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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 PTSD |
| Keywords | Placebo Randomized controlled trial Pathology Alternative medicine |
| Citations | 129 |
| Registration | NCT02759185 |
| Key findings | 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.
Comparable studies
Other randomized controlled trials on PTSD, most cited first.
Citations in the library
Cited by 22
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry. Expert Review of Neurotherapeutics 2022
- High-Concentration Delta-9-Tetrahydrocannabinol Cannabis Products and Mental Health Outcomes : A Systematic Review. Annals of Internal Medicine October 1, 2025
- Novel Pharmacologic and Other Somatic Treatment Approaches for Posttraumatic Stress Disorder in Adults: State of the Evidence. American Journal of Psychiatry December 1, 2024
- Cannabis-assisted psychotherapy for complex dissociative posttraumatic stress disorder: A case report Frontiers in Psychiatry February 9, 2023
and 17 more in the library
Cites 5
- The Long-Term, Prospective, Therapeutic Impact of Cannabis on Post-Traumatic Stress Disorder. Cannabis and Cannabinoid Research April 2022
- Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. Journal of Affective Disorders September 1, 2020
- Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption. European Neuropsychopharmacology June 2015
- The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology January 2015
- Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder. Clinical drug investigation August 2014