Associations between classic psychedelics and nicotine dependence in a nationally representative sample

Tobacco use is the single largest cause of preventable death worldwide, but none of the established treatments aimed at smoking cessation work for a majority of smokers. As such, there is an urgent need for interventions capable of reliably treating nicotine addiction. The use of classic psychedelics has been associated with lower odds of many forms of substance dependence. Here we tested whether lifetime use of classic psychedelics (tryptamine, lysergamide, and phenethylamine) is associated with lower odds of current nicotine dependence. We tested these associations in a sample of 214,505 adult participants in the National Survey on Drug Use and Health (2015-2019) using multivariable logistic regression models. Lifetime psilocybin use was associated with reduced odds of odds of current nicotine dependence (aOR 0.87-0.93). Lifetime use of peyote and mescaline also conferred reduced odds of multiple subdomains of a main nicotine dependence measure (Nicotine Dependence Syndrome Scale [NDSS]) (aOR 0.79-0.91). Conversely, lifetime use of LSD was associated with increased odds of nicotine dependence (aOR 1.17-1.24). Psilocybin, mescaline, and peyote use are associated with lowered odds of nicotine dependence. Experimental studies are needed to establish whether these associations are causal. These results make the case for further research into the efficacy of both tryptamine and phenethylamine psychedelics in promoting smoking cessation.