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.
Experimental Neurology
June 1, 2022
I. Ornelas, F. A. Cini, Isabel Wießner et al.
37 citations
LSD treatment improved performance in a novel object recognition task in rats and a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. Simulations using a neural network model of a cortico-hippocampal circuit, with baseline plasticity strength as a proxy for age and increased plasticity related to LSD dose, fit the experimental data well. The results suggest that LSD has nootropic effects.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, Isabel Wießner et al.
35 citations
Vaporized DMT, a short-acting psychedelic, rapidly reduced depression symptoms in patients with treatment-resistant depression. In an open-label trial, 14 patients received inhaled DMT at 15 mg and then 60 mg. The treatment was safe and well-tolerated, with no serious adverse events. By day 7, depression scores on the Montgomery-Asberg Depression Rating Scale dropped by an average of 21.14 points. The response rate was 85.71%, and the remission rate was 57.14%, with effects lasting up to 3 months. Suicidal ideation also decreased significantly, with no severe ideation the day after dosing. Vaporized DMT offers a non-invasive, time-efficient alternative to longer-acting psychedelics and traditional antidepressants.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
March 1, 2024
Marcelo Falchi-Carvalho, Isabel Wießner, Sérgio Ruschi B Silva et al.
25 citations
Inhaled N,N-Dimethyltryptamine (DMT) produces dose-dependent increases in the intensity, positive valence, and perceptual effects of subjective experiences, with only mild, transient, and self-limited increases in blood pressure and heart rate. No changes in safety blood biomarkers or serious adverse events occurred. The acute effects last around 10 minutes, offering a potentially cost- and time-effective alternative to longer-acting oral psychedelics for clinical use in mood disorders. This open-label, single-ascending, fixed-order, dose-response study in 27 healthy volunteers tested five dose pairs (5/20 mg through 15/60 mg) of inhaled DMT (BMND01 candidate).
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.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2025
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
16 citations
Vaporized N,N-dimethyltryptamine (DMT) produced rapid and sustained antidepressant effects in a small open-label trial of six people with treatment-resistant depression. Depression severity, measured by the Montgomery-Asberg depression rating scale (MADRS) and Patient Health Questionnaire-9 (PHQ-9), decreased significantly from the first day through one month after dosing. The average MADRS score dropped by 22 points at day 7 and 17 points at one month. By day 7, 83.33% of patients responded to treatment and 66.67% achieved remission; at one month, 66.67% maintained response and 50% maintained remission. The short-acting, noninvasive vaporized route may improve accessibility to psychedelic treatments.
Journal of clinical medicine
June 6, 2023
Maria Eduarda Sodré, Isabel Wießner, Muna Irfan et al.
15 citations
Sleep is increasingly understood as a local brain phenomenon, not just a whole-brain process, with different states of consciousness—wakefulness, sleep onset, light sleep, deep sleep, and REM sleep—able to occur simultaneously, leading to dissociative states. These are classified as physiological (daydreaming, lucid dreaming, false awakenings), pathological (sleep paralysis, sleepwalking, REM sleep behavior disorder), and altered (hypnosis, anesthesia, psychedelics). The article reviews the neurophysiology and phenomenology of these states, concluding that their study is important for understanding consciousness and treating neuropsychiatric diseases.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
June 17, 2025
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde et al.
7 citations
Inhaled vaporized DMT (60 mg) produces profound altered states of consciousness and is safe and well-tolerated in healthy adults. In a randomized, double-blind, placebo-controlled crossover trial with 25 participants, DMT significantly increased subjective intensity and most measures on the 5D-ASC, HRS, and MEQ questionnaires compared to an active placebo (0.6 mg DMT). Physiological parameters such as blood pressure and heart rate rose transiently within safe limits. Adverse events were predominantly mild and temporary. Biochemical changes were not clinically relevant. Physiological increases correlated with subjective experiences, suggesting a link between bodily responses and the psychedelic state.
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.
medRxiv
January 4, 2024
Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont et al.
5 citations
preprint
A single-day session of vaporized DMT, a psychedelic compound found in ayahuasca, rapidly reduced depression symptoms in six patients with treatment-resistant depression. Depression scores on two standard rating scales dropped substantially by day one and remained lower for one month. By day seven, 83% of patients responded to treatment and 67% achieved remission; at one month, 67% maintained response and 50% maintained remission. The non-invasive, short-acting nature of DMT may make psychedelic treatments more accessible in interventional psychiatry.
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.
Progress in brain research
January 1, 2025
Handersson Barros, Marcelo Falchi-Carvalho, Lucas O Maia et al.
2 citations
Psychedelic experiences, particularly those from DMT, are often intense and hard to put into words, which complicates therapeutic integration. In a Phase I clinical trial, participants created mandalas as a nonverbal expressive tool. The mandalas helped them symbolically express subjective content that was difficult to verbalize, thereby supporting integration. Despite this promise, expressive tools remain underused in psychedelic clinical protocols. Including art may enhance therapeutic benefits by deepening understanding and meaning of the experience.
Journal of Psychopharmacology
July 8, 2026
Raynara Bolcont, Fernanda Palhano-Fontes, Handersson Barros et al.
Inhaled DMT, combined with psychological support, is associated with reduced state anxiety up to one day after administration in both healthy individuals and patients with treatment-resistant depression. Healthy volunteers reported increased life satisfaction up to 14 days. Patients showed increased life satisfaction after 12 months and sustained improvements in quality of life over that period, including physical health, psychological health, social relationships, and environment, as well as inner peace and hope and optimism. The study is limited by an open-label design, lack of placebo control, and modest sample size.
Journal of Psychopharmacology
December 4, 2025
Natan Silva-Costa, Jéssica Andrade Pessoa, Kátia Cristina Andrade et al.
Ayahuasca produces profound changes in perception, cognition, and emotion, including mystical experiences and altered mind-wandering, while decreasing global alpha brain oscillations and increasing frontomedial delta and right posterior theta and beta. Lower theta during the experience is linked to stronger mystical experiences, and higher alpha is associated with less thought about nothing. Baseline brain activity before taking ayahuasca can predict some subjective effects: lower baseline theta predicts stronger bodily awareness and interoception, and lower baseline beta predicts greater positive emotionality.