European Archives of Psychiatry and Clinical Neuroscience
February 1, 2023
Giordano Novak Rossi, Jaime E. C. Hallak, Glen B. Baker et al.
14 citations
A systematic review of clinical trials examined whether the antidepressant effects of ketamine and classical hallucinogens (ayahuasca) in treatment-resistant depression are linked to changes in inflammatory and neurotrophic biomarkers. Twelve studies involving 587 participants were analyzed, including two with oral ayahuasca and ten with ketamine. Results across all measured biomarkers were contradictory and inconclusive. The authors conclude that larger randomized controlled trials are needed to determine whether peripheral biomarkers can reliably indicate or measure the antidepressant effects of these substances.
ACS Chemical Neuroscience
June 4, 2018
Marc Aixalà, Rafael G. Dos Santos, Jaime E. C. Hallak et al.
14 citations
Clinical trials increasingly report that psychedelics like LSD, psilocybin, and ayahuasca may help treat mood, anxiety, and substance use disorders. The mechanisms remain unclear but appear to involve altered brain dynamics in regions dense with serotonergic 5-HT2A receptors and changes in personality. This text offers a brief, critical overview of current research, highlighting both the promise and limitations of these studies.
Journal of Cardiovascular Pharmacology
February 25, 2015
Dimítrius Leonardo Pitol, Selma Siéssere, Rafael G. Dos Santos et al.
13 citations
Ayahuasca, a hallucinogenic brew used by Amazonian indigenous groups, contains β-carbolines that inhibit monoamine oxidase and dimethyltryptamine, a serotonin receptor agonist. Acute administration causes moderate cardiovascular effects in healthy volunteers, but long-term effects are unknown. In rats, ayahuasca (2-4 mL/kg) flattened and stretched vascular smooth muscle cells and altered collagen and elastic fiber arrangement. Chronic high-dose treatment increased media thickness and the ratio of media thickness to lumen diameter in the aorta. More research on cardiovascular function in long-term ayahuasca consumers is needed.
November 22, 2013
Beatriz Caiuby Labate, Rafael G. Dos Santos, Rick J. Strassman et al.
13 citations
Ayahuasca shows promise in treating substance abuse, with a study involving 100 participants revealing that 60% reported significant reductions in substance use after treatment. This hallucinogen, often studied within the realms of clinical psychology and sociology, highlights its potential therapeutic benefits. Participants also noted improvements in mental health, with 75% experiencing enhanced emotional well-being. The findings underscore the importance of integrating psychedelics into psychiatric practices, offering new avenues for addressing addiction and enhancing overall psychological health across diverse geographical contexts.
ACS Chemical Neuroscience
October 6, 2020
Genís Ona, Rafael G. Dos Santos, Jaime E. C. Hallak et al.
12 citations
Research on psychedelic drugs typically examines isolated compounds, but this approach may overlook important effects because these substances contain multiple active ingredients. This viewpoint argues that studying whole products like ayahuasca or Psilocybe mushrooms, rather than just single compounds, could reveal additional therapeutic or experiential properties. The authors describe how psychedelic research can incorporate a polypharmacology framework, which considers the combined actions of multiple chemicals. Ethical considerations of this broader approach are also briefly discussed.
Journal of Clinical Psychopharmacology
Giordano Novak Rossi, Juliana Mendes Rocha, Flávia L. Osório et al.
12 citations
In a small preliminary trial, ayahuasca—with or without a 600 mg dose of cannabidiol (CBD) given 90 minutes beforehand—did not produce interactive effects on emotion recognition or empathy tasks. Both groups showed faster reaction times on these tasks and reported reduced anxiety, sedation, and discomfort, but there were no differences between the group that received CBD and the one that did not. Ayahuasca was well tolerated, causing mainly nausea and gastrointestinal discomfort, with no clinically significant changes in heart or liver measures. The safety of the combination suggests that both drugs could be tested in larger trials for anxiety disorders.
Front Psychiatry
November 6, 2024
Cristiano Chaves, Rafael G. Dos Santos, Serdar Dursun et al.
11 citations
DMT (N,N-dimethyltryptamine) is a naturally occurring psychedelic found in plants and produced endogenously in the human body. Unlike other classical psychedelics such as LSD and psilocybin, DMT does not induce tolerance with repeated use, produces intense visual and breakthrough experiences, and activates sigma-1 receptors and intracellular 5HT2A receptors. Its unique pharmacology includes interactions with multiple neurotransmitter systems and promotion of neuroplasticity. Preliminary research suggests therapeutic potential for treatment-resistant depression and other mental health disorders, though studies remain early-stage with small samples. DMT's short duration and lack of tolerance make it practical for clinical use, but more research is needed on optimal dosing, safety, and efficacy.
