Warrior CARE: Cannabis Behavioral Health

Phase 1

Not yet recruiting

• Conditions: Post Traumatic Stress Disorder; Cannabis Use; Suicide; Veterans; Marijuana
• Interventions: Drug: Tetrahydrocannabinol; Drug: Cannabidiol; Drug: Placebo

• Registration Number: NCT06381180
• Lead Sponsor: Wayne State University

Brief Summary

This study is a randomized, controlled clinical trial to examine the therapeutic potential of cannabinoids for treating veterans with PTSD and suicidal ideation.

Detailed Description

In this clinical trial, we will recruit veterans with PTSD who report using cannabis or have interest in trying cannabis for symptom relief. Veterans will be randomized into one of four different groups: THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), THC+CBD, and Placebo, and undergo a 12-week treatment phase where they will be asked to smoke their assigned cannabis dose every day for 12 weeks. Participants will complete weekly questionnaires regarding their mood, behavior and drug consumption. Furthermore, there is a laboratory component that will assess cognition, fear conditioning, and other PTSD-related measures.

Study Timeline

• Study First Submitted: 2023-01-17
• Study First Submitted QC: 2024-04-18
• Study First Posted: 2024-04-24
• Status Verified: 2025-09
• Study Start: 2025-09-22
• Last Update Submitted: 2025-09-23
• Last Update Posted: 2025-09-29
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• a healthy veteran who has served in a branch of the US armed forces
• report using cannabis within the past year
• currently meet DSM-5 criteria for PTSD and a score of 25 or greater on the CAPS-5 (the anchor, or index, trauma does not have to be related to military service)
• between the ages of 19-69 years old
• not seeking treatment for Cannabis Use Disorder
• stable (i.e., under the care of a physician or therapist and not experiencing acute symptoms) on psychotropic medications and/or psychotherapy before the study begins (participants can be in treatment for PTSD)
• agree to adhere to study procedures

Exclusion Criteria

• pregnant, lactating, or heterosexually active women and not using medically approved birth control
• current or past bipolar or psychotic disorder as determined using the SCID-5
• at immediate high risk for suicide based on the C-SSRS
• current SUD other than Nicotine Use Disorder and Alcohol Use Disorder (mild or moderate)
• allergies and/or other contradictions for using cannabis
• any clinically significant medical problems
• systolic/diastolic BP >140/90 mmHg or systolic BP <95 mmHg
• elevated liver function tests
• exhibit cognitive impairment (<80 IQ)
• enrolled in another clinical trial or have received any drug as part of a research study within 30 days of dosing
• used a prescription medication (with the exception of birth control) within 14 days of study entry that in the opinion of the medically responsible investigator will interfere with the safety of the participant or the study results
• unable to provide informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
THC Group	Tetrahydrocannabinol	Cannabis with 5 mg THC; up to a maximum of 5 doses/day (max dose = 25 mg THC)
CBD Group	Cannabidiol	Cannabis with 5 mg CBD; up to a maximum of 5 doses/day (max dose = 25 mg CBD)
THC & CBD Group	Tetrahydrocannabinol	Cannabis with 5 mg THC and 5 mg CBD; up to a maximum of 5 doses/day (max doses = 25 mg THC and 25 mg CBD)
THC & CBD Group	Cannabidiol	Cannabis with 5 mg THC and 5 mg CBD; up to a maximum of 5 doses/day (max doses = 25 mg THC and 25 mg CBD)
Placebo Group	Placebo	Cannabis with \<1mg THC and \<1mg CBD; up to a maximum of 5 doses/day (max dose = \<5 mg THC and \<5 mg CBD)

