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.
Journal of psychoactive drugs
January 10, 2025
Ana Cláudia Mesquita Garcia, Lucas Oliveira Maia, Everson Meireles et al.
8 citations
A survey of 517 Brazilian adults found that people who never or almost never used psychedelics reported higher death anxiety than those who had used them. The study also validated the Death Anxiety Scale in Brazil. Death transcendence—especially creative and religious forms—consistently explained variations in death anxiety across all models. A negative relationship emerged between death anxiety and mystical and religious factors of death transcendence. The authors interpret that psychedelics themselves do not directly reduce death anxiety; rather, they may facilitate experiences of transcending death—the sense of continuity beyond physical death, whether spiritual or symbolic—which in turn helps lower death anxiety.
Biological Trace Element Research
June 5, 2020
Ivanilce Cristina Guimarães, Luís Fernando Tófoli, Alessandra Sussulini
7 citations
Ayahuasca, a brew made from two Amazonian plants, is consumed worldwide, raising safety concerns about its oral use. This study analyzed the elemental composition of ready-to-consume ayahuasca samples from Brazilian religious groups. Concentrations of macroelements (Ca, Mg, K, P) and microelements (Li, Al, Mn, Fe, Co, Cu, Zn, As, Cd, Hg, Pb) were measured using ICP OES and ICP-MS after acid digestion. All detected levels fell below recommended daily intake values and permitted limits for toxic heavy metals, indicating that ayahuasca is safe for oral administration regarding total elemental content.
Journal of psychopharmacology (Oxford, England)
June 28, 2025
Rafael S Rodrigues, Isabel Wießner, Dimitri Daldegan-Bueno et al.
6 citations
Two scales that measure altered states of consciousness—the OAV and the 5D-ASC—were adapted and validated for Brazilian Portuguese through expert review and back-translation. In an online survey of 3762 people recounting their psychedelic experiences, factor analyses confirmed an 11-factor structure for the OAV and a 6-factor structure for the 5D-ASC, both with strong internal consistency (α > 0.76). Convergent validity was supported by significant correlations with the Mystical Experience Questionnaire and Ego Dissolution Inventory. Factor scores differed by substance, setting, and meditation frequency; ayahuasca and DMT experiences produced higher oceanic boundlessness and anxious ego-dissolution scores. The scales show reliable psychometric properties for Brazil, though sample homogeneity and recall bias are limitations.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2023
Isabel Wießner, Marcelo Falchi, Dimitri Daldegan-Bueno et al.
6 citations
Low to moderate doses of LSD alter language structure, semantics, and vocabulary over time. In a double-blind, placebo-controlled crossover study, 24 healthy volunteers (age 35±11, 33% women) received 50 μg LSD or placebo. LSD reduced verbosity, lexicon, and connectivity in speech networks from 1.5 to 4 hours, decreased semantic distances between words from 2 to 24 hours, and shifted vocabulary related to grammar, persons, time, space, and biological processes from 1.5 to 24 hours. Simpler, disconnected structure and increased semantic similarity may reflect cognitive impairments, while vocabulary changes may indicate subjective perceptual shifts. Automated language analysis could offer unconstrained insights into psychedelic cognition.
Journal of Psychoactive Drugs
September 17, 2021
Dimitri Daldegan‐bueno, Vanessa Manchim Favaro, Luís Fernando Tófoli et al.
6 citations
A reproducible five-day protocol for freeze-drying ayahuasca produces a stable extract with alkaloid concentrations similar to the original liquid. From two liters of ayahuasca, approximately 295 grams of freeze-dried extract were obtained, with a dry matter content of 14.75%. The freeze-dried extract retained its texture quality after three years of storage in a vacuum desiccator at about 6°C. The protocol includes alkaloid quantification by liquid chromatography-tandem mass spectrometry for both liquid and freeze-dried forms. Further research is needed on the effects of storage conditions and lyophilization on alkaloid quantities, particularly the impact of heat on β-carbolines.
Journal of psychoactive drugs
November 23, 2024
Daniel Perkins, Jerome Sarris, Tessa Cowley-Court et al.
5 citations
People who consume ayahuasca in naturalistic settings—religious, traditional, or non-traditional—report better current mental health and greater psychological well-being, according to a large online survey of 7,576 participants from over 50 countries. More lifetime ayahuasca uses were linked to better mental health scores, and this association remained strong even after accounting for other factors and did not fade over time. Strong mystical experiences, self-insights, and community or social support were also tied to better mental health and well-being, whereas acute extreme fear during sessions and difficulty integrating the experience were linked to poorer outcomes. These patterns held for individuals both with and without a history of mental illness.
Trends in Psychiatry and Psychotherapy
October 18, 2022
Bheatrix Bienemann, Mariana Ridolfi, Marco Multedo et al.
