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 Ona, 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.
Psychopharmacology
June 1, 2022
Genís Ona, Juliana Mendes Rocha, José Carlos Bouso et al.
41 citations
Ibogaine, a hallucinogenic and psychostimulant alkaloid from the African shrub Tabernanthe iboga, is known for its anti-addictive properties, but its use is associated with serious adverse events and fatalities. A systematic review of 18 studies from 2015 to 2020 found highly heterogeneous results regarding the product used and dosages. Adverse events were classified as acute effects (within 24 hours) and persistent cardiac, psychiatric, and neurological alterations. The review highlights the need for phase I clinical trials to establish safety for standardized ibogaine products, and for research to identify vulnerable populations and develop effective screening and clinical procedures.
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.
November 22, 2013
Xavier Fernández, Rafael G. Dos Santos, Marta Cutchet et al.
37 citations
Ayahuasca shows promise in reducing anxiety and altering personality traits, with a study involving 80 participants revealing a significant decrease in anxiety levels for 70% of users. Participants reported enhanced emotional resilience and lower worry, suggesting ayahuasca's potential role in clinical psychology and psychiatry. The effects may stem from its influence on neurotransmitter receptors, paralleling findings in cannabis research. The temperament and character inventory indicated shifts towards more adaptive personality profiles, highlighting the therapeutic potential of psychedelics in addressing psychopathology.
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 Ona, 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.
British Journal of Pharmacology
June 1, 2024
Isabel Werle, Laura M M Nascimento, Aymee L A Dos Santos et al.
21 citations
A single oral dose of ayahuasca containing 0.3 mg/kg of DMT increased within-session extinction of contextual freezing behavior in rats without affecting recall; two consecutive daily doses enhanced extinction recall. These effects occurred for both 1- and 21-day-old memories in males and females, independent of changes in anxiety or general exploratory activity. Blocking 5-HT2A receptors in the infralimbic cortex prevented within-session extinction, while blocking 5-HT1A receptors prevented between-session extinction. The findings highlight complementary mechanisms by which ayahuasca facilitates behavioral suppression of aversive memories, suggesting potential benefits for stress-related disorders.
European Archives of Psychiatry and Clinical Neuroscience
October 1, 2023
Juliana Mendes Rocha, José A S Reis, José Carlos Bouso et al.
21 citations
Ibogaine, a psychoactive alkaloid from the west-African shrub Tabernanthe iboga, is increasingly sought in Western cultures for its claimed anti-addictive properties, though evidence remains preliminary. Its use often occurs without medical supervision in uncontrolled settings and has been linked to severe adverse events. This systematic review evaluated clinical studies of ibogaine, focusing on administration settings to identify criteria promoting safer use. Following PRISMA guidelines, searches in PubMed, Scielo, ClinicalTrials.gov, and Core.ac.uk retrieved clinical studies published through November 17, 2022; 12 sources were synthesized. The review concludes that controlled settings with trained professionals and equipment for rigorous medical, psychiatric, and cardiac monitoring are essential for patient safety.
Journal of psychopharmacology (Oxford, England)
December 1, 2023
Genís Ona, Ingrid Reverte, Giordano N. Rossi et al.
20 citations
Ibogaine and its main metabolite, noribogaine, modulate several brain targets associated with substance use disorders. Rather than having a single key mechanism, their anti-addictive action appears to arise from a complex modulation of multiple receptor systems, creating potential beneficial synergies. This understanding comes from a review of theoretical and experimental studies published up to July 2022. The authors suggest that future research should apply polypharmacology approaches to better describe the multifaceted patterns of this multi-target drug, which could guide both mechanistic and therapeutic studies.
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.
Drug and Alcohol Review
February 1, 2023
Borja J Rodríguez-cano, Maja Kohek, Genís Ona et al.
17 citations
Ibogaine, a psychoactive alkaloid from the Tabernanthe iboga plant traditionally used in Bwiti culture, has been used experimentally to treat substance use disorders (SUD) since 1962. Interviews with 13 people who self-treated their SUD with ibogaine revealed that the drug's therapeutic benefits arise not only from its pharmacology but also from the subjective experience it induces. Participants reported that ibogaine evoked interpersonal and transpersonal experiences, autobiographical memories, and personal insights. These effects, along with preparation, integration, and motivation for lifestyle change, appear to help individuals cope with their SUD, particularly given limited alternative treatment options.
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 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.
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.
Psicologia Teoria e Pesquisa
December 1, 2006
Rafael G. Dos Santos, Célia Carvalho de Moraes, Adriano Furtado Holanda
15 citations
A case study evaluates the possible role of ayahuasca use in a religious context as an aid in reducing the abuse of psychoactive substances. An open interview was conducted with a regular user of cocaine, nicotine, and alcohol who stopped this behavior after coming into contact with ayahuasca in a ritualized setting. The case was analyzed by comparing it with existing literature. A relationship was traced between the start of ayahuasca use and the interviewee's abandonment of cocaine, nicotine, and alcohol, based on the evaluation of symbolic representations and descriptions of her first experiences with the beverage.