Clinical trial NCT04080427: Effects of Delta9-tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study
Official title: Effects of THC on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Posttraumatic Stress Disorder
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2019-09-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Detailed description: The total time commitment estimated per participant 18 study visits. This is broken down 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: Pre-Treatment Behavioral Tests and and Magnetic Resonance (MR) Scan: 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 animated snake) may follow one image most of the time, while the other images may never be followed by the aversive cue. 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 an aversive cue 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: Pre-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 2. Participants will participate in the same type of task inside the MR 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.

Visits 4 \& 5: Prolonged Exposure (PE) Sessions 1 \& 2: These sessions will consist of psychoeducation that includes discussion or reactions to trauma , treatment rationale, breathing retraining, and review of SUDS to assess level of distress from 0 to 100 (100=extreme anxiety/distress) when facing fears. One session occurs weekly across 2 weeks.

Visits 6-14: PE Sessions 3-11: These sessions will consist of repeated exposures to trauma memories (imaginal exposure) and avoided situations (in vivo exposure). As is standard, patients will also practice exposures (e.g., listen to tapes of imaginal exposure, carry out in vivo exposure) outside of PE sessions as "homework". At exposure-focused sessions (Sessions 3-11) either THC or PBO will be administered just before the session. One session occurs weekly across 8 weeks.

Visit 15: PE Session 12 \[Post-treatment Assessment\]: This session will include a review of therapeutic gains/relapse prevention/assessments.

Visit 16: Post-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 2. Participants will participate in the same type of task inside the MR 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.

Visit 17: Post-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 3. Participants will participate in the same type of task inside the MR 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 3. 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.

Visit 18: 3-Month Follow-Up Treatment Assessment: This session is similar to Visit 15 and will include review of therapeutic gains/relapse prevention/assessments.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Brain Measures
timeFrame: Through study completion, an average of 3 months.
measure: Psychophysiology
timeFrame: Through study completion, an average of 3 months.
measure: Expectancy Ratings
timeFrame: Through study completion, an average of 3 months.
measure: PTSD Checklist (PCL-5)
timeFrame: Through study completion, an average of 3 months.
measure: Clinician Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5)
timeFrame: Through study completion, an average of 3 months.
measure: Subjective Units of Distress Scale (SUDS)
timeFrame: Through study completion, an average of 3 months.
Secondary outcomes:
measure: Visual Analogue Scale of Mood (VAS)
timeFrame: Through study completion, an average of 3 months.
measure: Drug Effects Questionnaire (DEQ)
timeFrame: Through study completion, an average of 3 months.
measure: Addiction Research Center Inventory (ARCI)
timeFrame: Through study completion, an average of 3 months.
measure: State-Trait Anxiety Inventory (STAI)
timeFrame: Through study completion, an average of 3 months.
measure: End of Session Questionnaire (ESQ)
timeFrame: Through study completion, an average of 3 months.
measure: Heart Rate
timeFrame: Through study completion, an average of 3 months.
measure: Blood Pressure
timeFrame: Through study completion, an average of 3 months.
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Eugene Applebaum College of Pharmacy and Health Sciences
state: Michigan
Study officials:
affiliation: Wayne State University
name: Christine A Rabinak, PhD
role: PRINCIPAL_INVESTIGATOR
References: