Introduction

Psychedelic drugs, specifically serotonergic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), ayahuasca, and 3,4-methylenedioxymethamphetamine (MDMA), have shown promise in the treatment of various mental disorders. Despite their therapeutic potential, understanding the full spectrum of adverse events (AEs) associated with these treatments is crucial for making informed treatment decisions.

Methods

This mixed-methods systematic review analyzed 44 articles from clinical trials involving 598 unique patients treated with these psychedelics. The studies included a combination of quantitative and qualitative methodologies, shedding light on the safety and tolerability of these treatments.

Results

A significant finding from this review is that many studies did not systematically assess AEs, leading to a probable underreporting in the literature. Commonly reported acute AEs included nausea, headaches, and anxiety, with late AEs encompassing headaches, fatigue, low mood, and anxiety, particularly noted with MDMA. One serious AE was documented during MDMA administration, involving an increase in premature ventricular contractions requiring brief hospitalization. However, no other AEs necessitated medical intervention.

Discussion

Qualitative studies indicated that psychologically challenging experiences, often deemed adverse, could also have therapeutic benefits. This nuanced view suggests that not all AEs are detrimental to the therapeutic process. The review highlighted that a significant proportion of patients had prior experience with psychedelic drugs before participating in the studies, except for ayahuasca. This pre-exposure could influence both the experience of AEs and their reporting.

Conclusion

While serotonergic psychedelics appear to be generally well-tolerated, the poor definition and potential underreporting of AEs in the literature emphasize the need for more rigorous and systematic reporting. Acute challenging experiences may hold therapeutic value, underscoring the complexity of defining and managing AEs in psychedelic treatments. This comprehensive understanding is vital for public awareness, safety, and guiding individuals in the responsible use of psychedelics for therapeutic purposes (Breeksema et al., 2022).