AEF0117, the first signaling-specific CB1 receptor inhibitor, reduced cannabis positive effects by up to 38% and decreased self-administration in people with cannabis use disorder.
Addiction medicine specialists, pharmacologists, and clinical researchers in substance use disorder treatment.
38% reductionin cannabis positive subjective effects with AEF0117 1 mg vs. placebo in people with cannabis use disorder
What the researchers found
In phase 2a trials, AEF0117 at 1 mg reduced cannabis positive subjective effects by 38% versus placebo (p<0.04) and reduced self-administration (p<0.05), without precipitating withdrawal or significant adverse effects.
Why it matters
Cannabis use disorder has no approved pharmacotherapy. AEF0117 represents an entirely new drug class that selectively blocks THC effects without the problems of previous CB1 blockers like rimonabant.
The numbers in context
Phase 1: 40 participants (single-ascending-dose) and 24 (multiple-ascending-dose). Phase 2a: 29 CUD participants in two dose cohorts (0.06 mg, n=14; 1 mg, n=15). CBD positive effects reduced by 19% (0.06 mg) and 38% (1 mg) vs. placebo.
How the study worked
Three randomized controlled trials: single-ascending-dose and multiple-ascending-dose phase 1 trials in healthy volunteers, and a double-blind, placebo-controlled, crossover phase 2a trial in volunteers with CUD.
Who was studied
Healthy volunteers (phase 1, n=64) and volunteers with cannabis use disorder (phase 2a, n=29).
What this study cannot tell us
Small sample sizes in all trials. Phase 2a was short-term. Laboratory self-administration may not reflect real-world use. Long-term safety and efficacy not yet established.
How to read the evidence
Phase 1 and 2a randomized controlled trials provide early clinical evidence of safety and efficacy; larger trials needed.
When this study was published
Recent early-phase clinical trials (registered on ClinicalTrials.gov).
The bigger picture
Unlike rimonabant, which was withdrawn due to psychiatric side effects, AEF0117 selectively inhibits only certain CB1 signaling pathways, potentially offering treatment for CUD without the risks that plagued earlier CB1-targeting drugs.
Replication
Early-phase trials; efficacy needs confirmation in larger studies.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Will the efficacy hold in larger, longer-term clinical trials?
- Could this drug help with other substance use disorders involving the endocannabinoid system?
Read the original research
Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.
Nature medicine, 29(6), 1487-1499
Citation
Haney, Margaret; Vallée, Monique; Fabre, Sandy; Collins Reed, Stephanie; Zanese, Marion; Campistron, Ghislaine; Arout, Caroline A; Foltin, Richard W; Cooper, Ziva D; Kearney-Ramos, Tonisha; Metna, Mathilde; Justinova, Zuzana; Schindler, Charles; Hebert-Chatelain, Etienne; Bellocchio, Luigi; Cathala, Adeline; Bari, Andrea; Serrat, Roman; Finlay, David B; Caraci, Filippo; Redon, Bastien; Martín-García, Elena; Busquets-Garcia, Arnau; Matias, Isabelle; Levin, Frances R; Felpin, François-Xavier; Simon, Nicolas; Cota, Daniela; Spampinato, Umberto; Maldonado, Rafael; Shaham, Yavin; Glass, Michelle; Thomsen, Lars Lykke; Mengel, Helle; Marsicano, Giovanni; Monlezun, Stéphanie; Revest, Jean-Michel; Piazza, Pier Vincenzo. (2023). Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.. Nature medicine, 29(6), 1487-1499. https://doi.org/10.1038/s41591-023-02381-w