title: 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.
authors.affiliation: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Hospital das Clínicas, Terceiro Andar, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Dos Santos
authors.affiliation: Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, SP, Brazil National Institute for Translational Medicine (INCT-TM), CNPq, Brazil.
authors.forename: Flávia L
authors.initials: FL
authors.lastname: Osório
authors.affiliation: Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, SP, Brazil National Institute for Translational Medicine (INCT-TM), CNPq, Brazil.
authors.forename: José Alexandre S
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
authors.affiliation: Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, SP, Brazil National Institute for Translational Medicine (INCT-TM), CNPq, Brazil.
authors.forename: Antônio W
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, SP, Brazil National Institute for Translational Medicine (INCT-TM), CNPq, Brazil.
authors.forename: Jaime E C
authors.initials: JE
authors.lastname: Hallak
keywords: LSD; ayahuasca; dimethyltryptamine; hallucinogens; psilocybin; tryptamines