Primary Outcome Measures

Name	Time	Method
Assessing change in PTSD diagnosis and its symptom severity from pre-treatment to post-treatment using the CAPS-5 assessment.	Administered at a pre-treatment visit (at the initial screening visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	PTSD diagnosis will be assessed using the Clinician-Administered PTSD Scale (CAPS-5) for DSM-5 Total Severity Score, a well-validated, semi-structured clinician interview that determines the presence and severity of PTSD symptoms and diagnosis consistent with the DSM-5 and allows for assessing changes in symptom severity over time.
Assessing change in PTSD diagnosis and its symptom severity throughout the study using the PCL-5 assessment	Administered at every study visit: both pre-treatment visits (the initial screening and baseline visit); during the 12-week treatment phase (all twelve weekly visits); and the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months	The PCL-5 is a 20-item self-report measure that assesses DSM-5 symptoms of PTSD. The PCL-5 is used to monitor symptom change during and after treatment, screen individuals for PTSD, and make a provisional PTSD diagnosis. This assessment will also be used as a safety measure at all visits by assessing PTSD symptom severity.
Assessing Suicidality over time using the C-SSRS assessment.	Administered at a pre-treatment visit (at the initial screening visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	The Columbia Suicide Severity Rating Scale (C-SSRS) is a clinician-administered interview assessing suicidal thoughts and behaviors over time. A baseline form is used to assess lifetime suicidal ideation, intensity, and behavior, and can be compared to current suicidal ideation and intensity assessed over the clinical trial.
Assessing Suicidality throughout the study using the SBQ-R assessment.	Administered at every study visit: both pre-treatment visits (the initial screening and baseline visit); during the 12-week treatment phase (all twelve weekly visits); and the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months	The Suicide Behavior Questionnaire-Revised (SBQ-R) is a brief (4-item), self-administered questionnaire that taps into four dimensions of suicidality (lifetime ideation/attempt, frequency of recent ideation, risk of suicide attempt and self-reported likelihood of future suicidal behavior). This assessment will also be used as a safety measure at all visits by assessing suicidality.
Assessing mood and anxiety symptoms throughout the study using the BDI-II and STAI-Y Questionnaires.	Administered at every study visit: both pre-treatment visits (the initial screening and baseline visit); during the 12-week treatment phase (all twelve weekly visits); and the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months	The Beck Depression Inventory-II (BDI-II) is a self-report depression checklist which assesses neurovegetative depressive symptoms. One item asks specifically about suicidal thoughts and will also be checked at every study visit as a safety measure. The State Trait Anxiety Inventory-Form Y (STAI-Y) is a 40-item questionnaire with two scales assessing state and trait anxiety (somatic and cognitive symptoms).

