Classic psychedelics such as LSD and psilocybin are generally well tolerated in clinical or research settings, though serious adverse events do occur. In a systematic review and meta-analysis of 214 studies, serious adverse events were reported for no healthy participants and for about 4% of participants with preexisting neuropsychiatric disorders, including worsening depression, suicidal behavior, psychosis, and convulsive episodes. Nonserious adverse events requiring medical intervention, such as paranoia and headache, were rare. In contemporary research, no deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders were reported after high-dose psychedelic administration. However, the quality of adverse event monitoring and reporting varied significantly across studies.
Psychedelic treatments, particularly psilocybin and MDMA, show promise for psychiatric conditions, with psilocybin having strongest evidence for treatment-resistant depression and MDMA for post-traumatic stress disorder. These treatments combine limited drug sessions with psychotherapy, working through neural and psychological pathways that are not fully understood. While well-tolerated under controlled conditions, methodological issues like unblinding and homogeneous trial populations complicate evidence interpretation. Scalability is challenging due to required extensive support, though group administration may help. Future priorities include standardizing adverse event assessment and showing durable benefits in diverse populations.
A commentary responds to a proposed framework for assessing adverse events in psychedelic-assisted therapies, which includes spiritual, existential, religious, and theological impacts. The authors argue that adverse event assessment in psychedelic clinical trials should match the rigor and standards of other research areas, and emphasize the need for transparency and accessibility in reporting. The commentary discusses the framework's feasibility and various assessment methods, focusing on ensuring systematic and unbiased evaluation of adverse events.