PLoS ONE
August 8, 2012
José Carlos Bouso, Débora González, Sabela Fondevila et al.
313 citations
Regular ayahuasca use over one year is associated with better psychological well-being, mental health, and cognitive performance compared to active controls in non-ayahuasca religions. Users scored higher on Reward Dependence and Self-Transcendence, lower on Harm Avoidance and Self-Directedness, and showed significantly lower psychopathology scores. They performed better on tests of attention, executive function, and working memory (Stroop test, Wisconsin Card Sorting Test, Letter-Number Sequencing). Life attitude measures indicated greater spiritual orientation, purpose in life, and psychosocial well-being. No evidence of psychological maladjustment, mental health deterioration, or cognitive impairment emerged in the ayahuasca group.
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.
Drug and Alcohol Dependence
June 17, 2010
Josep María Fábregas, Débora González, Sabela Fondevila et al.
228 citations
Regular ritual use of ayahuasca, a psychoactive Amazonian tea containing N,N-dimethyltryptamine, does not appear to cause the psychosocial problems typical of other drugs of abuse. In two studies comparing ayahuasca users (56 jungle-based and 71 urban-based) with matched controls, users scored significantly lower on the Addiction Severity Index (ASI) Alcohol Use and Psychiatric Status subscales. Jungle-based users had a higher frequency of past illicit drug use, but this had ceased at examination except for cannabis. At one-year follow-up, abstinence from illicit drugs was maintained except for cannabis in the jungle group. ASI differences remained significant for the jungle group but not the urban group. A time-dependent worsening was observed only in the Family/Social relationships subscale in the urban group.
European Neuropsychopharmacology
January 16, 2015
José Carlos Bouso, Fernanda Palhano-Fontes, Antoni Rodrı́guez-fornells et al.
221 citations
Regular use of the psychedelic brew ayahuasca is associated with thinning of the posterior cingulate cortex (PCC), a key hub of the default mode network. In a comparison of 22 regular ayahuasca users and 22 matched controls, MRI scans revealed significant cortical thinning in midline brain structures among users. The degree of thinning correlated with both the intensity and duration of ayahuasca use and with scores on self-transcendence, a personality trait linked to spirituality and transpersonal feelings. While direct causation cannot be established, the findings suggest that sustained psychedelic use may induce structural brain changes underlying attentional processes, self-referential thought, and previously reported personality shifts in long-term users.
Journal of Psychoactive Drugs
September 1, 2008
José Carlos Bouso, Rick Doblin, Magı́ Farré et al.
206 citations
In a small, prematurely terminated study, six women with chronic posttraumatic stress disorder (PTSD) from sexual assault received low doses (50–75 mg) of MDMA during psychotherapy. The treatment was psychologically and physiologically safe for all participants. The study was originally planned for 29 subjects but closed early due to political pressures. The authors present these preliminary results and call for future research with larger samples and higher doses to better assess MDMA's safety and efficacy for PTSD.
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.
Drug and alcohol dependence
November 8, 2006
Débora González, Jordi Riba, José Carlos Bouso et al.
163 citations
Salvia divinorum, a plant containing the potent kappa-opioid receptor agonist salvinorin-A, is increasingly used recreationally outside its traditional Mazatec context. Among 32 recreational users surveyed, smoking the extract was the preferred method. Effects were intense but short-lived, appearing within one minute and lasting 15 minutes or less. Users reported psychedelic-like changes in visual perception, mood, and bodily sensations, along with a marked alteration in the perception of external reality and self, resulting in impaired ability to interact. While some effects resembled those of classical psychedelics, the intense derealization and impairment appear unique to salvia. High scores on both LSD and PCAG subscales of the ARCI support kappa-opioid receptor activation as the underlying mechanism.
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.
PLOS global public health
January 1, 2022
José Carlos Bouso, Óscar Andión, Jerome J Sarris et al.
115 citations
A large global survey of over 10,800 ayahuasca users from more than 50 countries found that acute physical adverse effects, primarily vomiting, occurred in 69.9% of participants, with 2.3% needing medical attention. Adverse mental health effects in the weeks or months after use were reported by 55.9% of the sample, but about 88% of those viewed these effects as part of a positive growth or integration process; around 12% sought professional support. Physical adverse effects were linked to older age at first use, having a physical health condition, higher lifetime and recent use, a prior substance use disorder diagnosis, and using ayahuasca in unsupervised settings.
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 psychopharmacology (Oxford, England)
July 1, 2012
Fernando Caudevilla-Gálligo, Jordi Riba, Mireia Ventura et al.
99 citations
The psychoactive drug 2C-B, an analogue of mescaline, is increasingly used as a rave and club drug. Analysis of drug samples in Spain showed that the percentage containing 2C-B doubled between 2006 and 2009, shifting from powder to tablet form with low falsification rates. Recreational users typically took about 20 mg orally. Subjective effects included perceptual changes similar to those from ayahuasca and Salvia divinorum, but not from amphetamine or MDMA. Pleasure and sociability were comparable to MDMA, while incapacitation was lower than with the other psychedelics studied. The findings indicate 2C-B is consistently present in Spain's illicit market, producing psychedelic-like perceptual effects but with lower impairment and higher pleasurable effects akin to entactogens.
