Psychological Medicine
June 15, 2018
Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias et al.
827 citations
A single dose of ayahuasca reduced depression severity more than placebo in patients with treatment-resistant depression. Over seven days, depression scores on the Montgomery-Åsberg Depression Rating Scale were significantly lower in the ayahuasca group at days 1 and 2, and even more so at day 7. Response rates at day 7 were 64% for ayahuasca versus 27% for placebo, and remission rates showed a trend toward significance (36% vs. 7%). Effect sizes grew from day 1 to day 7, indicating sustained improvement. This is the first controlled trial to test a psychedelic substance in treatment-resistant depression, supporting ayahuasca's safety and therapeutic value when used in an appropriate setting.
PLoS ONE
February 18, 2015
Fernanda Palhano-Fontes, Kátia C. Andrade, Luís Fernando Tófoli et al.
461 citations
Ayahuasca, a psychedelic brew used traditionally by Amazonian Amerindians, significantly reduces activity in key hubs of the Default Mode Network (DMN), specifically the Posterior Cingulate Cortex (PCC)/Precuneus and medial Prefrontal Cortex (mPFC), as measured by fMRI in ten experienced subjects. Functional connectivity within the PCC/Precuneus also decreased after intake, while the orthogonality between the DMN and task-positive network showed no significant change. These findings suggest that the altered state of consciousness induced by Ayahuasca, similar to effects from psilocybin, meditation, and sleep, involves modulation of DMN activity and connectivity.
PLOS global public health
January 1, 2022
José Carlos Bouso, Óscar Andión, Jerome J Sarris et al.
115 citations
A large global survey of over 10,800 ayahuasca users from more than 50 countries found that acute physical adverse effects, primarily vomiting, occurred in 69.9% of participants, with 2.3% needing medical attention. Adverse mental health effects in the weeks or months after use were reported by 55.9% of the sample, but about 88% of those viewed these effects as part of a positive growth or integration process; around 12% sought professional support. Physical adverse effects were linked to older age at first use, having a physical health condition, higher lifetime and recent use, a prior substance use disorder diagnosis, and using ayahuasca in unsupervised settings.
Frontiers in Psychiatry
April 24, 2018
Paulo César Ribeiro Barbosa, Luís Fernando Tófoli, Michael P. Bogenschutz et al.
95 citations
Members of the Brazilian União do Vegetal (UDV) who drink ayahuasca in ceremonies show lower rates of current alcohol and tobacco use disorders compared to the general Brazilian population, even though their lifetime use of these substances is higher. Among 1,947 UDV members aged 18 and older, those who attended more ceremonies in the previous year and had longer membership reported greater reductions in alcohol and tobacco problems. The findings suggest that regular ceremonial ayahuasca use, within a religious context, is associated with reduced substance misuse, particularly for adults over 24 years old.
Frontiers in Psychiatry
June 9, 2021
Simon Ruffell, Nige Netzband, WaiFung Tsang et al.
74 citations
A naturalistic study of 63 people who participated in ayahuasca ceremonies at a retreat in the Peruvian Amazon found significant improvements in depression, anxiety, and overall psychological distress, along with increased self-compassion, immediately after the retreat and sustained at six months. Depression scores on the Beck Depression Inventory dropped from 13.9 to 6.1, anxiety scores on the State-Trait Anxiety Inventory fell from 44.4 to 34.3, and scores on the Clinical Outcomes in Routine Evaluation-Outcome Measure decreased from 37.3 to 22.3. Changes in memory valence were linked to these improvements. Epigenetic results were inconclusive but suggested further research on the SIGMAR1 gene is warranted.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
Drug and Alcohol Review
July 25, 2021
Daniel Perkins, Emérita Sátiro Opaleye, Hana Šimonová et al.
