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.
Archives of Clinical Psychiatry (São Paulo)
February 1, 2018
Rafael G. Dos Santos, Rafael Faria Sanches, Flávia de Lima Osório et al.
37 citations
Ayahuasca, a botanical hallucinogenic preparation containing β-carboline alkaloids and DMT, was well tolerated by patients with treatment-resistant major depressive disorder in an open-label trial. Symptom reductions lasted only a few weeks, but most patients considered the experience among the most important of their lives, even 4 to 7 years later. This is the first long-term follow-up of a clinical sample from an ayahuasca trial, suggesting that while acute antidepressant effects are short-lived, the subjective significance endures.
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.
Journal of Psychedelic Studies
April 1, 2017
Rafael G. Dos Santos, José Carlos Bouso, Jaime E. C. Hallak
36 citations
Ibogaine, a naturally occurring hallucinogenic alkaloid, may reduce drug craving and withdrawal. A systematic review of human studies identified eight relevant papers: seven open-label case series and one randomized, placebo-controlled trial. The case series suggest that one or a few ibogaine treatments can significantly reduce withdrawal, craving, and drug self-administration in dependent individuals, with effects lasting from 24 hours to weeks or months. However, the clinical trial found no significant effects of noribogaine on opiate or opioid withdrawal. Given the need for fast-acting, sustained treatments for opiate and cocaine dependence, further controlled trials of ibogaine and noribogaine are warranted.
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.
Journal of Psychoactive Drugs
May 28, 2022
Maja Kohek, Genís Oña, Michiel van Elk et al.
25 citations
Regular participation in ayahuasca ceremonies is not linked to relevant health harms. Compared to normative Dutch data, 377 participants (50.1% women, mean age 48.8 years) showed better general well-being, fewer chronic or lifestyle-related diseases, more physical activity, and a more balanced diet. During the COVID-19 pandemic, they used less alcohol. Although they used more illegal drugs than the general population, they did not report associated harms. This evidence could inform drug policymakers in developing evidence-based public policies.
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.
bioRxiv (Cold Spring Harbor Laboratory)
January 27, 2017
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
22 citations
preprint
A single dose of ayahuasca produced significant antidepressant effects in patients with treatment-resistant depression compared to placebo. Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), was significantly lower in the ayahuasca group at one, two, and seven days after dosing. Effect sizes increased over time, reaching a Cohen's d of 1.49 at day seven. Response rates were significantly higher in the ayahuasca group at day seven (64% vs. 27%), and remission rates were marginally significant (36% vs. 7%). This controlled trial supports the safety and therapeutic value of ayahuasca in treating depression.
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.
Journal of Psychedelic Studies
July 25, 2018
Rafael G. Dos Santos, Scotty Enyart, José Carlos Bouso et al.
18 citations
A man who had long experienced aphantasia (the inability to form voluntary mental images) reported modest but sustained improvements in his visual imagery after a single dose of ayahuasca, a botanical hallucinogen rich in DMT. The improvements were attributed to possible biological and psychological processes, including stimulation of cortical 5-HT2A receptors, increased activity in the visual cortex, and resolution of psychological trauma from a difficult relationship with his father. The case suggests that 5-HT2A agonists like ayahuasca may offer a path to explore treatments for aphantasia, though further trials are needed.
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.
Talanta
December 9, 2020
Gabriela de Oliveira Silveira, Felipe Rebello Lourenço, Ana Miguel Fonseca Pego et al.
15 citations
A novel approach using chromatography achieved a 95% accuracy rate in analyzing human plasma for psychedelics. In a factorial experiment with 150 samples, the box–Behnken design optimized solvent use, enhancing detection capabilities in forensic toxicology and drug analysis. This innovative method significantly improves analytical chemistry practices, ensuring reliable results in drug studies. The findings underscore the potential of advanced chromatographic techniques to refine how substances are identified and quantified, paving the way for more effective applications in both clinical and legal contexts.
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.
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.
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 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 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 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.
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.