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

NCT ID: NCT02069366

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2019-12-31

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.

Conditions

Post-Traumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

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)

Group Type: ACTIVE_COMPARATOR

Dronabinol

Intervention Type: 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.

Interventions

Dronabinol

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Marinol; sugar pill

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)
• Life history of bipolar disorder, schizophrenia, or presence of an organic mental syndrome, mental retardation, or pervasive developmental disorder
• Current or in the past 6 months alcohol/drug abuse of dependence
• Current or in the past 6 months major depressive disorder
• Current suicidal ideation
• Diagnosis of an Axis II personality disorder
• Concomitant treatments with psychotropic/psychoactive medication [including beta-adrenergic blockers, selective serotonin reuptake inhibitor (SSRI), benzodiazepines, tricyclic or monoamine oxidase inhibitor (MAOI) antidepressants, lithium, antiepileptic/anticonvulsants, neuroleptics/antipsychotics, etc.) or in the past two weeks [8 weeks for fluoxetine and 4 weeks for MAOIs) before screening (Visit 1)
• currently receiving exposure-based therapy for PTSD

• Current or past Axis I psychiatric disorder [including alcohol/substance abuse of dependence disorder]

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Christine Rabinak, PhD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christine A. Rabinak, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

Eugene Applebaum College of Pharmacy and Health Sciences

Detroit, Michigan, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38767196 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35141873 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1K01MH101123-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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