Psychedelics, Safety and Clinical Trial Design

Abstract

Objectives: To investigate the safety of psychedelics for humans, to identify the limitations of the current evidence and to indicate how gaps and limitations may be addressed in future clinical trial design. Methodology: I completed a narrative review of the literature to investigate the safety profile and known adverse effects of psychedelics, with a specific focus on psilocybin and magic mushrooms. Results: Psychedelics can be accompanied by known adverse experiences, such as increased heart rate, blood pressure and breathing rate, headaches, and transient psychological distress. For some people, negative effects persist for days or weeks, usually depending on how long the transient distress lasts. Evidence for the empirical validation of Hallucinogen Persisting Perception Disorder (HPPD) is scant, and the diagnosis itself has come into question. The risks of negative experiences can be reduced by appropriate dosage, setting, preparation and support, as well as by not taking multiple doses or combining with other substances. Some medications do not mix well with psychedelics, including many anti-depressants. Psychedelics can be healing and beneficial, but they are powerful and often involve an ordeal, like many journeys. Clinical trials investigating psychedelics have established exclusion criteria to ensure appropriate subject selection and provide significant preparation, support and a setting to mitigate the known risks. Trials using psychedelics have established safety, tolerability and suggest efficacy; however, stage 3 clinical trials to establish effectiveness through a randomized control methodology are just now beginning. Conclusion: Psychedelics are relatively safe, with a low toxicity and risk profile; however, certain adverse experiences such as transient psychological distress and post-treatment headaches are common, and in some cases can be severe and persisting. Risks are mitigated through appropriate candidate selection, preparation, setting and support. The scientific literature is limited, and stage 3 clinical trials are needed to establish effectiveness for a wide range of potential treatment patients.