Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years

Abstract

To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.

In the evidence

This study is part of the evidence base for 4 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Ayahuasca for anxiety ↑Supports

  Reviewed trials suggest ayahuasca, psilocybin, and LSD may benefit anxiety and depression associated with life-threatening illness and treatment-resistant depression, but all studies had small samples and half were open-label.

  Synthesized October 22, 2026

• State of the evidence: LSD for anxiety ↑Supports

  Reviewed trials suggested beneficial effects of these psychedelics on anxiety and depression associated with life-threatening diseases, but all had small samples and half were open-label.

  Synthesized October 22, 2026

• State of the evidence: Psilocybin for anxiety ↑Supports

  Reviewed trials suggest beneficial effects of ayahuasca, psilocybin, and LSD for anxiety and depression associated with life-threatening illness and treatment-resistant depression, but all had small samples and half were open-label.

  Synthesized October 22, 2026

• State of the evidence: Ayahuasca ↑Supports

  Reviewed trials suggest beneficial effects of ayahuasca, psilocybin, and LSD for treatment-resistant depression, anxiety and depression in life-threatening illness, and tobacco and alcohol dependence, though all studies had small samples and half were open-label.

  Synthesized October 19, 2026

Comparable studies

Other systematic reviews and meta-analyses on ayahuasca for anxiety, most cited first.