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.
BMC Psychiatry
October 28, 2019
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
17 citations
A commentary expands on a prior review of treatments for psychiatric conditions in end-stage cancer patients, noting that evidence for classic hallucinogens like psilocybin and LSD was omitted. It briefly reviews recent placebo-controlled, double-blind, cross-over clinical trials showing that single or few doses of LSD and psilocybin were associated with rapid and sustained reductions in depressive and anxiety symptoms in patients with end-stage cancer and other life-threatening diseases, such as Bechterew's, Parkinson's, and Celiac disease. The authors suggest these substances appear well tolerated and produce rapid therapeutic effects with few doses, and call for large-scale, prospective, multi-site studies to better understand their therapeutic potential.
Drugs Education Prevention and Policy
May 7, 2019
Marc Aixalà, Genís Oña, Òscar Parés et al.
16 citations
A survey of 564 natural psychoactive drug (NPD) users from 52 countries found that the typical user is a well-educated adult who uses these substances sporadically. Psilocybe mushrooms (88.5%) and ayahuasca (51%) were the most used. Users reported positive life influences and good mental health. The authors argue that NPDs differ from synthetic new psychoactive substances (NPSs) in safety and use patterns, and should not be legally classified together with NPSs.
Archives of Clinical Psychiatry (São Paulo)
April 1, 2020
José Carlos Bouso, I. Fornís, Mireia Ventura et al.
15 citations
The purity of iboga products sold online and by treatment providers is highly variable. Analysis of 16 samples—including root bark, total alkaloids, purified total alkaloids, and ibogaine hydrochloride—found ibogaine content ranging from 0.6% to 11.2% in root bark, 8.2% to 32.9% in total alkaloid products, 73.7% in one purified sample, and 61.5% to 73.4% in ibogaine hydrochloride samples. One sample contained no iboga alkaloids. Almost all samples also contained other alkaloids and unknown substances. The variability poses risks for correct dosing and potential adverse reactions or interactions.
Current Medicinal Chemistry
December 13, 2019
Genís Oña, José Carlos Bouso
15 citations
Developing highly selective drugs for central nervous system disorders has proven unsuccessful. Multi-target ligands, which act on multiple biological pathways, are now proposed as treatments offering better efficacy and safety. Natural products, including psychoactive drugs like ayahuasca and cannabis, exemplify this multi-target approach and show therapeutic promise for psychiatric and neurological conditions. This text describes how research on psychoactive drugs can be combined with polypharmacology, using ayahuasca and cannabis as examples, and discusses the advantages and disadvantages of this strategy.
Archives of Clinical Psychiatry (São Paulo)
August 1, 2017
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
15 citations
Ayahuasca, a psychoactive plant-based concoction traditionally used by indigenous groups in the Amazon, is increasingly used worldwide. In controlled settings, its administration appears safe, with few adverse reactions; more frequent adverse events occur in uncontrolled environments. Prolonged psychotic reactions are rare and mainly affect susceptible individuals. Studies in animals and humans suggest antidepressive, anxiolytic, and antiaddictive effects, but controlled clinical trials are lacking. People with a personal or family history of psychotic disorders should avoid ayahuasca.
Journal of Psychedelic Studies
April 1, 2017
Clare Wilkins, Rafael G. Dos Santos, Jordi Solà et al.
15 citations
A woman on methadone maintenance treatment for 17 years self-treated with several low and cumulative doses of ibogaine over 6 weeks. Each dose attenuated withdrawal symptoms for hours and reduced tolerance to methadone until all withdrawal signs disappeared. No serious adverse effects occurred, and QTc measures never reached clinically significant scores. Twelve months after treatment, she was no longer on methadone maintenance. This first case report suggests that low and cumulative ibogaine doses may reduce withdrawal symptoms in patients on methadone maintenance treatment, though clinical trials are lacking.
Frontiers in Psychiatry
December 19, 2023
Jonathan David, José Carlos Bouso, Maja Kohek et al.
14 citations
More than half of people who participate in ayahuasca ceremonies report having a subjective sense of death during the experience, termed Ayahuasca-induced Personal Death (APD). These experiences are typically strong and transformative, associated with an increased sense of transcending death and greater certainty that consciousness continues after death. APDs are not linked to demographics, personality, or psychopathology, but are associated with greater environmental concern, improved ability to cope with life problems, and a heightened sense of life fulfillment. The findings suggest these death experiences may be a mechanism for psychedelics' long-term positive effects.
The International journal on drug policy
December 1, 2021
Maja Kohek, Constanza Sánchez Avilés, Oriol Romaní et al.
14 citations
Cannabis has a long history of medical, recreational, industrial, and spiritual uses. This paper reports on ethnographic fieldwork in rural Catalonia, where a phenomenological community regularly uses ancient psychoactive plants, including cannabis and ayahuasca, in ritual contexts. The rituals serve as effective harm reduction techniques, strengthening community bonds and generating beneficial effects for individuals and communities. Participants view these practices as spiritual or religious, and as forms of self-care and community-care, rather than involving dependence or addiction. The authors argue that international drug policies, which claim to be evidence-based, overlook the benefits of non-problematic drug use and could be improved by incorporating ethnographic findings on the spiritual and community dimensions of drug use.
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.
ACS Chemical Neuroscience
October 6, 2020
Genís Oña, 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.
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.
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.
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.
Preprints.org
January 24, 2019
Genís Ona, José Carlos Bouso
8 citations
preprint
The current crisis in psychopharmacology has deep historical roots and requires innovative approaches. The therapeutic use of psychedelic drugs offers a promising and integrative treatment with enduring effects for mental health problems.
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.
Qeios
April 27, 2020
Genis Oña, José Carlos Bouso
7 citations
Psychiatry faces major challenges, as many mental disorders still lack effective treatments despite recent innovations. The therapeutic use of psychedelic drugs within psychotherapeutic settings offers a promising, integrative treatment that produces enduring effects for patients. Psychedelic psychotherapy combines complex pharmacological action with enhanced psychotherapeutic interventions, representing an important innovation in the field.
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.
Frontiers in psychiatry
January 1, 2022
Otto Simonsson, José Carlos Bouso, Florian Kurth et al.
6 citations
The corpus callosum, a brain structure connecting the two hemispheres, was thicker in the isthmus region among 22 ayahuasca users compared to 22 matched controls. A positive correlation was observed between callosal thickness in the rostral body and the number of past ayahuasca sessions, though neither finding survived correction for multiple comparisons. No brain region was thicker in controls than in ayahuasca users, and no region was negatively linked to ayahuasca use. This provides preliminary evidence of an association between ayahuasca use and callosal structure, but replication with larger samples and longitudinal designs 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.
Revista de Antropología Social
November 20, 2023
Maja Kohek, José Carlos Bouso, Genís Oña
3 citations
A woman who migrated from the Brazilian rainforest to Barcelona seventeen years ago became a healer working with ayahuasca, kambó (frog venom), and sananga (herbal eye drops). The case study examines authenticity, communitas, and self-care. Shamanism, religion, and health are fluid and dynamic processes that interact with and absorb influences from their surroundings. Exploring compatibilities between beliefs and practices from different traditions mixed with biomedical approaches broadens understanding of relationships among religion or spirituality, health, and well-being. The article concludes by proposing a contribution from medical anthropology to challenges posed by the globalization of ayahuasca practices.