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Rafael G. Dos Santos

Clinics Hospital of Ribeirão Preto

64 papers in the library · 4,761 citations · publishing 2006-2026

Papers

Anxiety, panic, and hopelessness during and after ritual ayahuasca intake in a woman with generalized anxiety disorder: A case report

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.

Neural Network Modulation of Ayahuasca: A Systematic Review of Human Studies

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.

Subjective Effects of a Single Dose of Ayahuasca among College Students with Harmful Alcohol Use: Qualitative Analysis of Participant Accounts

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.

Effects of ayahuasca on fear and anxiety: cross-talk between 5HT1A and 5HT2A receptors

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.

Guidelines for Establishing Safety in Ayahuasca and Ibogaine Administration in Clinical Settings

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.

Clinical pharmacology of ayahuasca: potential applications and future considerations

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.

Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling

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.

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments

Brazilian Journal of Psychiatry June 16, 2026 Daniel B.a. Prado, Matheus T. Rossignoli, Rafael N. Ruggiero et al.

In a rat model of schizophrenia-like symptoms induced by ketamine, the combination of cannabidiol and sodium nitroprusside given during brain development prevented hyperactivity and memory problems in both sexes, while each drug alone had limited effects. The model produced different symptoms in males and females: females showed greater hyperactivity and long-term memory deficits, whereas males showed reduced pleasure-seeking and short-term memory impairments. The combined treatment was more effective in females, and distinct behavioral patterns were seen between sexes. This suggests that a combination of these two compounds may offer a sex-specific preventive strategy for schizophrenia symptoms.

Personality, not cognition, distinguishes chronic ayahuasca and cannabis users from non-users

European Neuropsychopharmacology February 12, 2026 José Carlos Bouso, Óscar Andión, Sabela Fondevila Estévez et al.

Regular users of ayahuasca or cannabis show no detectable lasting impairments in executive function or working memory compared to non-users, after abstaining for 10-30 days. Personality traits, not cognition or psychopathology, best distinguish the groups: ayahuasca users score higher on self-transcendence and lower on harm avoidance and persistence, while cannabis users score higher on novelty seeking and impulsive nonconformity and lower on introvertive anhedonia. Although ayahuasca users had a higher lifetime prevalence of mood and anxiety disorders, they showed no current psychopathological symptoms. The study's cross-sectional, self-selected, non-treatment-seeking sample may limit generalizability.

The Ibogaine Experience Scale (IES): Development and psychometric properties of a multidimensional measure of ibogaine’s subjective effects

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.

Comparative effects of ayahuasca and breathwork on self-reported cognitive flexibility, emotion regulation, positive affect, and sleep quality

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.

Ayahuasca, Pain, and Inflammation: A Systematic Review of Preclinical Studies

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.

Natural Hallucinogens in Mental Health

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.