Details of study characteristics, critical appraisal, and study findings are located in Appendices 2, 3, and 4, respectively.
Quantity of Research Available
A total of 206 citations were identified in the literature search. Following screening of titles and abstracts, 197 citations were excluded and nine potentially relevant reports from the electronic search were retrieved for full-text review. Four potentially relevant publications were retrieved from the grey literature search. Of these 13 potentially relevant articles, 12 publications were excluded for various reasons, while one publication met the inclusion criteria and was included in this report. Appendix 1 describes the PRISMA flowchart of the study selection.
Summary of Study Characteristics
One systematic review met the inclusion criteria for this Rapid Response.11 No additional randomized controlled trials (RCTs) or non-randomized studies not already included in the systematic reviews met the inclusion criteria for the review (Table A1, Appendix 2).
Country of Origin
The systematic review was performed by authors from the United States11 (Table A1, Appendix 2).
Patient Population
The systematic review searched for studies published between January 1980 and March 2015 and included 13 studies, six of which evaluated either oral THC, nabilone, or smoked marijuana in the PTSD population, with sample sizes ranging from 10 to 104 participants.11 The included studies were published between 2009 and 2015. The seven remaining studies evaluated oral THC in Tourette’s Syndrome and for agitation in the Alzheimer’s population (these populations are out of scope and therefore results are not reported in this review). Of the six included PTSD studies, one included patients (n = 104) at a mental health and correctional facility that treated adult male offenders with serious mental illness. Approximately 90% of these patients were diagnosed with PTSD, and many had varying comorbid diagnoses, including mood, psychotic and substance use disorders. Three of the studies included a total of 119 soldiers, combat veterans, or military personnel. In the remaining two studies (n = 57 participants), the nature of the PTSD was not provided (Table A1, Appendix 2).
Interventions and Comparators
Of the six studies in the PTSD population, three studies administered nabilone and the dose ranged from 0.5 mg to 6 mg per day (n = 2 studies), and from 0.5 mg to 3 mg (n = 1 study).11 One of these studies compared nabilone with placebo, while the other two studies were retrospective chart reviews and did not have a control group. Two prospective studies administered smoked marijuana (no control group), one of which the dosage was described as ad lib, with approximately 23% THC and less than 1% cannabidiol. In the other smoked marijuana study, participants smoked approximately 2 g to 3 g per day. One study administered oral THC (no control group), range 0.5 mg to 5 mg per day. In at least three studies, the intervention was administered as an add-on to other pharmacologic treatment. Details regarding these treatments were not provided, although for two studies the medications were described as psychotropic (Table A1, Appendix 2).
Outcomes
The systematic review evaluated the strength of the evidence for the efficacy of marijuana and other cannabinoids on the symptoms of PTSD.11 The included studies reported on nightmare quantity and intensity, sleep quality and quantity, daytime flashbacks, night sweats, quality of life, and pain. Limited information was provided on adverse events for the included studies. Outcomes were generally assessed through the administration of questionnaires such as the Clinician Administered PTSD Scale (CAPS), which evaluates PTSD symptoms (Table A1, Appendix 2).
Summary of Critical Appraisal
Based on the AMSTAR assessment, the systematic review appeared to be satisfactory. The narrative summary appeared to be an appropriate approach given the differences in the study populations of the identified studies (e.g., patients with comorbid mental health conditions), the variations in study design (one RCT, two retrospective chart reviews, and three prospective observational studies, often with limited data provided), and variations in the form and dosage of the intervention. The scientific quality of the included studies was thoroughly assessed and documented, and used appropriately in forming conclusions, with two authors independently rating the studies on quality, consistency, generalizability, and effect size using GRADE methodology. Only one database was searched, although this limitation was mitigated to some extent in that the authors attempted to identify other studies and conference abstracts using cross-referencing. It was not clear whether two investigators had selected studies and extracted data. The inclusion and exclusion criteria were not stated, and very limited details regarding the characteristics of the included studies were provided (Table A2, Appendix 3).
Summary of Findings
1. What is the clinical effectiveness of medical marijuana for the treatment of post-traumatic stress disorder in adults?
The systematic review11 included two studies in which smoked marijuana was the intervention, and one study evaluating oral THC. All three studies reported improvement in the CAPS total score or subscores, two of which reported significant improvement (the third was a conference abstract that did not provide a statistical analysis). One study also reported a significant improvement in sleep quality, frequency of nightmares, and the Clinical Global Impressions scale. The conference abstract that did not include a statistical analysis also reported an improvement in quality of life and pain scores, as well as a discontinuation or lowering of dosage for sedatives and painkillers. While the findings suggested that smoked marijuana and oral THC are efficacious in treating some symptoms of PTSD, the authors cautioned that the overall GRADE of evidence was very low. Based on these findings and an evaluation of the quality of evidence, the authors concluded that there is very low-quality evidence to support the efficacy of using oral THC or smoked marijuana in treating nightmares and symptom severity in adults with PTSD and suggested caution in using medical marijuana for these disorders (Table A3, Appendix 4).
2. What is the clinical effectiveness of synthetic cannabinoids for the treatment of post-traumatic stress disorder in adults?
The systematic review11 included three studies evaluating nabilone. One cross-over RCT evaluated 10 patients over 16 weeks, and reported significant improvement in nightmares, the Clinical Global Impressions score, and well-being as measured by the General Well-Being Questionnaire. One of two retrospective chart reviews reported a significant decrease in nightmares, a significant increase in hours of sleep, and in Global Assessment of Functioning scores. In the remaining retrospective chart review, 72% of participants reported a cessation of nightmares or reduction in nightmare intensity, a subjective improvement in sleep time and quality, and a reduction in daytime flashbacks and night sweats. In this study, nabilone was discontinued in 28% of patents due to side effects. Side effects were described as mild to moderate and included lightheadedness, forgetfulness, dizziness and headache. While the findings suggested that nabilone is efficacious in treating some symptoms of PTSD, the authors cautioned that the overall GRADE of evidence is very low. (Table A3, Appendix 4).
3. What are the evidence-based guidelines regarding the use of medical marijuana or synthetic cannabinoids in adult patients with post-traumatic stress disorder?
No guidelines regarding the use of medical marijuana or synthetic cannabinoids in adult patients with PTSD were identified.
Limitations
While all of the studies included in the systematic review reported improvement across a number of outcomes, the authors caution that the quality of the evidence is very low based on a detailed GRADE assessment. Of the six included studies, only one was an RCT, and it followed 10 patients for 16 weeks (crossover design, seven weeks for either the intervention or placebo, with a two-week washout). Two of the included studies were unpublished with limited information provided, and statistical analysis was not available. One of the studies included participants from a mental health and correctional facility that treated adult male offenders with serious mental illness. While 90% of these patients were diagnosed with PTSD, the study included patients with varying comorbid diagnoses, and 91% met criteria for marijuana dependence. Hence the results of this study may not be generalizable to the broader PTSD population. Three of the included studies were conducted in soldiers, veterans, or other military personnel, again impacting the generalizability of the findings to the broader PTSD population. For two of the included studies the nature of the trauma for the study participants was not stated. In at least three studies, the intervention was administered as an adjunct to other pharmacologic treatment (in two cases described as psychotropic), and hence it is difficult to evaluate the effect of the marijuana intervention specifically. Of the six included studies, side effects were reported for one study. The authors noted many factors that contribute to the low grade of evidence for the selected outcomes, including non-standardized administration of the intervention, concomitant use of other medications, lack of blinding or control groups, selective or incomplete reporting, inadequate or unreported statistical analysis, and poor generalizability.