Secondary Outcome Measures

Name	Time	Method
Assess emotional state pre- and post-treatment using the PANAS questionnaire.	Administered at a pre-treatment visit (at the baseline visit); and at the first post-treatment visit (one week post-treatment).	The Positive and Negative Affect Schedule (PANAS) is a 20-item self-report questionnaire, widely used measure of emotional state, which has excellent psychometric properties.
Assess dissociative symptoms pre- and post-treatment using the MDI and DSS assessments.	Administered at a pre-treatment visit (at the baseline visit); and at the four post-treatment visits (one week post-treatment, and 3-, 6-, and 9-months post-treatment).	The Multiscale Dissociation Inventory (MDI) is a self-report questionnaire of dissociative symptomatology over the past month. The Dissociation Tension Scale (DSS) is a self-report measure of dissociative symptoms sensitive to weekly changes.
Assess smoking habits and history using the FTND assessment	Administered once at a pre-treatment visit, specifically at the baseline visit.	Subjects who smoke cigarettes will also complete the Fagerstrom Test for Nicotine Dependence (FTND) survey to assess smoking history and habits.
Assess feelings of loneliness pre- and post-treatment using UCLA's 3-ILS assessment.	Administered at a pre-treatment visit (at the initial screening visit); and at the first post-treatment visit (one week post-treatment).	The UCLA Three-Item Loneliness Scale (3-ILS) assesses social isolation and feelings of loneliness.
Assess drug effects, liking, and symptoms after cannabis administration using the SCERF and SES visual analog scales.	Administered after cannabis administration; therefore, administered at the baseline visit and electronically during the 12-week treatment phase (at all twelve weekly visits).	The Subjective Cannabis Effects Rating Form (SCERF) will ask participants to complete a Visual Analog Scale (VAS) of "good drug effect," "bad drug effect," "strength of drug effect," liking," "sedated," and "desire to take again" and indicate whether they thought they received active drug or placebo. The Subjective Effects Scale (SES) VAS is a 33-item scale which includes the phrase "I feel…" followed by adjectives describing a mood (e.g., "anxious", "friendly," "down," etc.), a drug effect (e.g., "high," "stimulated", "a good drug effect") or a physical symptom (e.g., "hungry," "tired," "restless").
Assess overall quality of life pre- and post-treatment using the QOL questionnaire.	Administered at a pre-treatment visit (the baseline visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	The Quality of Life (QOL) inventory assesses satisfaction in 17 life areas (work, health, recreation, goals, etc.) and will be used to assess the quality of life changes.
Assess biological samples for genetic markers associated with the endocannabinoid system and other biomarkers (e.g., cortisol) and measure THC and CBD.	Biological samples may be collected at a pre-treatment (at the baseline visit); during the 12-week treatment phase; and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits)	Biological measures include collection of urine, saliva, and blood. Saliva will be used to measure biomarkers like cortisol and test for endocannabinoid levels. Urine will be used to measure THC and CBD and their metabolites. Blood plasma will be used to measure plasma concentrations of endocannabinoids, cannabinoids, and PUFA metabolites.
Assess demographics using a self-report assessment	Administered once at a pre-treatment visit, specifically at the initial screening visit.	Participants will be asked to complete a personal history form to assess age, gender, sex, gender identity, marital status, race/ethnicity, education, employment status, and annual income.
Assess toxicant exposure commonly experienced during war using the KGWIC and BPE assessments.	Administered once at a pre-treatment visit, specifically at the baseline visit.	The Kansas Gulf War Illness Criteria (KGWIC) and the Burn Pit Exposure (BPE) are self-report questionnaires that contain items on toxicants commonly experienced as well as burn pit exposure during war.
Assess sleepiness pre- and post-treatment using the ESS questionnaire.	Administered at a pre-treatment visit (the baseline visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	The Epworth Sleepiness Scale (ESS) is a self-report questionnaire that will be used to assess daytime sleepiness, which is indicative of sleep problems.
Assess general health and history pre- and post-treatment using the SF-36 assessment.	Administered at a pre-treatment visit (the baseline visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	The Short Form 36 (SF-36) is a brief measure of overall self-reported health that is associated with other objective health measures. Scores will be examined to assess change in general health outcomes over time.
Assess pain pre- and post-treatment using the BPI assessment.	Administered at a pre-treatment visit (the baseline visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	The Brief Pain Inventory (BPI) asks participants to identify areas on their body causing pain and rate the severity.
Assess substance use throughout the study using the TLFB assessment.	Administered at every study visit: both pre-treatment visits (the initial screening and baseline visit); during the 12-week treatment phase (all twelve weekly visits); and the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months	The Timeline Follow-Back (TLFB) will be used to record the time of cannabis use and route of administration as well as any alcohol and other drug use.
Assess healthcare utilization throughout the study.	Administered at both pre-treatment visits (the initial screening and baseline visit); and at two post-treatment visits (one week post-treatment and 3-months post-treatment visits).	The Healthcare Utilization (HU) survey will also assess the number of times participants utilize emergency room, urgent care, specialist, and general practitioner services.
Assess neurocognitive and executive function pre- and post-treatment using the WCST, WMS, CVLT, HMDD, WCS, IGT tasks	Administered at a pre-treatment visit (the baseline visit); and at the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months post-treatment visits).	Working Memory will be assessed using the Wechsler Memory Scale (WMS) and the California Verbal Learning Test (CVLT). The Wisconsin Card Sort Task (WCST) assesses abstraction and the ability to shift or maintain cognitive set. The Hypothetical Monetary Delay Discounting (HMDD) and the Iowa Gambling Task (IGT) measure decision-making. Lastly, the Word Color Stroop (WCS) task assesses selective attention capacity and skills.
Assess physiological measures throughout the study as a safety check	Administered at every study visit: both pre-treatment visits (the initial screening and baseline visit); during the 12-week treatment phase (all twelve weekly visits); and the four post-treatment visits (one week post-treatment and 3-, 6-, and 9-months	Physiological measures include blood pressure, heart rate, oxygen saturation, and skin temperature checks at all study visits

Trial Locations

Locations (1)

Wayne State University; 🇺🇸 Detroit, Michigan, United States