Drug Testing and Analysis
July 28, 2014
Jordi Riba, Ethan H. Mcilhenny, José Carlos Bouso et al.
96 citations
When N,N-dimethyltryptamine (DMT) is taken orally, it produces no psychedelic effects and no DMT appears in urine, because monoamine oxidase (MAO) breaks it down almost completely into indole-3-acetic acid (97% of recovered compounds). By contrast, smoking DMT yields full psychoactivity, with unmetabolized DMT and DMT-N-oxide rising to 10% and 28% of recovered compounds, while indole-3-acetic acid drops to 63%. An inverse relationship between the ratio of these metabolites and subjective effects indicates that smoking shifts metabolism from efficient MAO-dependent breakdown to less efficient CYP-dependent pathways, enabling psychoactivity.
Psychopharmacology
June 20, 2013
José Carlos Bouso, Josep María Fábregas, Rosa María Antonijoan et al.
96 citations
Acute ayahuasca intake impaired working memory, as measured by increased errors on the Sternberg task, but reduced stimulus-response interference, shown by faster reaction times on the Stroop task with maintained accuracy. Performance on the Tower of London task, which assesses executive function, worsened only in occasional users, not in long-term experienced users. Greater lifetime ayahuasca use was associated with less impairment on the Tower of London. The findings suggest that prior exposure to ayahuasca may protect against acute cognitive disruption, possibly due to compensatory or neuromodulatory effects.
Drug Testing and Analysis
April 19, 2012
Jordi Riba, Ethan H. Mcilhenny, Marta Valle et al.
91 citations
Ayahuasca, an Amazonian tea containing β-carboline alkaloids (harmine, harmaline, tetrahydroharmine) and the psychedelic DMT, is used worldwide, but its metabolism in humans had not been systematically studied. In 10 healthy men given freeze-dried ayahuasca (1.0 mg DMT/kg), less than 1% of DMT was excreted unchanged; about 50% was recovered as indole-3-acetic acid, 10% as DMT-N-oxide, and total DMT plus metabolites reached 68%. Harmala alkaloids were excreted as O-demethylated and conjugated metabolites, but recoveries varied from 9% to 65%. The findings indicate alternative metabolic routes for DMT beyond monoamine-oxidase and that O-demethylation plus conjugation is important but not the only pathway for harmala alkaloids.
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 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.
Front Pharmacol
April 21, 2021
Daniel Perkins, Violeta Schubert, Hana Šimonová et al.
73 citations
A large international survey of ayahuasca drinkers found that the context and setting in which ayahuasca is consumed—including preparation, guidance, and integration support—are strongly associated with mental health and wellbeing outcomes. Participants who reported professional or traditional guidance, structured preparation, and post-session integration were more likely to experience improvements in mood, reductions in anxiety, and overall psychological wellbeing. The findings suggest that the benefits of ayahuasca are not solely due to the substance itself but are significantly influenced by the surrounding environmental and support factors. Negative or null outcomes were more common among those who lacked such structured support.
Psychopharmacology
January 14, 2020
Débora González, Jordi Cantillo, Irene Hidalgo Pérez et al.
73 citations
In a bereaved sample attending Shipibo ayahuasca ceremonies in Peru, grief severity decreased substantially from baseline to 12 months, with large effect sizes (Cohen's d = 0.84 at 15 days, 1.38 at 3 months, 1.16 at 6 months, and 1.39 at 12 months). Reductions in grief were linked to lower experiential avoidance (r = 0.55) and greater decentering (r = -0.47). The ceremonial use of ayahuasca appears to have therapeutic value for grief, with acceptance and decentering as mediating psychological processes.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
Neuroscience & Biobehavioral Reviews
October 5, 2020
Genís Ona, José Carlos Bouso
59 citations
Microdosing psychedelic drugs like LSD or psilocybin is increasingly common in Western societies, primarily for enhancing mood or creativity. This systematic review of human studies examined efficacy, safety, and the role of placebo effects. The evidence shows strengths such as large sample sizes and robust methods, but also limitations like gender bias and inconsistent dosing. Results are highly contradictory, with some studies reporting benefits and others reporting detriments to mood, creativity, and energy. The review offers an overview of methods to guide future research.
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.
Psychiatry Research
April 4, 2018
Alba Franquesa, Alberto Sainz-Cort, Sam Gandy et al.
58 citations
Ayahuasca, a psychedelic brew from Amazonia, may support mental health and boost mindfulness, but the psychological mechanisms behind its therapeutic effects are unclear. Comparing 81 ayahuasca users with 41 non-users, users scored higher on Decentering and Positive self, but not on Valued living, Life fulfillment, or measures of self in social or close relations. More experienced users (over 15 sessions) showed higher Decentering scores than less experienced ones. These findings suggest that psychological processes like Decentering could help explain ayahuasca's benefits in psychotherapy, warranting their inclusion in future studies.