First placebo-controlled trial of smoked cannabis for PTSD found no treatment outperformed placebo
In the first randomized placebo-controlled trial of smoked cannabis for PTSD in veterans, all groups improved significantly but none of the three active cannabis preparations outperformed placebo.
Quick Facts
What This Study Found
Three cannabis preparations (high THC, high CBD, and balanced THC+CBD) were all well tolerated and all groups showed significant PTSD symptom improvement, but no active treatment was statistically better than placebo after three weeks of use.
Key Numbers
80 participants in Stage 1; 74 in Stage 2; high THC (~12% THC, <0.05% CBD); high CBD (11% CBD, 0.50% THC); THC+CBD (~7.9% THC, 8.1% CBD); placebo (<0.03% THC)
How They Did This
Double-blind, cross-over design with 80 veterans randomized to three weeks of active treatment or placebo in Stage 1, then re-randomized to a different active treatment in Stage 2 after a 2-week washout. Primary outcome was change in PTSD symptom severity.
Why This Research Matters
Despite widespread veteran use of cannabis for PTSD, this first rigorous trial found no evidence that smoked cannabis outperforms placebo. The strong placebo response complicates future trial design.
The Bigger Picture
The strong placebo response across all groups raises questions about whether expectation effects drive much of the reported benefit of cannabis for PTSD, a finding with implications for both research design and clinical practice.
What This Study Doesn't Tell Us
Brief 3-week treatment period, difficulty blinding smoked cannabis (participants may detect active vs placebo), relatively small sample, cross-over design may introduce carryover effects.
Questions This Raises
- ?Would longer treatment periods show different results?
- ?Can smoked cannabis trials ever be adequately blinded?
- ?Would different cannabis formulations or delivery methods show superiority over placebo?
Trust & Context
- Key Stat:
- No active cannabis preparation outperformed placebo for PTSD symptoms
- Evidence Grade:
- Randomized placebo-controlled crossover trial, though limited by small size and short duration
- Study Age:
- Published in 2021. This landmark trial established that rigorous cannabis-for-PTSD research is feasible.
- Original Title:
- The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.
- Published In:
- PloS one, 16(3), e0246990 (2021)
- Authors:
- Bonn-Miller, Marcel O(23), Sisley, Sue, Riggs, Paula(2), Yazar-Klosinski, Berra, Wang, Julie B, Loflin, Mallory J E, Shechet, Benjamin, Hennigan, Colin, Matthews, Rebecca, Emerson, Amy, Doblin, Rick
- Database ID:
- RTHC-03017
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
Does smoked cannabis help PTSD?
In this first placebo-controlled trial, all groups (including placebo) showed significant PTSD improvement, but no cannabis preparation was statistically better than placebo after three weeks.
Were different cannabis types tested?
Yes. High-THC, high-CBD, and balanced THC/CBD preparations were all tested against placebo. None outperformed placebo, though all were well tolerated.
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Cite This Study
https://rethinkthc.com/research/RTHC-03017APA
Bonn-Miller, Marcel O; Sisley, Sue; Riggs, Paula; Yazar-Klosinski, Berra; Wang, Julie B; Loflin, Mallory J E; Shechet, Benjamin; Hennigan, Colin; Matthews, Rebecca; Emerson, Amy; Doblin, Rick. (2021). The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.. PloS one, 16(3), e0246990. https://doi.org/10.1371/journal.pone.0246990
MLA
Bonn-Miller, Marcel O, et al. "The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.." PloS one, 2021. https://doi.org/10.1371/journal.pone.0246990
RethinkTHC
RethinkTHC Research Database. "The short-term impact of 3 smoked cannabis preparations vers..." RTHC-03017. Retrieved from https://rethinkthc.com/research/bonn-miller-2021-the-shortterm-impact-of
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.