54 citations
People who consumed ayahuasca in naturalistic settings reported lower current use of alcohol and other drugs, including risky drinking, compared to those who used it less often. The more times ayahuasca was consumed, the stronger the association with never or rarely drinking alcohol and not using a range of drugs in the past month. These effects were greater for individuals with a prior substance use disorder. The strength of subjective spiritual experience, number of personal insights gained, and drinking ayahuasca with an ayahuasca church were also linked to lower substance use in some analyses. The associations remained after adjusting for religious or social group effects.
Journal of Psychoactive Drugs
September 8, 2020
Helle Kaasik, Rita C. Z. Souza, Flávia Da Silva Zandonadi et al.
54 citations
Ayahuasca brews from different traditions vary widely in their psychoactive components. Analysis of 102 samples from indigenous, religious, and neoshamanic communities showed that neoshamanic brews contain higher and more variable concentrations of DMT, likely from using larger or more variable amounts of DMT-containing plants. European samples included two instances of analog ayahuasca containing moclobemide, psilocin, DMT, and yuremamine, with very low levels of Banisteriopsis caapi alkaloids, and some used Peganum harmala and Mimosa tenuiflora. No analogs appeared in Brazilian or Santo Daime samples. The findings highlight the need for awareness and ethical self-regulation among practitioners.
Psychological medicine
March 1, 2023
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
53 citations
In a randomized, double-blind, placebo-controlled, crossover study, 24 healthy volunteers received 50 μg LSD or placebo. LSD produced psychedelic experiences, including altered consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, and increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated strongly with complex imagery, mystical experiences, and ego-dissolution. Suggestibility changes from LSD did not correlate with other effects. The results suggest the LSD state resembles psychosis and may offer a therapeutic tool, with mystical experiences linking the psychosis model and therapeutic potential. Meaning attribution appears important for the LSD psychosis model, and psychedelic-assisted therapy might benefit from suggestions that foster mystical experiences.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
January 1, 2023
Lucas Oliveira Maia, Dimitri Daldegan-Bueno, Isabel Wießner et al.
46 citations
Ayahuasca shows therapeutic potential for depression and substance use disorders, with growing preliminary evidence for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses like cancer and chronic conditions. Long-term regular use does not appear detrimental and may benefit individual and collective health. The evidence for depression and substance use disorders is most consistent, while other conditions represent promising targets requiring further rigorous investigation.
Journal of Psychopharmacology
February 1, 2022
Isabel Wießner, Marcelo Falchi-Carvalho, Lucas Oliveira Maia et al.
43 citations
A randomized, double-blind, placebo-controlled crossover study gave 24 healthy volunteers 50 micrograms of LSD or an inactive placebo and tested creativity near the drug's peak using multiple tasks. LSD changed creativity in three ways: it increased novelty, surprise, originality, and semantic distances (pattern break); decreased utility, convergent thinking, and marginally elaboration (disorganization); and increased symbolic thinking and ambiguity (meaning). The findings suggest LSD shifts cognitive resources away from normal patterns toward new ones, and that LSD-induced symbolic thinking might aid psychedelic-assisted therapy.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 1, 2022
Isabel Wießner, Rodolfo Olivieri, Marcelo Falchi et al.
42 citations
A low dose of LSD (50 μg) produces both beneficial and detrimental cognitive effects 24 hours after administration. Compared to placebo, LSD sub-acutely improved visuospatial memory and phonological verbal fluency but impaired cognitive flexibility, as measured by fewer categories achieved and more perseveration on the Wisconsin Card Sorting Test. The findings suggest that LSD-assisted therapy might be explored for conditions involving memory and language decline, such as brain injury, stroke, or dementia, while also indicating a mixed 'afterglow and hangover' profile.
Journal of Chromatography B
June 8, 2019
Rita C. Z. Souza, Flávia Da Silva Zandonadi, Donizete P. Freitas et al.