5 citations
A validated scale for measuring ego dissolution demonstrated strong psychometric properties, though its factor structure may differ from the English version. Because validation is an ongoing process, further studies should compare ego dissolution scores across different substances and regions of the country.
January 1, 2021
Mauricio Diament, Bruno Ramos Gomes, Luís Fernando Tófoli
5 citations
Ayahuasca, a psychedelic brew, significantly enhances experiential learning and psychological insights. In a study involving 100 participants, 75% reported profound vision experiences that led to lasting personal growth. Participants engaged in meditation and therapy sessions post-experience, with 85% noting improved emotional well-being. The biochemical analysis revealed key alkaloids responsible for these effects. Psychotherapists integrating psychedelics into treatment plans observed a 60% increase in client engagement and understanding. These findings highlight the potential of ayahuasca in therapeutic settings, blending ancient practices with modern psychology.
International Journal of Drug Policy
September 2, 2025
Alexandra Wojdyslawski Nigri, Ilana Falcão de Arruda, Catarina Maia et al.
3 citations
A scoping review of 75 studies on psychedelics for substance use disorders found that most did not adequately account for sex or gender. Only 18 studies had sex-balanced samples, 46 underrepresented females, 9 included no females, and 5 did not report sex. Thirteen studies considered sex in their design, 11 conducted sex-based analyses of substance use outcomes, and only 5 acknowledged sex underrepresentation as a limitation. None addressed sex or gender in the discussion. The authors conclude that, given the recognized role of sex and gender in substance use disorder treatment, such explorations should be encouraged.
Discover mental health
April 8, 2025
Isabel Wießner, Júlia Paula Souza, Marcelo Demarzo et al.
3 citations
Mindfulness training may reduce aberrant salience—the exaggerated significance attributed to perceived elements linked to psychotic experiences—while improving attention and well-being. In a pilot study of 21 adults completing an 8-week Mindfulness-Based Health Promotion course, mindful attention and decentering increased from before the course to after and at three months post-course. Aberrant salience showed mixed changes: a factor called Heightened Cognition increased immediately after the course, while Heightened Emotionality and total aberrant salience decreased later. Greater increases in mindful attention correlated with greater decreases in Heightened Emotionality. Qualitative reports indicated improved stress management and daily integration of mindfulness practices. The findings suggest mindfulness can modulate attentional processes and reduce aberrant salience, offering a potential pathway for interventions in psychosis.
Journal of psychoactive drugs
January 1, 2025
Ana Cláudia Mesquita Garcia, Lucas Oliveira Maia, Everson Meireles et al.
3 citations
The Spiritual Well-Being Scale (SWBS) is a valid and reliable tool for Brazilian samples, measuring two factors: religious well-being (RWB) and existential well-being (EWB). The RWB factor showed superior psychometric performance, including better group differentiation and internal consistency. A U-shaped association emerged between psychedelic use and spiritual well-being: people who never used psychedelics reported the highest RWB and EWB scores, followed by frequent users, while occasional users scored lower. This pattern highlights the need for more research on the complex relationship between psychedelics and spiritual well-being.
Scientific reports
November 10, 2023
Lucas Cruz, Bheatrix Bienemann, Fernanda Palhano-Fontes et al.
3 citations
Ayahuasca, a psychoactive brew used as an entheogen for centuries, is being investigated as a treatment for clinical disorders. This study analyzed open-ended descriptions from nine people with treatment-resistant depression and twenty healthy controls after their first ayahuasca experience. Using quantitative textual analysis, five clusters emerged: altered consciousness, cognitive changes, somatic alterations, auditory experiences, and visual content. People with depression reported more aversive bodily reactions. The findings align with known psychedelic experience patterns and may guide therapeutic use of ayahuasca.
Anthropology of Consciousness
July 8, 2022
Bruno Ramos Gomes, Luís Fernando Tófoli
2 citations
Ibogaine, a non-typical psychedelic derived from the African plant Tabernanthe iboga, is used in four Brazilian addiction treatment clinics. Qualitative interviews with professionals and patients reveal variation in patient screening, preparation, ibogaine dosing, and post-treatment care. These practices are shaped by three contexts: the addiction treatment clinic market, Brazilian urban religious ayahuasca use, and the medical ibogaine protocol developed by Howard Lotsof. The study describes how ibogaine is understood and applied for addiction and depression treatment, highlighting contextual influences on treatment approaches.
PLOS mental health
January 1, 2025
Óscar Andión, José Carlos Bouso, Jerome J Sarris et al.
1 citation
Ayahuasca, a traditional Amazonian decoction, is being studied for mental health benefits, but its adverse effects are not well understood. An analysis of 10,836 participants from the Global Ayahuasca Survey found that 14.2% had a prior anxiety disorder and 19.7% a depressive disorder, yet their median mental health score (SF-12) was 50.16, comparable to the general population. A history of anxiety or depression was linked to more adverse mental states after use. However, experiences like visual distortions and higher ayahuasca use correlated with better mental health. Women reported more adverse states but no worsened mental health.
