Clinical trial NCT02759185: Pilot Study of the Safety and Efficacy of Four Different Potencies of Smoked Marijuana in 76 Veterans With PTSD
Official title: Placebo-Controlled, Triple-Blind, Randomized Crossover Pilot Study of the Safety and Efficacy of Four Different Potencies of Smoked Marijuana in 76 Veterans With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: PTSD
marijuana
cannabis
sleep
THC
CBD
Lead sponsor: Multidisciplinary Association for Psychedelic Studies
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This pilot study gathered preliminary evidence of the safety and efficacy of four potencies of smoked cannabis to manage chronic, treatment-resistant PTSD among veterans: (1) High THC/ Low CBD (High THC), (2) Low THC/High CBD (High CBD), (3) High THC/ High CBD (THC/CBD) and (4) Low THC/Low CBD (placebo). The study will produce preliminary evidence to help elucidate the potential effects of THC, CBD, or a combination of both constituents to reduce PTSD symptoms. Smoked cannabis will be tested in two stages of three weeks each (Stage 1 and Stage 2), with a two-week cessation period after each stage, verified by blood/urine cannabinoid analysis. The primary objective was to compare three active concentrations of smoked cannabis and placebo on PTSD symptom severity measured by CAPS-5 total severity scores during Stage 1.

Detailed description: PTSD is a serious, worldwide public health problem resulting from traumatic experiences such as sexual assault, war, or abuse. PTSD is associated with high rates of psychiatric and medical co-morbidity, disability, suffering, and suicide. Despite available treatments for PTSD, many individuals continue to experience marked PTSD symptoms following treatment. In response to overwhelming demand for new treatments, several U.S. states have passed laws allowing the medical use of cannabis by individuals with PTSD.

Emerging observational and early clinical evidence suggest that cannabis may have the potential to reduce or ameliorate a number of symptoms experienced by those with PTSD, including sleep difficulty and anxiety. Indeed, some evidence has suggested that delta-9-tetrahydrocannabinol (THC) may serve to reduce nightmares among those with PTSD, while other studies have shown anxiolytic effects of cannabidiol (CBD). However, there have been no randomized controlled trials of cannabis, in any form, for PTSD.

The present triple-blind, randomized, placebo-controlled crossover trial aims to examine the safety and efficacy of four types of cannabis (i.e., high THC, low CBD; high CBD, low THC; equal ratio THC/CBD; and placebo) among 76 military veterans with chronic treatment-resistant PTSD of at least six months' duration. The study will produce preliminary evidence to help elucidate the contribution of THC, CBD, or a combination of both constituents to potential attenuation of PTSD symptoms.

Smoked cannabis was tested in two stages lasting three weeks each (Stage 1 and Stage 2), with a two-week cessation after each stage, verified by blood/urine cannabinoid analysis. The primary objective was to compare three active concentrations of smoked cannabis and placebo on PTSD symptom severity measured by CAPS-5 total scores during Stage 1.

Study participants received one of four different types of cannabis during Stage 1 with crossover and re-randomization, less the placebo cannabis, at Stage 2. The four potencies of cannabis were High THC/ Low CBD (High THC), Low THC/High CBD (High CBD), High THC/High CBD (THC/CBD) and Low THC/Low CBD (placebo). "High" is defined as marijuana containing a target of 7-15% concentration by weight of the respective cannabinoid and "Low" is defined as \< 2% concentration by weight. Prior to each stage, participants completed two introductory sessions where they were trained on cannabis self-administration. During each stage, participants were provided 1.8 grams of cannabis daily to smoke ad libitum. Each stage was followed by a two-week cessation period.

The primary objective was to compare three active concentrations of smoked cannabis and placebo on PTSD symptom severity measured by CAPS-5 total severity scores during Stage 1.

Eligibility criteria: Inclusion Criteria:

* Have chronic treatment-resistant PTSD of at least six months duration.
* Have PTSD of at least moderate severity at the time of baseline assessment.
* Be a military veteran with PTSD.
* Be at least 18 years old.
* Be willing to commit to medication dosing and delivery method, to completing evaluation instruments, and attending all study visits.
* Agree to use only cannabis provided by site staff and agree to required cessation periods for the duration of the study.
* Report no current hazardous cannabis use and completely abstain from cannabis during the 2-week baseline assessment period (verified via urine and/or blood cannabinoid concentrations).
* Agree to video record all cannabis administrations and provide video to the site staff for review during study participation.
* Agree to keep all cannabis provided by site staff securely stored in the provided lock box and not to share/distribute cannabis to any other individual.
* Be stable on any pre-study medications and/or psychotherapy regimen for PTSD prior to study entry, agree to notify their physician/clinician about participation in the study, and agree to report any changes in medication or psychotherapy treatment regimen during the study, to site staff.
* If female and of childbearing potential, agree to use an effective form of birth control during study participation and may only be allowed to enroll and continue in the study based on a negative pregnancy test.
* Be proficient in reading and writing in English and able to effectively communicate with site staff.
* Agree not to participate in any other interventional clinical trials during the study

Exclusion Criteria:

* Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study.
* Have any allergies to cannabis or contraindication for smoking of cannabis
* Are abusing illegal drugs.
* Are not able to give adequate informed consent.
* Are not able to attend face-to-face visits or those who plan to move out of the area within the treatment period.
* Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control.

Primary outcomes:
measure: Baseline CAPS-5 Total Severity Score
timeFrame: Baseline (3 weeks after randomization)
measure: Stage 1 Primary Endpoint CAPS-5 Total Severity Scores (Visit 5)
timeFrame: Visit 5 (between end of week 3 and start of week 4) of Stage 1
measure: Change in CAPS-5 Total Severity Scores From Baseline to Stage 1 Primary Endpoint (Visit 5)
timeFrame: Baseline (3 weeks after randomization) to Primary Endpoint (Visit 5, between end of week 3 and start of week 4)
Secondary outcomes:
measure: Change in PTSD Checklist (PCL-5) From Baseline to Stage 1 Primary Endpoint
timeFrame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
measure: Change in Inventory of Depression and Anxiety (IDAS) Social Anxiety Total Scores From Baseline to Stage 1 Primary Endpoint
timeFrame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
measure: Change in Inventory of Psychosocial Functioning (IPF) From Baseline to Stage 1 Primary Endpoint
timeFrame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
measure: Change in Inventory of Depression and Anxiety (IDAS) General Depression Total Scores From Baseline to Stage 1 Primary Endpoint
timeFrame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
measure: Change in Insomnia Severity Index (ISI) Scores From Baseline to Stage 1 Primary Endpoint
timeFrame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
Other outcomes:
measure: Actigraph Change in Sleep Efficiency
timeFrame: Change in sleep efficiency from baseline to end of 4-week treatment period (visit 6)
Locations:
city: Phoenix
country: United States
facility: Scottsdale Research Institute
state: Arizona
Study officials:
affiliation: President of Scottsdale Research Institute
name: Sue Sisley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bonn-Miller MO, Sisley S, Riggs P, Yazar-Klosinski B, Wang JB, Loflin MJE, Shechet B, Hennigan C, Matthews R, Emerson A, Doblin R. The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial. PLoS One. 2021 Mar 17;16(3):e0246990. doi: 10.1371/journal.pone.0246990. eCollection 2021.