42 citations
Ayahuasca, a traditional medicine, contains active compounds like harmine and harmaline, which have garnered interest in pharmacology and drug studies. In a sample of 150 participants, 70% reported significant psychological benefits after using ayahuasca, highlighting its potential in mental health treatment. Advanced chromatography techniques revealed the unique chemical profile of ayahuasca, enhancing understanding of its effects compared to other psychedelics. This intersection of chemistry, geography, and context archaeology underscores the importance of traditional practices in modern medicine and cannabinoid research.
Journal of Psychedelic Studies
August 29, 2017
Eduardo Ekman Schenberg, Maria Angélica de Castro Comis, João Felipe Morel Alexandre et al.
39 citations
Patients with substance-related disorders who received ibogaine in a treatment program reported intense physical discomfort and a psychologically challenging experience, along with heightened memory retrieval—especially about past drug use—and vivid, dreamlike visions. The experience shared some features with other psychedelics but also differed markedly. The authors propose that ibogaine's subjective effects may function as simulations of threat and danger, drawing on an evolutionary theory of dreaming.
Journal of Psychoactive Drugs
December 7, 2020
Lucas Oliveira Maia, Dimitri Daldegan‐bueno, Luís Fernando Tófoli
33 citations
Ritual ayahuasca use during treatment for severe physical illnesses helps people accept their condition by reshaping how they understand and relate to it. Through introspection, emotional processing, recall of autobiographical memories linked to illness origin, and perspective changes, the experience facilitates illness resignification and a more balanced relationship with illness, life, and death. The findings suggest ayahuasca may promote therapeutic effects for people with physical illnesses by influencing the meanings attached to the illness.
Journal of Psychedelic Studies
April 1, 2017
Eduardo Ekman Schenberg, Maria Angélica de Castro Comis, João Felipe Morel Alexandre et al.
29 citations
A treatment combining the psychedelic alkaloid ibogaine with cognitive-behavioral therapy led to improvements in craving, personal relationships, quality of life, and self-efficacy among people with substance use disorders, including cocaine dependence. These secondary outcomes were assessed through semi-structured interviews and qualitative content analysis. The findings support the therapeutic potential of ibogaine-assisted psychotherapy for treating substance use disorders, particularly for psychostimulants like cocaine and crack cocaine, for which effective treatments are lacking.
Archives of Clinical Psychiatry (São Paulo)
January 1, 2017
Eduardo Ekman Schenberg, Luís Fernando Tófoli, Daniel Rezinovsky et al.
28 citations
A Brazilian Portuguese version of the States of Consciousness Questionnaire (SOCQ) was produced, and the 30-item Mystical Experience Questionnaire (MEQ30) was validated in a sample of 1,504 Portuguese-speaking respondents who completed an online survey. Confirmatory factor analysis supported the same four-factor structure as the original English MEQ30, with factors showing excellent to acceptable reliability: mystical (0.95), positive mood (0.71), transcendence of time/space (0.83), and ineffability (0.81). The availability of these instruments allows systematic cross-cultural research on altered states of consciousness and mystical experiences in the Brazilian Portuguese-speaking population.
Frontiers in Psychology
July 15, 2022
Alexandre Augusto de Deus Pontual, Alexandre Augusto de Deus Pontual, Luís Fernando Tófoli et al.
27 citations
Setting characteristics—social context, comfort, infrastructure, and decoration—moderate the intensity of challenging experiences during ayahuasca ceremonies, explaining 41% of the variance in challenging experience ratings across three traditions (União do Vegetal, Santo Daime, and neo-shamanic groups). Mystical experiences were less strongly associated with setting, with leadership and comfort explaining only 14% of the variance. Social context was rated highest among União do Vegetal members. In neo-shamanic groups, infrastructure, comfort, and decoration correlated more consistently with mystical experiences than in the other traditions. Maximizing setting quality reduces the likelihood of challenging experiences and modestly supports mystical experiences.
Psychopharmacology
June 1, 2022
Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes et al.
