The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial
Marcel O. Bonn‐Miller, Sue Sisley, Paula Riggs, Berra Yazar‐klosinski, Julie B. Wang, Mallory Loflin, Benjamin Shechet, Colin Hennigan, Rebecca Matthews, Amy Emerson, Rick Doblin
PLoS ONE March 17, 2021 DOI: 10.1371/journal.pone.0246990 via OpenAlex
Summary
A randomized placebo-controlled trial tested three concentrations of smoked cannabis (high THC, high CBD, THC+CBD) against placebo in military veterans with PTSD. Over three weeks, all groups including placebo showed significant improvements in PTSD symptom severity, but none of the active cannabis concentrations outperformed placebo statistically. The treatments were generally well tolerated. This preliminary trial did not find evidence that smoked cannabis is more effective than placebo for PTSD symptoms in the short term, highlighting the need for further well-powered studies.
Study at a glance
| Characteristics | Randomized controlled trial, double-blind, cross-over Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Military veterans with PTSD |
| Intervention | High CBD |
| Dose | High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD; placebo = < 0.03% THC and < 0.01% CBD |
| Duration | 3-week treatment, 2-week washout |
| Topics | Cannabis |
| Keywords | Placebo Randomized controlled trial Internal medicine Psychiatry |
| Citations | 129 |
| Registration | NCT02759185 |
| Key finding | No active cannabis concentration significantly outperformed placebo in reducing PTSD symptom severity over three weeks. |
Abstract
IMPORTANCE: There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. OBJECTIVE: The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans. METHODS: The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1. RESULTS: The study did not find a significant difference in change in PTSD symptom severity between the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated. CONCLUSIONS AND RELEVANCE: The present study is the first randomized placebo-controlled trial of smoked cannabis for PTSD. All treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled and adequately powered studies with cannabis suitable for FDA drug development are needed to determine whether smoked cannabis improves symptoms of PTSD. TRIAL REGISTRATION: Identifier: NCT02759185; ClinicalTrials.gov.