Psychopharmacology
February 1, 2021
Richard J Zeifman, Nikhita Singhal, Rafael G Dos Santos et al.
79 citations
Suicidality is a major public health problem with few treatment options. In an open-label trial, 17 adults with recurrent major depressive disorder received a single dose of ayahuasca. Among the 15 who had suicidality at baseline, suicidality decreased acutely (within 40 to 180 minutes after administration) and remained lower at 1, 7, 14, and 21 days afterward. Post-acute effect sizes were large (Hedges' g = 1.31–1.75), with the largest effect at 21 days (g = 1.75). When administered in an appropriate context, ayahuasca may produce rapid and sustained reductions in suicidality. The authors call for randomized, double-blind studies with larger samples to confirm these early findings.
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.
Journal of clinical psychopharmacology
María Gómez-sousa, Daniel F Jiménez-garrido, Genís Ona et al.
24 citations
Among 40 first-time ayahuasca ceremony participants, 7 reported intense challenging psychological effects. Four of those 7 had a pre-existing psychiatric diagnosis; one month after the ceremony, two no longer met diagnostic criteria and the other two showed considerably reduced symptoms, with effects persisting at six months. Poor setting and guidance contributed to some reactions. Six of the seven did not use ayahuasca again during the study. The findings suggest that acute negative psychological reactions during ayahuasca ceremonies can sometimes be followed by positive long-term effects, highlighting the need for prospective research on safety and contextual factors.
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.
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.
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.
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.
Advances in experimental medicine and biology
January 1, 2021
Jose Carlos Bouso, Genís Ona, Rafael G Dos Santos et al.
6 citations
Research on psychedelic drugs for therapeutic use has grown, driven by the need for innovative psychiatric treatments. Clinical trials have assessed psilocybin and ayahuasca for mental disorders including major depression. This chapter reviews the history and terminology of psychedelic research, analyzes recent clinical trials administering these drugs to patients, describes neurobiological mechanisms that may underlie therapeutic effects, and notes that psychedelics are commonly used as adjuncts to psychotherapy. The chapter concludes by suggesting future challenges for this field.
European archives of psychiatry and clinical neuroscience
October 28, 2024
Kaike Thiê da Costa Gonçalves, Vagner Deuel O de Tavares, Maria Luiza de Morais Barros et al.
5 citations
A systematic review of 29 studies examined whether the psychoactive effects of ketamine are linked to its therapeutic benefits for psychiatric disorders. About half of the studies (51.72%) found a positive relationship between ketamine-induced altered states of consciousness and clinical outcomes, while 44.83% found no link, and one study found a negative association. For mood disorders like major depressive disorder and bipolar disorder, 48% of studies showed a positive relationship and 48% showed none. All three studies on substance use disorder reported a positive correlation. The authors conclude the relationship remains uncertain due to high variability across studies.
Journal of psychopharmacology (Oxford, England)
May 31, 2026
Anna Beatriz Vicentini, Caio César De Paula, José Augusto Silva Reis et al.
A systematic review of 48 studies (14 experimental, 34 observational) covering 2016–2024 found that classic psychedelics—such as psilocybin and ayahuasca—most consistently increase the personality trait Openness and reduce Neuroticism. Changes in Extraversion, Agreeableness, and Conscientiousness were more variable. Microdosing was linked to modest reductions in Neuroticism and higher Absorption. Most studies used the Five-Factor Model. The findings suggest psychedelics can promote lasting personality changes, but contradictory results remain, and future research should combine experimental and naturalistic designs with longer follow-ups.
Journal of psychopharmacology (Oxford, England)
March 9, 2026
Caio César De Paula, Anna Beatriz Vicentini, Lorena Terene Lopes Guerra et al.
A systematic review of 16 studies found that ayahuasca has distinct short- and long-term cognitive effects. In the short term, improvements in working memory and cognitive flexibility were observed, linked to neurochemical modulation of cortical networks. Observational studies reported increased empathy and emotion recognition, while experimental studies only found reduced reaction times in social cognition tasks. Long-term studies generally found no neuropsychological deficits, with some reporting improved memory and executive function. The review notes methodological limitations including small sample sizes, varied protocols, and potential learning effects, calling for more controlled, randomized studies.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2026
Isabel Werle, Francisco S Guimarães, Rafael G Dos Santos et al.
Ayahuasca, a brew containing the psychedelic DMT, helps rodents overcome persistent and generalized fear memories by boosting brain-derived neurotrophic factor (BDNF) signaling in the infralimbic (IL) region of the medial prefrontal cortex. In rats exposed to stress or high-intensity fear conditioning, repeated ayahuasca (0.3 mg/kg DMT) enhanced extinction learning and its retention, and reduced fear generalization. These effects were blocked by infusing an anti-BDNF antibody or a TrkB receptor antagonist into the IL cortex. The reduction in fear generalization depended on BDNF in females but not males. The findings suggest psychedelics may aid in treating difficult-to-extinguish trauma memories, such as those in PTSD.
IBRO neuroscience reports
December 1, 2024
Gabriela N Vaz, Flávia C Turcato, Isabel A V Lima et al.
Mice lacking the PI3Kγ gene did not respond to standard doses of ketamine or to classic antidepressants such as imipramine and fluoxetine, as measured by the forced swimming test. This unresponsiveness required a chronic deficiency of the PI3Kγ-mediated pathway, not just acute inhibition. The findings suggest PI3Kγ plays a role in antidepressant activity and may be involved in treatment resistance observed in some patients with major depressive disorder.