Highlights

• Classical psychedelics like ayahuasca, psilocybin and lysergic acid diethylamide (LSD) are potential therapeutic options for patients that are not effectively managed by conventional treatment.
• Seven studies were analysed, and found that classical psychedelics produced significant and sustained anti-depressant and anxiolytic effects.
• Psychedelic treatment was well-tolerated with no persisting adverse effects; when occurring, the most common included transnsient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.
• The paucity of data currently available on the subject calls for further research in the field.

Abstract

Background

Depression and anxiety are prevalent psychiatric disorders that carry significant morbidity. Pharmacological and psychosocial interventions are used to manage these conditions, but their efficacy is limited. Recent interest into the use of psychedelic-assisted therapy using ayahuasca, psilocybin or lysergic acid diethylamide (LSD) may be a promising alternative for patients unresponsive to traditional treatments. This review aims to determine the efficacy and tolerability of psychedelics in the management of resistant depression.

Methods

Clinical trials investigating psychedelics in patients with depression and/or anxiety were searched via MEDLINE, EMBASE and PsychINFO. Efficacy was assessed by measuring symptom improvement from baseline, and tolerability was evaluated by noting the incidence and type of adverse effects reported. Risk of bias was assessed.

Results

Seven studies, with 130 patients, were analysed in this review. Three were conducted in patients with depression, two in patients with anxiety and two in patients with both. In a supportive setting, ayahuasca, psilocybin, and LSD consistently produced immediate and significant anti-depressant and anxiolytic effects that were endured for several months. Psychedelics were well-tolerated. The most common adverse effects were transient anxiety, short-lived headaches, nausea and mild increases in heart rate and blood pressure.

Limitations

At present, the number of studies on this subject is very limited; and the number of participating patients within these is also limited as the treatment under investigations is a relatively novel concept.

Conclusions

Though further evidence is required, psychedelics appear to be effective in significantly reducing symptoms of depression and anxiety and are well-tolerated.

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