A systematic review and narrative summary of the therapeutic potential of classic serotonergic psychedelics for smoking cessation and reduction

Background: Classic serotonergic psychedelics are 5-HT2A partial agonists that induce non-ordinary states of consciousness. Many have demonstrated anti-addictive properties; however, their impact on smoking behaviors remains under-researched. This review provides a synthesis of the therapeutic potential of these compounds in promoting smoking cessation and reduction.

Methods: A systematic review of peer-reviewed studies on psychedelics and smoking outcomes, published in English, was conducted. Database searches of PubMed, CINAHL, PsycINFO, and EMBASE resulted in 3547 records. ASReview, an open-source machine-learning tool, was used to improve the screening process. Abstract and initial review screening excluded 2336 articles, leaving 29 full-text articles for review. After further exclusion based on the inclusion of psychedelics and reported outcomes, eight studies were included in the analysis. All studies were assessed for risk of bias using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.

Results: Heterogeneity in the data was observed. All studies showed a serious risk of bias. Psilocybin was the most frequently reported compound ( n = 7), followed by lysergic acid diethylamide (LSD; n = 5), mescaline ( n = 4), ayahuasca ( n = 4), peyote ( n = 2), and N,N-dimethyltryptamine ( n = 1). Psilocybin, LSD, and ayahuasca revealed preliminary therapeutic potential for facilitating smoking cessation.

Conclusions: Current literature on psychedelics’ anti-addictive effects on smoking behaviors is promising but limited by weak study designs and low generalizability. Future research should allow for stronger sampling methods to improve statistical power and include comparative groups within experimental or quasi-experimental designs to strengthen inference for causal mechanisms between drug and nondrug influences on smoking outcomes.