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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
80
Three weeks of smoking cannabis containing more THC than CBD with amount smoked limited to no more than 1.8 g per day.
Three weeks of smoking cannabis containing more CBD than THC with amount smoked limited to no more than 1.8 g per day.
Three weeks of smoking cannabis containing equal amounts of THC and CBD with smoking limited to no more than 1.8 g per day.
Three weeks of smoking cannabis with low levels of THC and CBD with smoking limited to no more than 1.8 per day.
Scottsdale Research Institute
Phoenix, Arizona, United States
Baseline CAPS-5 Total Severity Score
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a CAPS-5 total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance), and D (hypervigilance), and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
Time frame: Baseline (3 weeks after randomization)
Stage 1 Primary Endpoint CAPS-5 Total Severity Scores (Visit 5)
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a CAPS-5 total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance), and D (hypervigilance); and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
Time frame: Visit 5 (between end of week 3 and start of week 4) of Stage 1
Change in CAPS-5 Total Severity Scores From Baseline to Stage 1 Primary Endpoint (Visit 5)
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician administered and scored assessment of PTSD symptoms via structured interview based upon PTSD diagnosis in DSM-5. It contains symptom subscales, a CAPS-5 total severity score, and a diagnostic score. The total severity score is a sum of symptom frequency and intensity scores for the subscales B (re-experiencing), C (avoidance), and D (hypervigilance); and ranges from 0 to 136, with higher scores indicating greater severity of PTSD symptoms.
Time frame: Baseline (3 weeks after randomization) to Primary Endpoint (Visit 5, between end of week 3 and start of week 4)
Change in PTSD Checklist (PCL-5) From Baseline to Stage 1 Primary Endpoint
The PTSD Checklist (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms. Participants indicate how much distress they have experienced due to various PTSD symptoms on a five-point Likert-type scale (0=not at all, 4=extremely). The total PCL-5 score (a sum of all 20 items) ranges from 0 to 80, with higher scores indicating greater symptom severity.
Time frame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
Change in Inventory of Depression and Anxiety (IDAS) Social Anxiety Total Scores From Baseline to Stage 1 Primary Endpoint
The Inventory of Depression and Anxiety (IDAS) is a 64-item self-report measure of non-overlapping scales that assess specific depression and anxiety symptoms. Respondents indicate on a scale of 1 (not at all) to 5 (extremely) how much they have felt or experienced several symptoms in the past two weeks. The IDAS consists of 10 symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions. Items that assess social anxiety are summed and range from 5 to 25 with higher scores indicating greater anxiety symptoms.
Time frame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
Change in Inventory of Psychosocial Functioning (IPF) From Baseline to Stage 1 Primary Endpoint
The Inventory of Psychosocial Functioning (IPF) is an 80-item measure that was developed for use among individuals with PTSD. It assesses current psychosocial functioning across seven domains: romantic relationships, family, work, friendships, parenting, education, and self-care. Items are scored on a 0 (never) to 6 (always) scale. Summation of scores across domains yields a total score for psychosocial functioning, with higher scores indicating greater functional impairment.
Time frame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
Change in Inventory of Depression and Anxiety (IDAS) General Depression Total Scores From Baseline to Stage 1 Primary Endpoint
The Inventory of Depression and Anxiety (IDAS) is a 64-item self-report measure of non-overlapping scales that assess specific depression and anxiety symptoms. Respondents indicate on a scale of 1 (not at all) to 5 (extremely) how much they have felt or experienced several symptoms in the past two weeks. The IDAS consists of 10 symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions. Items that assess general depression are summed and range from 20 to 100 with higher scores indicating greater depressive symptoms.
Time frame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
Change in Insomnia Severity Index (ISI) Scores From Baseline to Stage 1 Primary Endpoint
The Insomnia Severity Index (ISI) is a brief self-reported measure of insomnia. It consists of seven questions, with responses made on a five-point Likert scale. Three items address difficulty at sleep onset, maintaining sleep, and early waking, and four questions address perceived quality of sleep and effects of sleep difficulties on daily function. Questions are summed into a total score that ranges from 0 to 28 and can be interpreted as ranging from no signs of insomnia to severe insomnia. Higher scores indicate more severe insomnia.
Time frame: Baseline (3 weeks after randomization) to Stage 1 Primary Endpoint (Visit 6, 3 weeks post self-administration and prior to cessation)
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