Background: Psychedelic‐assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic‐assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life‐threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks.
Objectives: To assess the benefits and harms of psychedelic‐assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life‐threatening diseases.
Search methods: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions.
Selection criteria: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance‐induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions.
Data collection and analysis: We used the standard methodological procedures expected by Cochrane.
Main results: We included six studies in the review, which evaluated two different interventions: psychedelic‐assisted therapy with classical psychedelics (psilocybin (‘magic mushrooms’) and lysergic acid diethylamide (LSD)), and psychedelic‐assisted therapy with 3,4‐methylenedioxymethamphetamine (MDMA or ‘Ecstasy’). The studies randomised 149 participants with life‐threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic‐assisted therapy.
Implications for practice: Psychedelic‐assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life‐threatening disease. Psychedelic‐assisted therapy seemed to be well tolerated, with no treatment‐emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries.
Implications for research: The risk of bias due to ‘unblinding’ (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross‐over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.