Clinical trial NCT06222268: Wayne State Warriors Marijuana Clinical Research Program: Cannabinoid Adjunct to Prolonged Exposure & Recovery
Official title: Wayne State Warriors Marijuana Clinical Research Program: Cannabinoid Adjunct to Prolonged Exposure & Recovery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: PTSD
Post Traumatic Stress Disorder
Keywords: Veterans
Lead sponsor: Wayne State University
Sponsor class: OTHER
First posted: 2024-01-24
Enrollment: 350
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 overall strategy is to recruit veterans with PTSD who report minimal current cannabis use but are interested in or considering therapeutic cannabis to manage mental health symptoms (anxiety, depression, PTSD and/or suicidality). The information gained from this study could lead to the development of new treatments for persons who suffer from post-traumatic stress disorder and maintain better mental health.

Detailed description: The total time commitment estimated per participant 21 study visits. This is broken down below:

Visit 1: Pre-Screening and informed Consent: During this visit the potential participant will learn about the study procedures and sign the informed consent documents. Also, during this visit a licensed clinician will administer the (CAPS-5).

Visit 2: Physical Examination and Questionnaires: During this visit the participant will undergo a full physical examination conducted by a licensed medical professional. At this time, they will collect blood, urine, breathalyzer and saliva samples.

Visit 3: Pre-Treatment Behavioral Tasks and Neurocognitive Assessments: During this visit, we will administer behavioral tasks that measure reward decision-making.

Visit 4 Pre-Treatment Fear Acquisition \& Extinction Learning 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 5: Pre-Treatment Fear Extinction Recall with MR Scan: This visit will be very similar to Visit 4. 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 4. 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 6\&7: 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 the Subjective Units of Distress Scale (SUDS) to assess level of distress from 0 to 100 (100=extreme anxiety/distress) when facing fears. One session occurs weekly across 2 weeks.

Visit 8-11: 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 3-6) either cannabis or placebo (PBO) will be administered just before the session. One session occurs weekly across 8 weeks.

Visit 12: This visit is similar as the previous just a little longer due to a mid-treatment assessment. (Session 7)

Visit 13-15: 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 8-10) either cannabis or PBO will be administered just before the session. One session occurs weekly across 8 weeks.

Visit 16: Post-Treatment Assessments: PE Session 11 will include a review of therapeutic gains/relapse prevention/assessments.

Visit 17: Post-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 4. 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 4. 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: Post- Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 5. 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 5. 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 19: 3-Month Follow-Up Treatment Assessment: This session is similar to Visit 16 and will include review of therapeutic gains/relapse prevention/assessments.

Visit 20: 6-Month Follow-Up Treatment Assessment: This session is similar to Visit 19 and will include review of therapeutic gains/relapse prevention/assessments.

Visit 21: 9-Month Follow-Up Treatment Assessment: This session is similar to Visit 20 and will include review of therapeutic gains/relapse prevention/assessments.

Eligibility criteria: Inclusion Criteria:

* Willing and able to consent to the study
* Agree to comply with requirements and procedures
* Veteran who has served in a branch of the US armed forces
* Between ages 18-60
* Report using cannabis at least once, or using cannabis no more than once a week within the past 3 months and fewer than 100 times lifetime
* Exposure to Criterion A stressor defined by CAPS-5 and identified by Life Events Checklist-5 (LEC-5); trauma does not have to be related to combat or military service
* 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
* not currently receiving any psychotherapy for PTSD

Exclusion Criteria:

* Pregnant, nursing or trying to get pregnant.
* Current or past diagnosis of bipolar, schizophrenia spectrum, psychotic and related disorders
* Risk of harm to self or others that requires immediate intervention
* Current severe alcohol use or any substance use other than cannabis or nicotine
* Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to smoking or vaporizing cannabis
* Concomitant treatment with medication taken daily that has level 1 evidence indicating severe drug-drug interactions with cannabis
* Current diagnosis with hematological, endocrine, cerebrovascular, cardiovascular, systemic pulmonary, immunocompromising, or neurological disease
* Currently receiving psychotherapy for PTSD or previously received exposure-based PTSD treatment
* Current diagnosis of a mood, anxiety, or other disorder that is more clinically salient than PTSD
* Lack of fluency in English
* Pervasive development disorder history
* Traumatic brain injury (TBI) with current cognitive impairment related to TBI
* Exclusively left-handed (score of -100 on Handedness Questionnaire)
* claustrophobic
* MRI contraindications (e.g., ferrous metal in head/body)

Primary outcomes:
measure: Treatment Response
timeFrame: Through study completion, an average of 9 months
Secondary outcomes:
measure: Brain measures
timeFrame: Pre and post treatment-Through study completion, an average of 9 months
measure: Heart rate
timeFrame: through study completion, an average of 9 months
measure: Blood pressure
timeFrame: through study completion, an average of 9 months
measure: Skin conductance response
timeFrame: through study completion, an average of 9 months
measure: Drug Effects Questionnaire (DEQ)
timeFrame: through study completion, an average of 9 months
measure: Visual Analogue Scale of Mood (VAS)
timeFrame: through study completion, an average of 9 months
measure: Quality of Life Inventory (QOLI)
timeFrame: through study completion, an average of 9 months
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: through study completion, an average of 9 months
measure: Epworth Sleepiness Scale (ESS)
timeFrame: through study completion, an average of 9 months
measure: Brief Pain Inventory (BPI)
timeFrame: through study completion, an average of 9 months
measure: Short form 36
timeFrame: through study completion, an average of 9 months
measure: fMRI
timeFrame: through study completion, an average of 9 months
measure: Psychophysiology
timeFrame: through study completion, an average of 9 months
measure: DNA analysis
timeFrame: through study completion, an average of 9 months
measure: Cannabinoid concentration - Blood
timeFrame: through study completion, an average of 9 months
measure: Drug/Pregnancy tests
timeFrame: through study completion, an average of 9 months
measure: Cannabinoid concentration - Salvia
timeFrame: through study completion, an average of 9 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Tolan Park Medical Building
state: Michigan
city: Detroit
country: United States
facility: Wayne State University Eugene Applebaum College of Pharmacy & Health Sciences
state: Michigan
city: Detroit
country: United States
facility: WSU MR Research Facility DMC Harper University Hospital
state: Michigan
Study officials:
References: