Effects of Delta9-tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study

NCT04080427 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: R33MH111935R61MH111935
• Study Type: interventional
• Target: 102
• 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 treatment 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

Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (6)

• Brain Measures

  functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) percent signal change within region of interests \[amygdala; ventromedial prefrontal cortex; hippocampus\]

  Through study completion, an average of 3 months.

• Psychophysiology

  Skin conductance response (SCR): change in SCR \[peak amplitude from 0.5-4.5 sec following stimulus presentation minus average 2 second baseline prior to stimulus presentation\].

  Through study completion, an average of 3 months.

• Expectancy Ratings

  To assess the change in expected likelihood that an aversive cue (e.g. noise burst or shock) will occur or not based on while slide was shown, participants will repeatedly rate their expectancy of the aversive cue using a button box on a scale from 1 to 3 \[1 = certain that the aversive cue will be presented; 2 = certain that the aversive cue will not be presented; 3 = uncertain whether the aversive cue will be presented\].

  Through study completion, an average of 3 months.

• PTSD Checklist (PCL-5)

  To track PTSD symptom change for each participant. The PCL-5 is a 20-item questionnaire. The self-report rating scale is 0-4 for each symptom: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely", respectively. A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items.

  Through study completion, an average of 3 months.

• Clinician Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5)

  To track PTSD symptom change for each participant. The CAPS is the gold standard in PTSD assessment. The CAPS is a 30-item structured interview. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype. The assessor combines information about frequency and intensity of an item into a single severity rating. Total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. The five-point CAPS-5 symptom severity rating scale is used for all symptoms (0, Absent; 1, mild; 2, Moderate/threshold; 3, Severe/markedly elevated; 4, Extreme/incapacitating). Total CAPS-5 symptom severity scores range from 0-80, with higher scores indicating worse PTSD symptom severity.

  Through study completion, an average of 3 months.

• Subjective Units of Distress Scale (SUDS)

  To assess the change in level of distress from 0 to 100 when facing fears. The higher the number on the scale the more severe the level of distress experienced.

  Through study completion, an average of 3 months.

Secondary Outcomes (7)

• Visual Analogue Scale of Mood (VAS)

  Through study completion, an average of 3 months.

• Drug Effects Questionnaire (DEQ)

  Through study completion, an average of 3 months.

• Addiction Research Center Inventory (ARCI)

  Through study completion, an average of 3 months.

• State-Trait Anxiety Inventory (STAI)

  Through study completion, an average of 3 months.

• End of Session Questionnaire (ESQ)

  Through study completion, an average of 3 months.

Study Arms (2)

Placebo capsule

PLACEBO COMPARATOR

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall. Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Drug: Placebo capsule

Dronabinol 7.5 milligram oral capsule

EXPERIMENTAL

In a randomized, double-blind, placebo-controlled, between-subjects design, the investigators will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall. Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Drug: Dronabinol 7.5 milligram oral capsule

Interventions

Placebo capsule DRUG

Placebo is administered just prior to weekly exposure sessions by the oral route and contains only dextrose in opaque capsules.

Also known as: sugar pill

Placebo capsule

Dronabinol 7.5 milligram oral capsule DRUG

Dronabinol (7.5mg) is administered just prior to weekly exposure sessions by the oral route and is placed in an opaque capsule with dextrose filler.

Also known as: Marinol

Dronabinol 7.5 milligram oral capsule

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between ages 18-60
• Willing and able to consent to study
• Generally medically and neurologically healthy (including no evidence of intellectual disability or serious cognitive impairment that would interfere with task performance)
• Exposure to Criterion A stressor defined by CAPS-5 and identified by Life Events Checklist-5 (LEC-5)
• Significant PTSD severity as indicated by CAPS-5 diagnosis and/or score \>= 25 of at least one month prior to study entry, PTSD is patient's primary concern

You may not qualify if:

• Positive urine pregnancy test prior to fMRI, self-reported current pregnancy during screening, or planning pregnancy
• Currently breastfeeding/ lactating
• MRI contraindications (e.g., ferrous metal in head/body)
• Pervasive development disorder history
• Traumatic brain injury (TBI) with current cognitive impairment related to TBI
• Risk of harm to self or others that requires immediate intervention
• Presence of contraindications, 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)
• Lack of fluency in English
• Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia
• Exclusively left-handed (score of -100 on Handedness Questionnaire)
• Current or past diagnosis of bipolar, schizophrenia spectrum, psychotic and related disorders
• Current severe alcohol or substance use
• Comorbid mood or anxiety disorder that is primary to PTSD
• Concomitant treatment with medication taken daily that has level 1 evidence indicating severe drug-drug interactions with dronabinol

Sponsors & Collaborators

• Wayne State University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Eugene Applebaum College of Pharmacy and Health Sciences

Detroit, Michigan, 48201, United States

Location

Related Publications (1)

• Rabinak CA, Kilgore PE, Lumley MA, Rauch SAM. Randomized trial of delta-9-tetrahydrocannabinol (THC) versus placebo to augment the effects of prolonged exposure therapy on fear extinction learning in post-traumatic stress disorder: Study rationale and protocol. Contemp Clin Trials. 2026 Jan;160:108148. doi: 10.1016/j.cct.2025.108148. Epub 2025 Nov 19.

  PMID: 41270825 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Sugars; Dronabinol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Carbohydrates; Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Christine A Rabinak, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor & Principal Investigator

Study Record Dates

• First Submitted: August 30, 2019
• First Posted: September 6, 2019
• Study Start: April 15, 2021
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)