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.
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.
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.
Therapeutic Advances in Psychopharmacology
January 1, 2019
Juliana Mendes Rocha, Flávia de Lima Osório, José Alexandre S. Crippa et al.
44 citations
A systematic review of 8 studies found that serotonergic hallucinogens such as LSD and psilocybin reduce the recognition of negative emotions in facial expressions and modulate amygdala activity in response to these stimuli. These effects correlated with antidepressive benefits in patients. The drugs were well tolerated. Although sample sizes were small, the results suggest that serotonergic hallucinogens may reverse deficits in emotion recognition associated with anxiety and mood disorders.
Frontiers in Psychiatry
June 16, 2021
Dóra Révész, Genís Oña, Giordano Novak Rossi et al.
42 citations
During the first strict COVID-19 lockdown (April–July 2020), people who had used psychedelic drugs regularly (more than once per six months) reported less psychological distress, less peritraumatic stress, and more social support than occasional or non-users. Regular users also scored higher on novelty-seeking and self-transcendence and lower on cooperativeness. The findings suggest that lifetime psychedelic use may be a protective factor for mental health under stressful confinement, or that pre-existing personality traits make some individuals more likely to use psychedelics. The study surveyed 2,974 English, Portuguese, and Spanish speakers online.
Frontiers in Psychiatry
August 6, 2021
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia de Lima Osório et al.
37 citations
In two small randomized placebo-controlled trials, ayahuasca did not consistently change personality traits. One trial found a significant increase in Openness to experience 21 days after ayahuasca, but the other trial showed no such effect. Baseline differences in Openness between groups and small sample sizes may explain the inconsistent results. The findings suggest that ayahuasca's influence on personality is not robust across studies, and further research in clinical populations is needed.
Molecules
April 29, 2020
Gabriela de Oliveira Silveira, Rafael G. Dos Santos, Felipe Rebello Lourenço et al.
36 citations
Ayahuasca tea, a hallucinogenic beverage used in religious and therapeutic contexts, was tested for the stability of its main alkaloids—DMT, harmine, tetrahydroharmine, and harmaline—under three storage conditions: one year in a refrigerator (plastic or glass containers), seven days at 37°C (simulating mail transport), and three freeze-thaw cycles. DMT showed no significant degradation in any condition. However, harmala alkaloids exhibited substantial variation, including degradation and concentration increases, likely due to inter-conversion and leaching from tea precipitate. Thus, quantifying alkaloids before administration in controlled studies is essential.
Biomolecules
November 2, 2022
Giordano Novak Rossi, Lorena T. L. Guerra, Glen B. Baker et al.
29 citations
Ayahuasca, a psychoactive brew used in South American rituals, contains DMT from Psychotria viridis and MAO-inhibiting β-carbolines from Banisteriopsis caapi. Preclinical and clinical evidence suggests its antidepressant effects involve complex modulation of serotoninergic, glutamatergic, dopaminergic, and endocannabinoid systems, along with interactions with VMAT, TAAR1, and sigma-1 receptors. The brew also appears to beneficially modulate inflammatory and neurotrophic factors, leading to neuroprotective and neuroplastic effects. This review summarizes current knowledge of these molecular interactions and their relation to ayahuasca's potential antidepressant properties.
Expert Opinion on Drug Safety
April 15, 2022
Giordano Novak Rossi, Jaime E. C. Hallak, José Carlos Bouso Saiz et al.
24 citations
In the reviewed studies, no serious adverse events were linked to psilocybin or LSD administration. Most side effects were anticipated, manageable, and temporary. However, concerns persist about certain effects like dissociation, paranoia, and confusion. The authors conclude that larger randomized controlled trials are needed to confirm therapeutic benefits and further assess safety and tolerability.
Human Psychopharmacology Clinical and Experimental
February 2, 2022
Rafael G. Dos Santos, Juliana Mendes Rocha, Giordano Novak Rossi et al.
20 citations
A post-hoc analysis of two small randomized placebo-controlled trials measured endocannabinoid (anandamide, AEA; 2-arachidonoylglycerol, 2-AG) plasma levels in healthy volunteers and in volunteers with social anxiety disorder (SAD) after a single oral dose of ayahuasca or placebo. In the SAD group, ayahuasca intake was associated with a significant difference in AEA concentrations over time, and near-significant increases in AEA were observed at 90 and 240 minutes after intake. No definitive conclusions could be drawn due to high interindividual variability and small sample sizes. Larger studies are needed to clarify ayahuasca's effects on the endocannabinoid system.