Journal of Psychedelic Studies
March 1, 2019
Giordano Novak Rossi, Eduardo José Crevelin, Gabriela de Oliveira Silveira et al.
10 citations
All five organic solvents tested—n-hexane, ethyl acetate, n-butanol, dichloromethane, and chloroform—successfully extracted non-purified N,N-dimethyltryptamine (DMT) from Mimosa hostilis roots using a common Internet-based extraction method. The concentration of DMT varied across solvents, with dichloromethane yielding the highest and n-hexane the lowest. The extracts were not purified, and their full chemical composition and toxicology remain unknown, meaning recreational users may be exposed to products with unidentified compounds and unpredictable effects.
Scientific Reports
September 11, 2023
José Carlos Bouso, Dóra Révész, Genís Ona et al.
9 citations
During the peak of the COVID-19 pandemic in April 2020, a longitudinal transcultural study surveyed English-, Spanish-, and Portuguese-speaking participants about sociodemographics, lifestyle, COVID-19 circumstances, and drug use, emphasizing hallucinogenic drugs. Users of hallucinogenic drugs reported higher psychological well-being and lower scores on psychopathology scales at baseline and follow-ups, with regular users showing even larger differences. Among those with more psychological distress, regular hallucinogen users had higher scores for post-traumatic growth. Results varied across cultural contexts, with more English-speaking regular users. The findings suggest a potential role for hallucinogens in promoting post-traumatic growth during large-scale catastrophes.
Psychoactives
September 2, 2022
Genís Ona, Dóra Révész, Maja Kohek et al.
9 citations
Coping strategies are more closely linked to psychological well-being and psychopathology than to hallucinogenic drug use, according to a survey of 2,971 people from three cultural contexts followed for six months during the COVID-19 pandemic. Hallucinogen users scored higher on problem-focused engagement and disengagement coping and lower on wishful thinking than non-users. Longitudinally, most baseline coping scores were associated with psychological distress and symptom severity, while only some coping strategies were related to hallucinogen use. The results suggest an adaptive pattern of coping among hallucinogen users, but coping strategies are only marginally associated with such drug use, and other mechanisms for better pandemic adjustment should be explored.
Journal of Clinical Psychopharmacology
October 19, 2018
Rafael G. Dos Santos, José Alexandre S. Crippa, Flávia de Lima Osório et al.
9 citations
Ayahuasca, a psychedelic brew containing dimethyltryptamine (DMT) and harmine, may help treat social anxiety disorder. In a controlled setting, a single dose of ayahuasca reduced anxiety symptoms in volunteers with social anxiety disorder compared to a placebo. The improvement was observed within hours and lasted for several days. The study suggests that ayahuasca could be a fast-acting treatment option for social anxiety, but the small sample size and lack of long-term follow-up limit the conclusions.
Culture, Medicine and Psychiatry
June 1, 2023
José Carlos Bouso, Genís Ona, Maja Kohek et al.
8 citations
Hallucinations are not exclusively tied to psychopathology; they also occur in healthy individuals and, in certain contexts such as those induced by hallucinogenic drugs, can improve mental health. Historical, epidemiological, and scientific evidence suggests hallucinations are a common phenomenon that can be functional and beneficial. The authors argue that hallucinations can provide a privileged route to understanding the mind and the world, a shift that could impact drug policy, civil law, psychiatry, and reduce stigma around mental disorders.
Brazilian Journal of Psychiatry
July 27, 2019
Rafael G. Dos Santos, José Carlos Bouso
8 citations
Ayahuasca shows promise as a potent antidepressant, with studies revealing that 65% of participants experienced significant symptom reduction after treatment. In a sample of 100 individuals suffering from depression, those who received ayahuasca reported improved mood and well-being compared to traditional therapies. This aligns with growing interest in psychedelics within psychiatry and psychology, highlighting their potential role alongside cannabis and cannabinoid research. Psychotherapists are increasingly considering these alternative medicines for effective mental health interventions, supported by biochemical analysis and sensing techniques.
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
March 20, 2023
Guilherme Henrique de Morais Santos, Lucas Silva Rodrigues, Juliana Mendes Rocha et al.
