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

Not Applicable

Completed

Conditions: Post-Traumatic Stress Disorder

Interventions: Drug: Placebo
Drug: Dronabinol

Registration Number: NCT02069366

Lead Sponsor: Wayne State University

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.

Detailed Description: The total time that for each participant involved in this study is 4 visits, as outlined below:

Visit 1: Questionnaires, Screening, and Orientation: During this visit the potential participant will learn about the study procedures, sign the informed consent documents, and fill out a packet of forms that ask about his or her race and ethnic background, use of drugs and alcohol and physical and mental health.

Visit 2: Behavioral Tests: During this visit the participant will complete several computer tasks, and the study staff will be measuring reaction time and psychophysiological measures.The tasks that the participant will perform will show three different images and an aversive stimulus (e.g. loud burst of noise or mild wrist shock) may follow one image most of the time, while the other images may never be followed by a noise or mild wrist shock. The participant will need to try to predict whether the aversive cue will occur or not based on which image is shown and will be asked to repeatedly rate on a scale how likely it is that he or she thinks a noise/shock will occur after each image. Lastly, during the session the participant will also be asked to report his or her level of anxiety on a scale from 0 to 100.

Visit 3: Behavioral Tests with Drug or Placebo and MRI scan: For safety reasons participant will not be allowed to take any drugs for at least 24 hours before this visit, and should not use marijuana for at least 2 weeks before. Participants will be required to pass a urine drug test (and pregnancy test for women) and breathalyzer test before being allowed to continue with this visit. The participant will also not be allowed to drive himself or herself home from this visit, so he or she should arrange a friend or family member to pick him or her up or a taxi can be called by our research staff.

The participant will view the same images he or she did on the previous day (Visit 2), and may experience the same aversive stimulus as during Visit 2. The participant will again be asked to rate how much he or she expects to experience the aversive stimulus after each image and he or she will also be asked to report his or her level of anxiety on a scale from 0 to 100. However, about 2 hours before the task begins, the participant will be asked to swallow a capsule containing either a marijuana-like drug (Dronabinol) or a placebo (sugar pill). Dronabinol is a Food \& Drug Administration (FDA) approved drug and the dose (7.5mg; one time) is unlikely to have any effects that last beyond the duration of the study visit. About every 30 minutes after taking the pill, the participant will fill out some questionnaires about mood and how he or she is feeling at the moment.

Visit 4: Behavioral Tests and MRI scan: This visit will be very similar to Visit 2. Participants will participate in the same type of task inside the MRI scanner, while the study staff measures reaction time and psychophysiological responding and brain activation. Participants will view the same images he or she did previously, and may experience the same aversive stimulus as during Visit 2. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and will also be asked to report their level of anxiety on a scale from 0 to 100.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 86

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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)
Dronabinol	Dronabinol	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)

Primary Outcome Measures

Name	Time	Method
Expectancy Ratings	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.	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.
Brain Measures	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	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.

Secondary Outcome Measures

Name	Time	Method
Subjective Units of Distress (SUDS)	SUDS ratings are collected at Visit 3, 14 days from baseline (Visit 1), and Visit 4, 15 days from baseline (Visit 1), at 3 timepoints within each visit: before the task begins (Pre), in the middle of the task (Mid), and at the end of the task (Post).	Subjective Units of Distress (SUDS): used to measure fear ratings/"subjective" anxiety on a scale from 0-10; taken at three time points throughout the tasks: before the task begins, in the middle of the task, and at the end of the task. A rating of "0" means no anxiety and a ratings of "10" means worst anxiety ever experienced.