Expert Opinion on Drug Safety
March 18, 2022
Giordano Novak Rossi, Isabella Caroline Da Silva Dias, Glen B. Baker et al.
17 citations
In controlled settings, ayahuasca administration appears relatively safe, with no serious adverse events reported. Common side effects include nausea, vomiting, headaches, and temporary increases in heart rate and blood pressure. Research on ayahuasca's antidepressant effects is still early, lacking large, robust clinical trials. Major obstacles to its therapeutic use include dose standardization, legal prohibition of its alkaloids, and questions about compensating traditional communities if ayahuasca becomes an approved medicine.
Talanta
December 9, 2020
Gabriela de Oliveira Silveira, Felipe Rebello Lourenço, Ana Miguel Fonseca Pego et al.
15 citations
A new sample-preparation method uses eucalyptus essential oil, instead of conventional organic solvents, to extract four ayahuasca-related compounds (DMT, harmine, harmaline, and tetrahydroharmine) from human plasma. After optimizing the procedure with factorial experiments, the method was validated and applied to 13 real plasma samples. Detection limits were ≤1.0 ng/mL, and the method was linear up to 150 ng/mL. Recovery averaged 50%, and matrix effects showed ion suppression of 56–83%. The approach is simple, fast, and environmentally friendly, offering a green alternative for forensic and clinical drug analysis.
European archives of psychiatry and clinical neuroscience
February 1, 2023
Giordano Novak Rossi, Jaime E C Hallak, Glen 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.
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.
Journal of Clinical Psychopharmacology
March 14, 2022
Juliana Mendes Rocha, Giordano Novak Rossi, Flávia L. Osório et al.
11 citations
Psychedelics show promise in treating brain disorders, with a study involving 200 participants revealing a 60% reduction in symptoms of depression and anxiety after a single dose. Tryptophan, a key amino acid, plays a crucial role in serotonin production, which is vital for mood regulation. Biochemical analysis and advanced sensing techniques have enhanced understanding of these substances' effects on the brain, highlighting their potential as innovative therapies for mental health challenges. This groundbreaking approach could reshape treatment paradigms for various conditions.
European archives of psychiatry and clinical neuroscience
March 1, 2025
Arilton Martins Fonseca, Rafael Guimarães Dos Santos, Lívia Soman de Medeiros et al.
10 citations
Long-term ritualistic ayahuasca use, spanning over 20 years, does not impair cognition and may be linked to better working memory compared to short-term use. In a study of 48 participants from a Santo Daime church in Brazil, experienced users (over 20 years) scored higher on tests of verbal and visuospatial working memory than beginners (under 3 years). No evidence of cognitive decline was found among ayahuasca users. The control group, matched by sex, age, and education, showed similar cognitive performance. The brew's botanical identities and alkaloid content were confirmed.
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.
Analytica chimica acta
May 1, 2024
André Luis Fabris, Stig Pedersen-Bjergaard, Elisabeth Leere Øiestad et al.
9 citations
A 96-well plate extraction method called parallel artificial liquid membrane extraction (PALME) can be made greener by replacing organic solvents with an essential oil. Fourteen essential oils were tested; the blend smart & sassy gave the best recovery for multiple drugs of abuse in plasma, including amphetamines, synthetic cathinones, and designer benzodiazepines. After optimization, the method achieved a linear range of 1-100 ng/mL, accuracy within ±16.4%, and limits of detection between 0.1 and 0.75 ng/mL. The technique eliminated hazardous organic solvents, provided effective sample clean-up, and met international validation guidelines, offering a sustainable tool for toxicological analysis.
Scientific Reports
September 11, 2023
José Carlos Bouso, Dóra Révész, Genís Oña 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 Oña, 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
Lucas Silva Rodrigues, José Augusto Silva Reis, Giordano Novak Rossi et al.
8 citations
A single dose of ayahuasca, a plant hallucinogen containing N,N-dimethyltryptamine and harmine, was given with psychological support to 11 college students who drank alcohol harmfully. The treatment was well tolerated and produced strong psychoactive effects. Days of alcohol consumption per week dropped from about 2.9 to 2.1 between weeks 2 and 3, but this reduction was not statistically significant after correcting for multiple comparisons. No other measures—craving, anxiety, impulsivity, self-esteem, or social cognition—showed significant changes, except faster reaction time on an empathy task. The small sample and mild baseline drinking likely limited the findings. The study demonstrates the protocol is feasible for future larger trials.
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.
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.
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.