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.
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.
Front Psychiatry
November 6, 2024
Cristiano Chaves, Rafael G. Dos Santos, Serdar M. 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.
European Neuropsychopharmacology
September 1, 2009
D. Almeida Prado, Joel Porfírio Pinto, José Alexandre S. Crippa et al.
9 citations
Ayahuasca, a traditional Amazonian brew, shows promise in psychiatry, with 66% of participants reporting significant improvement in depressive symptoms after treatment. This study involved 100 individuals seeking relief from mental health issues. Participants experienced enhanced emotional well-being and altered perspectives on life, suggesting a blend of psychological and philosophical enlightenment. The findings highlight ayahuasca's potential as a medicinal tool within the broader context of psychedelics and drug studies, offering new insights into the intersection of psychology, art, and anthropology in understanding human experience.
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.
Experimental and Clinical Psychopharmacology
November 4, 2021
Tânia Cristina Libânio, R. Eufrásio, Suzy S Niigaki et al.
6 citations
Harmine, a component of the psychedelic brew ayahuasca, impairs memory in emotional contexts in rats, and even untreated rats housed with harmine-treated rats show memory deficits. In experiments using contextual and tone fear conditioning and a plus-maze discriminative avoidance task, harmine at 10 mg/kg impaired contextual fear conditioning, and all doses (5, 10, or 15 mg/kg) impaired discriminative avoidance. Untreated rats housed in cages with harmine-treated rats also showed memory deficits across all tasks, suggesting that social context and cohabitation can influence the drug's behavioral effects.
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
PLoS ONE
October 13, 2025
Francisco González-espejito, Laura Esteban Rodríguez, Eduardo J. Pedrero Pérez et al.
Ibogaine, a compound from the iboga plant used in traditional Bwiti rituals, shows promise for treating opioid dependence and neurological conditions, but existing tools fail to capture its dream-like subjective effects. A new 70-item Ibogaine Experience Scale (IES) was developed from a prior qualitative study and tested with 499 participants in neuropsychiatric and substance use treatment settings. The final scale has seven factors—including narrative visions, visual changes, discomfort, cosmic visions, introspection, somatosensory sensitivity, and dissociation—explaining 53.9% of variance, with excellent statistical fit and high internal consistency. The IES offers a reliable way to measure ibogaine's multidimensional effects for research and clinical use.
Braz J Psychiatry
September 29, 2025
José Augusto S. Reis, Giordano N. Rossi, Anna Beatriz V. Zacharias et al.
A case report describes an instance of acute suicidal behavior that occurred after a participant ingested ayahuasca in a clinical trial setting. The report details the circumstances and clinical presentation of this adverse event, highlighting a potential risk associated with ayahuasca use even within a controlled research environment. The authors suggest that such reactions, though rare, warrant careful screening and monitoring of participants in psychedelic research.
Journal of Psychedelic Studies
September 4, 2025
Giordano Novak Rossi, Rishma S. I. Khubsing, Eline Haijen et al.
Both a single ayahuasca ceremony and a single breathwork session led to lasting improvements in cognitive flexibility, emotion regulation, positive affect, and sleep quality over three months. Improvements in cognitive flexibility appeared before changes in emotion regulation, partially supporting the idea that cognitive shifts may drive later emotional gains. The two treatments did not differ in their overall benefits, and the role of participants' experience and motivation remains unclear. The findings suggest that both practices can promote psychological well-being, but further research is needed to clarify the mechanisms and temporal order of these effects.
Psychoactives
July 15, 2025
Bianca Villanova, Giordano Novak Rossi, Lorena Terene Lopes Guerra et al.
Ayahuasca, a psychoactive brew containing DMT and harmine, may reduce pain and inflammation. A systematic review of 29 preclinical studies found that ayahuasca and its alkaloids, especially harmine, produce antinociceptive effects and shift cytokine balance toward anti-inflammatory. More research is needed.
Psychoactives
November 21, 2022
Rafael G. Dos Santos, Jaime E. C. Hallak
Ayahuasca, a traditional Amazonian brew containing the hallucinogen DMT, shows promise for treating mental health disorders. Over the past twenty years, research has increasingly explored its therapeutic potential, particularly for depression, anxiety, and addiction. The brew's active compounds interact with serotonin receptors in the brain, potentially promoting neuroplasticity and emotional processing. Clinical studies suggest that ayahuasca can produce rapid and sustained reductions in depressive symptoms, often after a single dose. However, the authors note that more rigorous randomized controlled trials are needed to confirm these effects and understand the underlying mechanisms. The cultural and spiritual context of ayahuasca use also plays a role in its therapeutic outcomes.