A review of endocannabinoid-based approaches to tobacco use disorder found that CB1 neutral antagonists and FAAH inhibitors showed the most promise for smoking cessation and relapse prevention.
Addiction researchers, pharmacologists, clinicians working on smoking cessation
CB1 neutral antagonists and FAAH inhibitors showed positive effects across multiple addiction-related measures
What the researchers found
CB1 receptor neutral antagonists and fatty acid amide hydrolase (FAAH) inhibitors demonstrated positive effects across multiple addiction-related factors including nicotine reinforcement, cue-induced reinstatement, and withdrawal. The CB1 inverse agonist rimonabant was effective for cessation but caused psychiatric side effects.
Why it matters
Tobacco use disorder remains a leading cause of preventable death, and existing treatments have high relapse rates. The endocannabinoid system offers novel targets that could complement current cessation strategies.
The numbers in context
Rimonabant (CB1 inverse agonist) was effective for smoking cessation but withdrawn due to psychiatric adverse effects. CB1 neutral antagonists and FAAH inhibitors showed positive effects across several addiction-related endpoints.
How the study worked
Expert review examining studies on endocannabinoid modulation (CB1 receptor, CB2 receptor, anandamide, and 2-AG pathways) across addiction-related factors: nicotine reinforcement, reinstatement of drug seeking, withdrawal severity, and executive function.
What this study cannot tell us
Much of the evidence is from preclinical models; few human clinical trials exist for CB1 neutral antagonists or FAAH inhibitors in tobacco cessation specifically; the field is still at an early stage.
How to read the evidence
Expert review with largely preclinical evidence; few human clinical trials in this specific application.
When this study was published
Published in 2020.
The bigger picture
The failure of rimonabant highlighted the need for endocannabinoid-based drugs that can reduce addiction without the mood-related side effects. Newer approaches targeting FAAH or using neutral CB1 antagonists may thread this needle.
Questions still open
- Could FAAH inhibitors serve as both cessation aids and relapse prevention agents? Would combining endocannabinoid modulators with existing treatments improve outcomes?
Common questions
What happened with rimonabant?
How might the endocannabinoid system help with quitting smoking?
Read the original research
Novel therapeutic and drug development strategies for tobacco use disorder: endocannabinoid modulation.
Expert opinion on drug discovery, 15(9), 1065-1080
Citation
Butler, Kevin; Le Foll, Bernard. (2020). Novel therapeutic and drug development strategies for tobacco use disorder: endocannabinoid modulation.. Expert opinion on drug discovery, 15(9), 1065-1080. https://doi.org/10.1080/17460441.2020.1767581
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