Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting

•Recent psychedelic use was associated with 55% reduced odds of daily opioid use.•This is the first longitudinal study to link psychedelic use with lower daily opioid use.•More studies are needed to elucidate the therapeutic potential of psychedelics. Research into the therapeutic and naturalistic uses of psychedelics for improving outcomes related to mental health disorders has generated increasing interest in recent years. While controlled clinical trials of psychedelics have signaled benefits for treating substance use disorders, this area has not been well studied in the context of naturalistic psychedelic use. This study sought to investigate the possible relationship between recent naturalistic psychedelic use and subsequent daily illicit opioid use among people who use drugs (PWUD). Data (2006–2018) were drawn from three harmonized prospective cohorts of community-recruited PWUD in Vancouver, Canada. We used multivariable generalized linear mixed-effects modeling (GLMM) to estimate the independent association between psychedelic use and subsequent daily illicit opioid use. Among 3813 PWUD at baseline, 1093 (29%) reported daily use of illicit opioids and 229 (6%) reported psychedelic use in the past six months. Over study follow-up after adjusting for a range of potential confounders, psychedelic use remained independently associated with a significantly reduced odds of subsequent daily opioid use (Adjusted Odds Ratio: 0.45; 95% Confidence Interval: 0.29 to 0.70). While confirmation in other settings is required, these findings align with growing evidence that psychedelic use may be associated with detectable reductions in subsequent substance use including illicit opioid use.