The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial
Bonn-Miller et al.·PLOS ONEImpact 2.8
No benefit demonstratedGRADEModerate127 citations
Samplen = 80 Pat.
Duration3 weeks of treatment in Stage 1
ControlPlacebo, double-blind, cross-over design
EndpointPTSD symptom severity
Blindingdoppelblind
DesignRCT
Cannabinoidvollspektrum
Routeinhalativ
”Key finding
No significant differences between active cannabis concentrations and placebo in the change in PTSD symptom severity after 3 weeks.
Summary
First randomized, placebo-controlled trial of smoked cannabis in PTSD; n=80 US veterans, cross-over design with 3 active concentrations (High THC ≈12%, High CBD ≈11%, THC+CBD ≈8%/8%) vs. placebo over 3 weeks. No significant difference in PTSD symptom reduction between active arms and placebo in Stage 1; all groups including placebo showed significant improvement (p<0.001 within groups). Good tolerability of all concentrations.
P
PopulationMilitary veterans with PTSD, n=80 (Stage 1), n=74 (Stage 2)
I
InterventionSmoked cannabis in three concentrations: High THC (~12% THC/<0,05% CBD), High CBD (11% CBD/0,5% THC), THC+CBD (~7,9% THC/8,1% CBD), each for 3 weeks
OutcomeNo significant difference in reduction of PTSD symptom severity between active cannabis concentrations and placebo at the end of Stage 1; all groups including placebo showed significant improvements
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
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.