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.
Pilot and feasibility studies
October 5, 2023
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.
23 citations
An estimated 260 million people worldwide have depression, and many self-treat with microdoses of psychedelics like LSD and psilocybin despite limited clinical evidence. A prior phase 1 study in healthy volunteers found LSD microdosing safe, well tolerated, and feasible with good adherence. This open-label pilot trial (LSDDEP1) will test tolerability and feasibility of an 8-week LSD microdosing regimen in 20 patients with major depressive disorder. Participants receive a sublingual LSD formulation (MB-22001) twice weekly at 5–15 µg. Tolerability is measured by withdrawal due to adverse events; feasibility by clinic visit attendance. Antidepressant response will be assessed with MADRS scores over 8 weeks. Results will inform a future randomized controlled trial.
Progress in neuro-psychopharmacology & biological psychiatry
July 13, 2023
Dimitri Daldegan-Bueno, Natalia Maria Simionato, Vanessa Manchim Favaro et al.
18 citations
Ayahuasca, a psychedelic brew, is being studied for therapeutic uses. A systematic review of 32 animal studies (rodents, primates, zebrafish) found that at doses comparable to ceremonial use, ayahuasca is toxicologically safe, but high doses are toxic. Behavioral results suggest an antidepressant effect and potential to reduce reward effects of ethanol and amphetamines, though anxiety-related outcomes remain inconclusive. Ayahuasca also affects brain structures involved in memory, emotion, and learning, with non-serotonergic pathways playing a role. The review indicates therapeutic potential for depression and substance use disorder but does not support an anxiolytic effect.
Trials
August 24, 2024
Dimitri Daldegan-Bueno, Carina Joy Donegan, Anna Forsyth et al.
14 citations
A phase 2b randomized controlled trial will test whether repeated low doses of LSD (4 to 20 micrograms, taken twice weekly for 8 weeks at home) reduce depressive symptoms in people with major depressive disorder, compared to an active placebo. The trial is triple-blind and includes measures of mood, personality, sleep, brain activity, blood biomarkers, and safety. This is the first controlled trial to test microdosed LSD in patients' natural environment. Results will help determine whether psychedelic microdosing is a viable additional treatment for depression and guide future research.
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.
Neuropharmacology
December 1, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani et al.
4 citations
Before starting a low-dose LSD regimen, people with major depression held varied expectations shaped largely by media and personal experience. Over half had tried other treatments that failed. Many expected subtle effects or had no specific expectations, while some anticipated changes in consciousness or neural rewiring. Hope served both as a motivator and a buffer against disappointment. The findings underscore how media influences expectations and suggest that current expectancy measures miss important factors specific to psychedelic therapy.