Background: Ayahuasca is a psychotropic drink made from the Amazonian vine Banisteriopsis caapi. Active components include beta-carboline alkaloids and the hallucinogen N–N-dimethyltryptamine (DMT). This review aimed to identify and summarize the literature on the safety and effectiveness of ayahuasca among recreational users. Method: A comprehensive literature search was done on November 1, 2019 in the following six databases: PubMed(MEDLINE), Ovid Embase, Ovid International Pharmaceutical Abstracts, LILACS, Scopus, and Web of Science. Articles were included if they were original research published in English, Spanish, or Portuguese, among human participants using oral ayahuasca for neuropsychiatric effects. Chemical or pharmacological an­alyses, brain imaging studies, and studies examining the use of ayahuasca within a religious context were excluded. Results: 5750 unique titles were identified through the database searches, with an additional 19 titles identified through manual searches. Ultimately, 39 met all the criteria for inclusion. Articles were organized into 4 themes: (1) Case reports and case series; (2) The use of ayahuasca for depression or grief; (3) The use of ayahuasca and other psychiatric or neuropsychological outcomes; and (4) Studies examining ayahuasca use and physiologic outcomes. Ayahuasca use is associated with a risk of both psychiatric and non-psychiatric events including hallucinations, agitation or aggression, vomiting, seizure, and rhabdomyolysis. Five fatalities have been reported in the literature following ayahuasca use. Open-label studies assessing ayahuasca use in depression found favorable results persisting across 21 days. Ayahuasca was also found to influence the MINDSENS scale for mindfulness, with mixed results observed for impact of ayahuasca on cognitive function and creativity, and benefits observed for measures of self-acceptance and overall wellbeing. Conclusions: To date, evidence on benefits for the management of depression, anxiety, and other mental health disorders is mixed, with some evidence suggesting improvements in mindfulness measures and creativity that are generally short-lived, and multiple case reports suggesting the potential for harm and interactions.