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.
Expert Review of Clinical Pharmacology
August 13, 2018
Rafael G. Dos Santos, José Carlos Bouso, Miguel Ángel Alcázar‐córcoles et al.
231 citations
Serotonergic hallucinogens/psychedelics such as ayahuasca, psilocybin, and LSD show promise for reducing anxiety, depression, and substance dependence. Psilocybin and LSD reduced anxiety and depression in cancer patients and symptoms of alcohol and tobacco dependence; ayahuasca reduced depression symptoms in treatment-resistant depression. However, many studies were open-label, few were randomized controlled trials, most had small sample sizes and short duration. Single or few doses appear well tolerated, but long-term studies are lacking. New RCTs with larger samples and longer duration are needed to confirm these findings.
Journal of Ethnopharmacology
April 26, 2007
Rafael G. Dos Santos, J. Landeira-Fernández, Rick J. Strassman et al.
206 citations
Ayahuasca, a hallucinogenic brew made from Banisteriopsis caapi and Psychotria viridis, is increasingly used in urban centers, yet its emotional effects are not well understood. In a double-blind, placebo-controlled study conducted in a Santo Daime church, long-term members who had ingested ayahuasca for at least 10 consecutive years completed questionnaires one hour after consumption. Under the acute effects, participants scored lower on measures of panic and hopelessness, while state- and trait-anxiety remained unchanged. The findings suggest ayahuasca may help alleviate hopelessness and panic-like symptoms.
Therapeutic Advances in Psychopharmacology
February 23, 2017
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
167 citations
Ayahuasca, a hallucinogenic brew from the Northwestern Amazon, contains DMT, which acts on serotonin 5-HT2A receptors similarly to LSD and psilocybin. Controlled use of these substances is rarely linked to psychotic episodes, but little is known about use outside controlled settings. A systematic review of case reports identified three case series and two case reports of psychotic episodes after ayahuasca use, and three case reports after DMT use. Many cases involved individuals with personal or family histories of psychosis or other drug use, though some episodes occurred in people without such histories. Overall, psychotic episodes appear rare in both ritual and recreational settings. Psychiatric screening before hallucinogen administration in controlled settings may reduce adverse reactions; individuals with personal or family histories of psychotic illness or mania should avoid hallucinogens.
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.
Psychopharmacology
August 12, 2011
Rafael G. Dos Santos, Eva Grasa, Marta Valle et al.
139 citations
The human pharmacology of ayahuasca, an Amazonian tea containing the psychedelic DMT, was evaluated after repeated doses. In a double-blind, crossover, placebo-controlled trial, nine experienced psychedelic drug users received either a placebo followed by ayahuasca, or two ayahuasca doses four hours apart. DMT plasma concentrations, subjective and neurophysiological effects, and serum prolactin and cortisol were higher after two doses. When effects were adjusted for plasma DMT, no differences appeared for subjective, neurophysiological, autonomic, or immunological measures. A trend toward reduced systolic blood pressure and heart rate, and significant tolerance to growth hormone secretion, were observed after the second dose. No clear tolerance or sensitization occurred in psychological or most physiological variables.
Journal of Clinical Psychopharmacology
October 15, 2011
Rafael G. Dos Santos, Marta Valle, José Carlos Bouso et al.
136 citations
Ayahuasca, an Amazonian psychotropic tea containing DMT and β-carboline alkaloids, produced moderate sympathomimetic effects, significant increases in prolactin and cortisol, and time-dependent changes in immune cell populations in a double-blind crossover trial with 10 healthy volunteers. Pupil dilation occurred with both ayahuasca and amphetamine, but ayahuasca’s effects were milder. Prolactin rose only after ayahuasca, while cortisol peaked higher with ayahuasca than with amphetamine. Lymphocyte subsets shifted similarly for both drugs: CD4 and CD3 percentages decreased, and natural killer cells increased, with maximum changes at 2 hours and return to baseline by 24 hours.
Neuroscience & Biobehavioral Reviews
February 13, 2018
José Carlos Bouso, Rafael G. Dos Santos, Miguel Ángel Alcázar‐córcoles et al.
135 citations
Serotonergic psychedelics, which activate 5-HT2A receptors in the brain, can alter personality traits. A systematic review of 18 studies from 1985 to 2016 found that traits like Absorption and Self-Transcendence influence how people respond to these drugs. Users and nonusers differ in certain personality characteristics. When given in controlled settings, psychedelics may increase Openness and Self-Transcendence. Acute administration raises global brain entropy, which predicts changes in Openness. In long-term ayahuasca users, Self-Transcendence is negatively correlated with thinning of the posterior cingulate cortex. Both acute and long-term use appear to produce personality changes mediated by 5-HT2A receptors, suggesting therapeutic potential that warrants further randomized controlled trials.
Journal of Psychopharmacology
June 11, 2016
Rafael G. Dos Santos, Fermanda M Balthazar, José Carlos Bouso et al.
126 citations
A systematic review of 28 human studies found that acute ayahuasca administration is well tolerated, increases introspection and positive mood, alters visual perceptions, activates frontal and paralimbic brain regions, and decreases default mode network activity. It improves planning and inhibitory control but impairs working memory, and shows antidepressive and antiaddictive potentials. Long-term use is associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, inversely correlated to age of onset, intensity of prior use, and spirituality. Subacute and long-term use is not linked to increased psychopathology or cognitive deficits but to enhanced mood, cognition, spirituality, and reduced impulsivity. Overall toxicity appears low, though therapeutic effects need replication.
Scientific Reports
March 5, 2020
José Carlos Bouso, Daniel Jiménez‐garrido, María de Lourdes Gómez-sousa et al.