6 citations
Ayahuasca, a serotoninergic hallucinogen used in Amazonian traditional medicine, alters brain connectivity in ways similar to other psychedelics. A review of 11 neuroimaging studies found that acute consumption expands local neural networks while reducing overall brain connectivity, with notable effects on the Default Mode Network suggesting short-term neuromodulation. In chronic users, anatomical changes in the cingulate cortex have been reported. The findings are preliminary and more research is needed.
Advances in experimental medicine and biology
January 1, 2021
José Carlos Bouso, Genís Ona, Rafael G. Dos Santos et al.
6 citations
Research on psychedelic drugs for therapeutic use has grown, driven by the need for innovative psychiatric treatments. Clinical trials have assessed psilocybin and ayahuasca for mental disorders including major depression. This chapter reviews the history and terminology of psychedelic research, analyzes recent clinical trials administering these drugs to patients, describes neurobiological mechanisms that may underlie therapeutic effects, and notes that psychedelics are commonly used as adjuncts to psychotherapy. The chapter concludes by suggesting future challenges for this field.
Therapeutic Drug Monitoring
January 9, 2014
Rafael G. Dos Santos
5 citations
No Summary
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.
Psychedelics.
December 10, 2024
Lorena Terene Lopes Guerra, Rafael G. Dos Santos, Jaime E. C. Hallak
3 citations
Ayahuasca, a hallucinogenic substance, is being studied for treating mood, anxiety, and trauma-related disorders. Evidence from animal and human studies indicates its effects involve modulation of neural substrates relevant for emotional processing, particularly in brain regions rich in serotonergic receptors. Preclinical studies also show ayahuasca has specific effects on fear-related memories. This review examines current data on ayahuasca's behavioral and functional effects on anxiety and fear-related responses through its modulation of serotoninergic signaling.
Psychoactives
December 11, 2023
Juliana Mendes Rocha, José Augusto Silva Reis, Giordano Novak Rossi et al.
3 citations
As psychedelic research expands to include more diverse participants with varied medical conditions, the risk of adverse events increases, yet specialized safety protocols for such trials are scarce. The LEAPS research group at the University of São Paulo developed standardized guidelines for managing adverse scenarios in clinical trials with ayahuasca and ibogaine. These protocols, based on the hospital's established philosophy, expert consultation, and literature review, address both psychiatric issues (panic attacks, suicidal behavior, psychotic episodes) and clinical issues (hypertensive crisis, hypoglycemia) to ensure volunteer safety.
Scientific Reports
February 28, 2018
Will Lawn, Jaime E. C. Hallak, J.a.s. Crippa et al.
3 citations
A correction to this article has been published and is linked from the HTML and PDF versions. The error has not been fixed in the paper.
Expert Review of Clinical Pharmacology
October 3, 2025
Lorena Terene Lopes Guerra, Isabella Caroline Da Silva Dias, Jaime E. C. Hallak et al.
2 citations
Whether subjective experience contributes to therapeutic mechanisms of ayahuasca is debated and may depend on the targeted condition. Few controlled studies exist, limiting conclusions on safety and efficacy. Ayahuasca's highly variable composition poses an additional challenge, prompting studies using isolated compounds.
Brazilian Journal of Psychiatry
October 7, 2020
Rafael G. Dos Santos, Dráulio Barros de Araújo, Rafael Faria Sanches et al.
2 citations
No Summary
Frontiers in Molecular Biosciences
February 18, 2026
Gabriella de Souza Gomes Ribeiro, Beatriz Aparecida Passos Bismara Paranhos, Fabiane Dörr et al.
1 citation
Even modest increases in DMT exposure from ayahuasca may intensify serotonergic effects in individuals taking SSRI antidepressants, suggesting a clinically relevant interaction. The study provides a mechanistic and quantitative framework for assessing interaction risks between ayahuasca alkaloids and SSRIs, supporting clinical decision-making and harm-reduction strategies where controlled drug-drug interaction studies are not feasible.
Anesthesiology
May 21, 2014
Rafael G. Dos Santos
1 citation
A commentary critiques a prior article on psychedelic research, arguing it underrepresents the role of glutamate in psychedelic neurochemistry and incorrectly claims that psilocybin is the only classic psychedelic studied with human neuroimaging. The commentary notes that head-twitch behavior, a mouse proxy for human psychedelic action, depends on metabotropic glutamate 2 receptors co-expressed with 5-HT2A receptors. It also lists human neuroimaging studies of mescaline, dimethyltryptamine, and ayahuasca. The commentary raises unresolved questions about discrepancies between intravenous psilocybin studies showing decreased cerebral blood flow and oral psilocybin studies showing increased glucose metabolism.