The International journal on drug policy
November 1, 2024
Rodolfo Olivieri, Luís Fernando Tófoli
1 citation
In mid-20th century Argentina, psychoanalysts Luisa de Álvarez de Toledo, Alberto Tallaferro, and Alberto Fontana combined psychoanalytic therapy with psychedelic substances such as LSD. Their clinical work suggested that psychedelics could enhance transference, trigger catharsis, and bypass unconscious defenses, enabling vivid exploration of patients' psyches that required interpretation. Resistance from the Argentine Psychoanalytic Association eventually ended this research. The essay argues that renewed dialogue about psychedelics in contemporary therapeutic practice is warranted, highlighting an overlooked chapter in psychoanalysis and urging engagement with emerging research.
Frontiers in psychiatry
January 1, 2023
Simon G D Ruffell, Nige Netzband, WaiFung Tsang et al.
1 citation
correction
This is a correction notice for a previously published article. It provides no new findings, arguments, or data.
Journal of psychoactive drugs
May 19, 2026
Ana Cláudia Mesquita Garcia, Lucas Oliveira Maia, Everson Meireles et al.
A Brazilian Portuguese version of the Psychedelic Integration Scales (PIS-BR) was validated in a cross-sectional online survey of 1,379 participants. The scale showed a unidimensional structure, high internal consistency (α = 0.95), and strong associations with mystical experience (r = 0.636) and positivity (r = 0.352). Qualitative analysis of open-ended responses revealed diverse integration strategies such as personal reflection, psychotherapy, spiritual practices, connection with nature, social sharing, and personal transformation, alongside reported difficulties. The findings support the PIS-BR as a valid measure for studying psychedelic integration in Brazil and highlight cultural variability in integration processes beyond acute drug effects.
Journal of religion and health
March 31, 2026
Ana Cláudia Mesquita Garcia, Everson Meireles, Eliza Mara Das Chagas Paiva et al.
A Brazilian Portuguese version of the Mystical Orientation Scale Revised (MOSR-BR) was developed and tested in 505 Brazilian adults. The scale showed a single underlying factor explaining 47.6% of the variance, with very high internal consistency. Higher mystical orientation scores correlated with greater death transcendence and with religious and existential well-being. People who used psychedelic substances occasionally or frequently scored higher on mystical orientation than non-users. The authors note the study is exploratory and limited by its cross-sectional design, non-random sampling, and lack of confirmatory factor analysis or test-retest reliability.
Research Square (Research Square)
August 23, 2023
Lucas Villar Magalhães da Cruz, Bheatrix Bienemann Favero, Fernanda Palhano-Fontes et al.
First-time ayahuasca users with treatment-resistant depression and healthy controls described their subjective experiences in open-ended questions. Textual analysis of responses from nine depressed and 20 healthy individuals revealed five clusters: altered consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Depressed participants reported more aversive bodily reactions, suggesting specific experiential features in depression. The results align with prior psychedelic research and may guide therapeutic applications of ayahuasca.
Psychopharmacology (Berl)
February 18, 2022
Dimitri Daldegan-Bueno, Lucas Oliveira Maia, Carolina Marcolino Massarentti et al.
Among people who reported quitting or reducing smoking after drinking ayahuasca, those who had a stronger mystical experience and took ayahuasca more frequently were more likely to quit entirely rather than just reduce or relapse. Positive mood during the experience was associated with a higher risk of relapse. The findings suggest that ayahuasca may help with smoking cessation, possibly through mystical-type experiences.
Revista dos Trabalhos de Iniciação Científica da UNICAMP
December 13, 2018
Carolina Marcolino Massarentti, Luís Fernando Tófoli, Lucas Oliveira Maia et al.
Ayahuasca, a psychedelic used in ritual contexts and by Brazilian syncretic religions, may help reduce or stop tobacco smoking. In a survey of 451 people who used ayahuasca, 78% (351) reported not currently smoking. Most participants (89%, 400) attended ayahuasca sessions without the specific intention to quit smoking; their motivations were self-knowledge, spiritual concerns, healing, or curiosity. The reduction or cessation of smoking appeared as an unintended consequence, suggesting that ayahuasca experiences can contribute to changes in addictive behaviors.
The Plant journal : for cell and molecular biology
July 1, 2025
Taynara Simão Matos, Camila Dias Lourenço Dos Santos, Luís Fernando Tófoli et al.
The specialized metabolite profile in Psychotria viridis leaves, a plant used in ayahuasca preparation, varies with growing conditions and seasonality. Flavonoids were the main compounds differentiating seasonal samples. Energy-related pathways—ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and the citrate cycle—showed significant seasonal variation. Flavonoid, flavone, and flavonol biosynthesis differed between plants grown in full sunlight versus shade, suggesting a response to oxidative stress. DMT concentrations did not significantly change across conditions.