22 citations
LSD alters the stream of thought in multiple ways, increasing chaos, meaning, and abstractness at different times after ingestion. In a randomized, double-blind, placebo-controlled crossover study with 24 healthy participants, 50 μg LSD compared to placebo induced facets of mind-wandering labeled 'chaos' (discontinuity of mind, decreased sleepiness and planning), 'meaning' (deep thoughts), and 'sensation' (thoughts about odors and sounds). LSD also increased free association for abstract words, reflecting an 'abstract flow.' Chaos was strongest from 2 to 6 hours after dosing, meaning from 2 to 4 hours, sensation at 2 hours, and abstract flow at 4 hours. The findings suggest a late therapeutic window around 4 hours for psycholytic therapy.
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.
Psychoactives
June 13, 2023
Tessa Cowley‐court, Richard Chenhall, Jerome Sarris et al.
19 citations
Integrating ayahuasca experiences can be challenging and take considerable time, though working through these challenges may facilitate positive growth. A global online survey of 1630 ayahuasca drinkers (50.4% male, mean age 43) identified three main themes in integration experiences: overall appraisal (easy, challenging, or long-term/ongoing), beneficial tools (like-minded community, yoga, meditation, journaling), and challenges (feeling disconnected, returning to old life with new understandings). Findings challenge individual psychotherapy as the primary integration tool, suggesting communal and somatic elements may also be useful. An expanded definition of psychedelic integration is proposed that includes working with challenges and adjusting to life changes.
Psychoactives
October 3, 2023
Daniel Perkins, Emérita Sátiro Opaleye, José Carlos Bouso et al.
18 citations
Ayahuasca drinkers almost universally report gaining insights during their experiences, and these insights strongly predict subsequent beneficial life and lifestyle changes, including improvements in psychological wellbeing and mental health. In a large international survey of 8,907 ayahuasca drinkers, common changes attributed to ayahuasca included personal, vocational, religious or spiritual, and health-related shifts, along with healthier behaviors. Demographic factors and drinking patterns also predicted these outcomes. The findings suggest that insights and resulting life changes are central to the transformative effects of ayahuasca, occurring across diverse contexts and groups.
Frontiers in Psychology
June 23, 2021
Alexandre Augusto de Deus Pontual, Luís Fernando Tófoli, Carlos Fernando Collares et al.
14 citations
A new questionnaire, the Setting Questionnaire for the Ayahuasca Experience (SQAE), measures the physical and social context in which ayahuasca is consumed. Developed from a literature review, interviews with 19 users, and a survey of 2,994 participants, the scale's structure was tested using exploratory graph analysis and multidimensional item response theory. Six dimensions emerged—Leadership, Decoration, Infrastructure, Comfort, Instruction, and Social—though the original theoretical model fit the data better than the exploratory model. The instrument shows evidence of validity and can support future research on how setting influences the ayahuasca experience, with potential applications for studying psychedelic use more broadly.
Journal of Psychedelic Studies
February 26, 2025
Emilia Sanabria, Luís Fernando Tófoli
9 citations
Integration, the process of making sense of psychedelic experiences, is increasingly being reduced to formulaic checklists and sold as a marketable service, which risks stripping it of its potential for context-dependent personal change. This critical review traces the genealogy of integration in psychedelic medicine, contrasting contemporary Western practices with traditional Indigenous ones. The authors argue that the divergence stems from how continuous psychedelic experiences are with everyday social life and cosmology. Offering a Global South perspective, they warn against individualized, technological approaches prevalent in the US and Western Europe, and urge critical examination of assumptions behind digital psychedelia and app-based integration.
bioRxiv (Cold Spring Harbor Laboratory)
December 6, 2019
Felipe Augusto Cini da Silva, Isis M. Ornelas, Encarni Marcos et al.
9 citations
preprint
A single dose of d-LSD, a potent serotonergic agonist, increased preference for novel objects in young and adult rats several days after treatment, but did not increase preference in old animals unless followed by a 6-day exposure to enriched environment, which rescued novelty preference to young levels. Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions with alterations of long-range synapses, and that better pattern separation within enriched environment explains its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement.