HC). Within each of the three groups half of the participants will receive dronabinol and the other half will received placebo to create the following 6 groups: 1. PTSD-dronabinol (20) 2. PTSD-placebo (20) 3. TEC-dronabinol (20) 4. TEC-placebo (20) 5. HC-dronabinol (20) 6. HC-placebo (20)

Drug: Placebo

Dronabinol

ACTIVE COMPARATOR

In a randomized, double-blind, placebo-controlled, between-subjects design, we will administer a one-time oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to fMRI scanning and task performance in 40 patients with PTSD, 40 trauma-exposed controls without PTSD (TEC), and 40 non-exposed healthy controls (HC). Within each of the three groups half of the participants will receive dronabinol and the other half will received placebo to create the following 6 groups: 1. PTSD-dronabinol (20) 2. PTSD-placebo (20) 3. TEC-dronabinol (20) 4. TEC-placebo (20) 5. HC-dronabinol (20) 6. HC-placebo (20)

Drug: Dronabinol

Interventions

Dronabinol DRUG

Dronabinol (7.5mg) is administered only once (approximately 120 min prior to fMRI scanning in Visit 3) by the oral route and is placed in opaque capsules with dextrose filler. Half of the participants in each diagnostic group \[HC = 20; PTSD = 20; TEC = 20\] will receive dronabinol.

Also known as: Marinol

Dronabinol

Placebo DRUG

Placebo is administered only once (approximately 120 min prior to fMRI scanning in Visit 3) by the oral route and contains only dextrose in opaque capsules. Half of the participants in each diagnostic group \[HC = 20; PTSD = 20; TEC = 20\] will receive placebo.

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to give informed consent
• Physically and neurologically healthy \[confirmed by a comprehensive medical history\]
• Age between 21-45 years old
• Right-handed
• Current PTSD diagnosis \[related to civilian trauma\]
• Experience with a civilian trauma without a PTSD diagnosis
• Free of a lifetime Axis I or Axis II diagnosis
• Free of a lifetime Axis I or Axis II diagnosis

You may not qualify if:

• Clinically significant medical or neurological condition
• Less than a high school education
• Lack of fluency in English
• Night shift work
• Currently pregnant; planning pregnancy; or lactating
• Unwilling/unable to sign informed consent document
• Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia)
• Left-handed
• Presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
• Under 21 or over 45 years of age
• Anticipation of a required drug test in the 4 weeks following study participation
• Positive urine drug screen and/or alcohol breathalyzer
• Current or past allergic or adverse reaction or known sensitivity to cannabinoid-like substances \[dronabinol/marijuana/cannabis/thc, cannabinoid oil, sesame oil, gelatin, glycerin, and titanium dioxide\]
• Participation in an experiment involving white noise bursts or shocks in the last 6 months
• Primary comorbid anxiety disorder (defined by which disorder was the more debilitating and clinically salient)

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Eugene Applebaum College of Pharmacy and Health Sciences

Detroit, Michigan, 48201, United States

Location

Related Publications (2)

• Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.

  PMID: 38767196 DERIVED

• Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.

  PMID: 35141873 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Dronabinol; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Dr. Christine Rabinak
• Organization: Wayne State University

rabinak@wayne.edu

(313) 577-9875

Study Officials

• Christine A. Rabinak, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: February 24, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: October 2, 2025
• Results First Posted: September 9, 2022

Record last verified: 2025-09

Locations

US (1)