REVIEW OF: Bonn-Miller MO et al, PLoS ONE 2021;16(3):e0246990

STUDY TYPE: Randomized controlled trial

More and more veterans are using cannabis to treat their PTSD symptoms, despite the lack of high-quality safety and efficacy data and the high comorbidity between PTSD and cannabis use disorder (Bryan JL et al, J Subst Abuse Treat 2021;122:108254). Researchers hoped to fill this knowledge gap by utilizing a ­double-blind crossover design to assess three preparations of smoked cannabis for the treatment of PTSD.

The study was conducted in two stages. In Stage 1, which lasted three weeks, 80 veterans with PTSD were randomized into four groups: high THC (12% THC), high CBD (11% CBD), THC+CBD (7.9% THC and 8.1% CBD), and placebo (<0.03% THC and <0.01% CBD). For context, a recent nationwide study of cannabis dispensaries found that THC and CBD content in cannabis products can vary widely. Among smoked cannabis products from medical dispensaries, the average THC content was 19.3% (range 0%–35%) and the average CBD content was 2.0% (range <5%–40%) (Cash MC et al, PLoS ONE 2020;15(3):e1230167).

Participants received 37.8 grams of the relevant study drug with no restrictions on frequency of use. The primary outcome, change in PTSD severity, was measured with the Clinician-Administered PTSD Scale (CAPS-5). At the end of Stage 1, all four groups demonstrated an overall reduction in symptoms ranging from 8.5 to 15.2 points out of a possible 80; however, the amount of symptom reduction was not significantly different between any of the groups.

In Stage 2, the remaining participants (n=74) were re-randomized into one of three active treatment groups: high THC, high CBD, and THC+CBD. This allowed for both within-subject and between-subject comparisons. All groups again experienced symptom reduction, but this time one difference reached statistical significance: The THC+CBD group had greater symptom reduction compared to the high CBD group (16.4 vs 5.7). Adverse events (AEs) throughout were characterized as mild to moderate and were similar across placebo treatment groups. A total of 13 participants discontinued the study due to an AE. Three AEs had >10% frequency: cough (12.3%), throat irritation (11.7%), and anxiety (10.4%).

The researchers behind this study acknowledged several limitations, the most significant being the fact that few participants were cannabis naïve. In fact, participants were asked to abstain from cannabis for two weeks prior to enrolling in the trial, and many were in cannabis withdrawal by the time the study started, possibly skewing results (ie, reporting improved symptoms due to alleviation of withdrawal rather than PTSD symptoms). Patient expectation likely affected the results as well, suggested by the fact that effect sizes across all groups—even placebo—were much larger than typical PTSD medication trials.

CARLAT TAKE

Despite the hint of a signal in one treatment group, this study fails to convincingly demonstrate that cannabis is an effective treatment for PTSD. The trial’s modest size and methodological shortcomings mean that further study is still warranted, but at the moment, we would discourage the use of cannabis as a PTSD treatment.