6.2.2 Other adverse effects
Generally, the classic psychedelics have been deemed to be relatively low risk for adverse events,143 although there are special populations (such as older adults, and those with cardiac disorders) that have generally not been included in studies and deserve particular attention to possible cardiovascular adverse events including increased heart rate, blood pressure, and myocardial ischemia.144 As a general concern for psychedelic trials, reports of suicidal ideation (SI), non-suicidal self-injurious behavior (NSSBI), and hospitalizations for severe depression have been reported in some recent trials of psilocybin for depression as have been noted in earlier trials of psychedelics for SUDs.145These serious psychological adverse events appear rare and may reflect baseline risk for participants with mood disorders and/or SUDs, and it is uncertain what additional risks that those with chronic pain may incur. In addition, risks of hallucinogen persisting perception disorder (HPPD) a low concern but possible concern.146 Guidance suggests additional measurement of long term follow up for return to use or later overdose events which would shed light on other possible risks for psychedelics.119 Notably, rigorous reporting of adverse events across psychedelic studies has varied and deserves attention in future trial design.143
Other serotonergic psychedelics have cardiovascular risks, including QTc prolongation and possible valvular disease, warranting adequate screening and monitoring of participants with OUD, whose QTc interval may be prolonged at baseline, and who may have underlying cardiac disorders as a consequence of intravenous drug use.147,148 The concurrent use of methadone, which has relevant cardiac effects, and a psychedelic like ibogaine (also with well documented cardiac effects) may warrant additional safety monitoring.
Conclusion
Psychedelic-assisted interventions for chronic pain and OUD present a promising avenue for therapeutic innovation. Although preliminary evidence suggests potential benefits, more rigorous research is needed to establish the safety, efficacy, and optimal protocols for psychedelic-assisted interventions in these conditions. Future studies should focus on carefully selected, population-specific pain- and opioid-related outcomes, elucidating mechanisms of action, refining treatment protocols, and addressing safety concerns. This research is essential to ensure the responsible and evidence-based integration of psychedelics into research settings and potentially clinical practice. In the context of rapid attitudinal and regulatory changes regarding psychedelics, it remains to be seen whether their therapeutic potential for chronic pain and OUD — two of the most vexing problems of modern healthcare — can be fully realized.