111 citations
Ayahuasca, a hallucinogenic decoction used in traditional Amazonian medicine, may have therapeutic benefits for psychiatric disorders. In a study of 40 first-time users, nearly half (45%) initially met criteria for a psychiatric disorder; after ayahuasca use, more than 80% of those showed clinical improvements that persisted at 6 months. Questionnaires indicated significant reductions in depression and psychopathology. Long-term users (n=23) had lower depression scores and higher self-transcendence and quality of life compared to first-time users. The authors suggest further controlled and observational studies are warranted to assess risks and benefits.
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.
Psychopharmacology
February 1, 2021
Richard J. Zeifman, Nikhita Singhal, Rafael G. Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
Scientific Reports
November 3, 2017
Will Lawn, Jaime E. C. Hallak, José Alexandre S. Crippa et al.
78 citations
Ayahuasca users reported greater well-being than both classic psychedelic users and non-psychedelic drug users, and less problematic drinking than classic psychedelic users, though both psychedelic groups reported more problematic drinking than non-psychedelic users. Ayahuasca's acute subjective effects typically lasted six hours, peaking one hour after consumption. These findings come from a large online survey of nearly 97,000 respondents, including 527 ayahuasca users. The authors call for longitudinal studies and randomized trials to further investigate ayahuasca's effects on well-being and alcohol use.
Journal of Psychoactive Drugs
February 7, 2019
Genís Ona, Maja Kohek, Tomàs Massaguer et al.
76 citations
Long-term ayahuasca use in community settings is linked to better self-reported health and healthier lifestyles. A survey of 380 regular users in Spain found that 56% reduced their prescription drug use after starting ayahuasca. Those who had used ayahuasca more than 100 times scored higher on measures of personal values. The authors conclude that respectful, controlled use of psychedelic drugs in group settings can benefit public health.
Journal of Psychoactive Drugs
December 5, 2016
Rafael G. Dos Santos, Jaime E. C. Hallak
64 citations
Harmine, a natural alkaloid found in ayahuasca and Syrian rue, shows neuroprotective and cognitive-enhancing effects in preclinical studies. A systematic review of two hippocampal cell culture studies and nine animal model studies found that harmine reduced excitotoxicity, inflammation, and oxidative stress, increased brain-derived neurotrophic factor levels, and improved memory and learning. These effects may involve monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreased reactive oxygen species, increased neurotrophic factors, and anti-inflammatory actions. Further preclinical and human research is needed.
Risk Management and Healthcare Policy
March 1, 2021
Rafael G. Dos Santos, José Carlos Bouso, Juliana Mendes Rocha et al.
58 citations
Psychedelics such as LSD, psilocybin, and ayahuasca act mainly by stimulating serotonin 5-HT2A receptors, producing changes in perception, cognition, and mood. Although used ritually for centuries, they now show promise for rapid and lasting antidepressant, anxiolytic, and anti-addictive effects after single or few doses, especially in patients resistant to standard treatments. However, their legal status as scheduled substances and social stigma, particularly for LSD and psilocybin, hinder clinical trials and access, potentially violating human rights. Ayahuasca rituals face less public criticism. Integrating these therapies into health systems requires rigorous evidence, respect for traditional use, and dialogue among science, society, and policy.
Epilepsy & Behavior
June 7, 2019
Rafael G. Dos Santos, Jaime E. C. Hallak
58 citations
Ayahuasca, a botanical hallucinogenic preparation traditionally used for ritual and therapeutic purposes by native populations of the Northwestern Amazon, has spread globally in recent decades, increasing interest in its potential therapeutic uses for anxiety, mood disorders, and substance-use disorders. Preclinical, observational, and preliminary clinical studies have corroborated some therapeutic findings. This article provides an overview of these studies and highlights current uses of ayahuasca in neuroscience, including as a tool to investigate the neural basis of introspection and other complex cognitive processes.
Journal of Psychopharmacology
March 19, 2021
Rafael G. Dos Santos, Jaime Ec Hallak, Glen B. Baker et al.
51 citations
Major depressive disorder affects many people worldwide and current antidepressants often work slowly, have side effects, and fail about a third of patients. Psychedelics such as LSD, psilocybin, and ayahuasca are among the few compounds with recent human evidence of fast-acting antidepressant effects. Studies from the 1950s to 1970s reported antidepressive and anxiolytic effects, which modern trials are confirming (LSD, one trial; psilocybin, five trials; ayahuasca, two trials). These drugs appear to work primarily by activating serotonin receptors, especially the 5-HT2A receptor. The promising but limited evidence of safety and efficacy has encouraged further research into psychedelics for depression.
Brazilian Journal of Psychiatry
October 30, 2020
Ícaro Durante, Rafael G. Dos Santos, José Carlos Bouso et al.
49 citations
A small fraction of participants experienced lasting negative effects from ayahuasca use. Taking psychiatric medication during ayahuasca ceremonies did not raise the risk of adverse effects. The safety practices of the institution appear adequate to prevent severe reactions. Future research should investigate those who are negatively affected.
European Archives of Psychiatry and Clinical Neuroscience
June 1, 2022
Lucas Silva Rodrigues, Giordano Novak Rossi, Juliana Mendes Rocha et al.
48 citations
Ayahuasca and its alkaloids show therapeutic potential for substance use disorders, according to an updated systematic review of nine studies (four preclinical, five observational) published between 2016 and 2020. Preclinical rodent studies found reductions in amphetamine self-administration, anxiety, and conditioned place preference for alcohol and methylphenidate. Observational studies in healthy ritual ayahuasca users and patients with substance use disorders reported decreased drug use, anxiety, and depression, along with improved quality of life and well-being. The review replicates earlier findings but notes limited translation from animal studies, inability to infer causality from observational designs, and lack of dose standardization. Randomized controlled trials are needed.
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.