Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
Brazilian Journal of Psychiatry
March 1, 2015
Flávia de Lima Osório, Rafael Faria Sanches, Ligia Ribeiro Horta de Macedo et al.
486 citations
A single dose of ayahuasca produces fast-acting reductions in anxiety and depression symptoms in people diagnosed with a depressive disorder.
Journal of Clinical Psychopharmacology
December 11, 2015
Rafael Faria Sanches, Flávia de Lima Osório, Rafael G. Dos Santos et al.
468 citations
A single oral dose of ayahuasca, an Amazonian brew containing dimethyltryptamine and harmine, produced fast-acting and sustained reductions in depression severity among 17 patients with recurrent depression. Scores on the Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, and Brief Psychiatric Rating Scale decreased significantly from 80 minutes through 21 days after intake. Brain imaging showed increased blood flow in the left nucleus accumbens, right insula, and left subgenual area—regions involved in mood regulation. Vomiting occurred in 47% of participants, but no other adverse effects were reported. The authors suggest ayahuasca may have antidepressant properties but call for replication in randomized, double-blind, placebo-controlled trials.
Therapeutic Advances in Psychopharmacology
March 18, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
306 citations
A systematic review of clinical trials from 1990 to 2015 examined the therapeutic potential of ayahuasca, psilocybin, and LSD for mood and anxiety disorders and drug dependence. Six trials met inclusion criteria. The 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. However, all studies had small sample sizes, and half were open-label, proof-of-concept studies. The authors conclude these substances may be useful pharmacological tools, but randomized, double-blind, placebo-controlled studies with more patients are needed to replicate preliminary findings.
Brazilian Journal of Psychiatry
March 1, 2016
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
158 citations
Ayahuasca and its alkaloids show promise as potential treatments for anxiety and depression, offering a possible alternative to current drugs that often have adverse effects. The abstract calls for further investigation into these compounds to develop more effective and safer therapies.
Journal of Psychoactive Drugs
May 26, 2016
Amanda Amorin Nunes, Rafael G. Dos Santos, Flávia de Lima Osório et al.
92 citations
Ayahuasca, a hallucinogenic beverage containing DMT and β-carbolines, shows potential for treating addiction. A systematic review of five animal studies and five observational human studies found that ayahuasca or its components improved biochemical or behavioral measures related to drug-induced disorders. Four of five human studies reported significant reductions in dependence symptoms or substance use; one found no significant effect. The anti-addictive mechanisms are unclear but may involve peripheral MAO-A inhibition by β-carbolines and central 5-HT2A receptor activation by DMT in brain regions regulating mood. Controlled studies are needed to confirm these preliminary findings.
Journal of Clinical Psychopharmacology
June 23, 2021
Rafael G. Dos Santos, Flávia de Lima Osório, Juliana Mendes Rocha et al.
85 citations
Ayahuasca, a classic hallucinogen with anxiolytic and antidepressive properties, improved self-perception of speech performance in individuals with social anxiety disorder. In a pilot, proof-of-concept, randomized, parallel-group trial with 17 volunteers, ayahuasca significantly increased positive self-statements during a public-speaking test compared with placebo, alongside increased somatic symptoms such as nausea and gastrointestinal discomfort. The drug did not significantly alter task-related anxiety or recognition of emotions in facial expressions, suggesting a specific cognitive effect on speech performance. Ayahuasca was well tolerated overall, and further research is needed to understand the mechanisms involved.
Journal of Clinical Psychopharmacology
April 13, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
46 citations
A single dose of ayahuasca did not alter the recognition of emotions in facial expressions compared with placebo in healthy volunteers. The drug was well tolerated, producing nausea, gastrointestinal discomfort, and vomiting, with some reports of visual effects, tranquility, and well-being, and few reports of transient anxiety or confusion. No significant effects appeared on cardiovascular measures or brain-derived neurotrophic factor levels. A significant time-dependent deterioration of alkaloids, especially dimethyltryptamine, was observed. The absence of effects on emotion recognition may stem from the dose used, alkaloid degradation, learning effects, or the sample's high educational level.
Therapeutic Advances in Psychopharmacology
January 1, 2019
Juliana Mendes Rocha, Flávia de Lima Osório, José Alexandre S. Crippa et al.
44 citations
A systematic review of 8 studies found that serotonergic hallucinogens such as LSD and psilocybin reduce the recognition of negative emotions in facial expressions and modulate amygdala activity in response to these stimuli. These effects correlated with antidepressive benefits in patients. The drugs were well tolerated. Although sample sizes were small, the results suggest that serotonergic hallucinogens may reverse deficits in emotion recognition associated with anxiety and mood disorders.
Frontiers in Psychiatry
August 6, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
37 citations
In two small randomized placebo-controlled trials, ayahuasca did not consistently change personality traits. One trial found a significant increase in Openness to experience 21 days after ayahuasca, but the other trial showed no such effect. Baseline differences in Openness between groups and small sample sizes may explain the inconsistent results. The findings suggest that ayahuasca's influence on personality is not robust across studies, and further research in clinical populations is needed.
Archives of Clinical Psychiatry (São Paulo)
February 1, 2018
Rafael G. Dos Santos, Rafael Faria Sanches, Flávia de Lima Osório et al.
37 citations
Ayahuasca, a botanical hallucinogenic preparation containing β-carboline alkaloids and DMT, was well tolerated by patients with treatment-resistant major depressive disorder in an open-label trial. Symptom reductions lasted only a few weeks, but most patients considered the experience among the most important of their lives, even 4 to 7 years later. This is the first long-term follow-up of a clinical sample from an ayahuasca trial, suggesting that while acute antidepressant effects are short-lived, the subjective significance endures.
bioRxiv (Cold Spring Harbor Laboratory)
January 27, 2017
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
22 citations
preprint
A single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
Human Psychopharmacology Clinical and Experimental
February 2, 2022
Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi et al.
20 citations
A post-hoc analysis of two small randomized placebo-controlled trials measured endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.
Journal of Psychedelic Studies
April 1, 2017
Rafael G. Dos Santos, Flávia de Lima Osório, José Alexandre S. Crippa et al.
7 citations
Ayahuasca, a hallucinogenic beverage containing dimethyltryptamine and β-carbolines, is traditionally used by Indigenous groups in the Northwest Amazon for ritual and healing. While animal and human studies suggest it has antidepressant and anxiolytic effects and a good safety profile, anxiety-like reactions can occur, though rarely. This case report describes a symptom-free young woman with generalized anxiety disorder who experienced intense anxiety, panic, and hopelessness during and for three days after an ayahuasca ritual. Symptoms began within hours, gradually reduced over days, but were severe enough to require psychiatric help and restarting medication. This is the first reported subacute or prolonged anxiety-like reaction to ayahuasca, indicating it should be used cautiously in people with a history of anxiety disorders.
Psychoactives
November 17, 2023
Anna Beatriz Vicentini, Lucas Silva Rodrigues, Giordano Novak Rossi et al.
4 citations
In a single-blind study, university students aged 18 to 24 with harmful alcohol use received one dose of ayahuasca (1 mL/kg). Twenty-one days later, semi-structured interviews with six participants identified psychological elements linked to reduced drinking. Content analysis revealed categories including Positive Impacts, Substance Use Pattern, and Insights. Together, these categories suggest that insights and positive emotions from the experience may foster internal transformation, potentially leading to decreased alcohol consumption.