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
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa, Jordi Riba, Antônio Waldo Zuardi, Jaime E. C. Hallak
Therapeutic Advances in Psychopharmacology March 18, 2016 DOI: 10.1177/2045125316638008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Placebo-controlled Double-blind Open-label Peer reviewed |
|---|---|
| Population | Patients from included clinical trials |
| Interventions | Ayahuasca Psilocybin Lysergic acid diethylamide |
| Topics | Anxiety Ayahuasca LSD Psilocybin |
| Keywords | Hallucinogen Mood Anxiolytic Clinical trial Clinical psychology Pharmacology |
| Citations | 306 |
| Key findings | Ayahuasca, psilocybin, and LSD may have beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence, but all reviewed studies had small sample sizes and many were open-label. |
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.
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Ayahuasca, psilocybin, and LSD may have beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence, but all reviewed studies had small sample sizes and many were open-label.
Synthesized
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Reviewed clinical trials suggest beneficial effects of ayahuasca, psilocybin, and LSD for anxiety and depression associated with life-threatening diseases, though all studies had small sample sizes and half were open-label.
Synthesized
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Reviewed clinical trials suggest beneficial effects of ayahuasca, psilocybin, and LSD for treatment-resistant depression and anxiety/depression associated with life-threatening diseases, but all studies had small samples and half were open-label.
Synthesized
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State of the evidence: Ayahuasca Supports
The systematic review suggests that ayahuasca, psilocybin, and LSD may have beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence, but all reviewed studies had small sample sizes and many were open-label.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on ayahuasca for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| [Efficacy of psychedelics in psychiatry, a systematic review of the literature]. Patients with psychiatric conditions (anxiety, depression, major depressive disorder,... | 2021 | Systematic review | n = 25 |
| The current state of ayahuasca research in animal models: A systematic review. Rodents, primates, and zebrafish | 2023 | Systematic review | n = 32 |
| Preliminary effects of ayahuasca on mental and physical health: A systematic review of prospective studies Unselected volunteers attending ayahuasca retreat centers | 2026 | Systematic review | n = 18 |
| Ayahuasca, etnofarmacologia e usos no tratamento do transtorno de ansiedade: uma revisão sistemática | 2024 | Systematic review | |
| Rapid and prolonged antidepressant and antianxiety effects of psilocybin, lysergic acid diethylamide, ayahuasca, and 3, 4-methylenedioxy-methamphetamine. A systematic review and meta-analysis of randomized controlled trials | 2024 | Systematic review and meta-analysis |