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.
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.
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.
Substance Use & Misuse
April 25, 2022
Dimitri Daldegan-Bueno, Dóra Révész, Paulo Rogério Morais et al.
15 citations
Regular ceremonial use of ayahuasca is associated with lower anxiety, less negative affect, higher intrinsic religiosity, and reduced past-month use of both licit and illicit substances compared to non-regular use. Regular users also reported lower general and physical quality of life. The study compared 101 regular users with 185 non-regular users in Brazil, finding no differences in lifetime drug use between groups after adjusting for sociodemographic factors.
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.
Behavioural Brain Research
April 1, 2022
Dimitri Daldegan-Bueno, Vanessa Manchim Favaro, Paulo Rogério Morais et al.
10 citations
Repeated daily ayahuasca administration over 30 days in male Wistar rats produced dose-dependent behavioral effects: a low dose (120 mg/kg) increased ambulation, while a very high dose (3600 mg/kg) decreased vertical exploration and reduced weight gain. The highest dose also increased c-Fos expression in the hippocampus and infralimbic cortex, indicating heightened neural activation in emotional processing and serotonergic pathways. The study does not support an anxiolytic effect of repeated ayahuasca in a novel anxiogenic environment but suggests low doses warrant further investigation. The absence of severe behavioral impairment reinforces ayahuasca's safety profile.
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.
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.
Neuropharmacology
November 5, 2025
Dimitri Daldegan-Bueno, C Donegan, Rachael Sumner et al.
4 citations
In an open-label phase 2A trial, 19 participants with major depressive disorder, most of whom were taking antidepressants, took microdoses of LSD twice weekly for eight weeks. No serious adverse events occurred, and one participant withdrew due to anxiety. Depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by 59.5% at the end of the intervention, with improvements sustained for up to six months. Anxiety, rumination, stress, and quality of life also improved. The results provide preliminary evidence that microdosed LSD is safe and feasible for treating moderate depression, but randomized controlled trials are needed.
August 4, 2022
Dimitri Daldegan-Bueno, Natalia Maria Simionato, Vanessa Manchim Favaro et al.
4 citations
preprint
A systematic review of 32 animal studies (rodents, primates, and zebrafish) on ayahuasca, a psychedelic brew, found that at doses similar to ceremonial use it is safe, but toxic at high doses. Behavioral results suggest antidepressant effects and a potential to reduce the rewarding effects of ethanol and amphetamine-type drugs, while anxiety-related outcomes remain inconclusive. Ayahuasca also influences locomotor activity, so controlling for movement is important in behavioral tasks. Neurobiologically, ayahuasca affects brain structures involved in memory, emotion, and learning, and its effects involve pathways beyond the serotonergic system. Key gaps in ayahuasca research can still be addressed using animal models.
Brain Behavior and Immunity Integrative
September 14, 2024
Bianca Castro Dos Santos, Ana Kéren Gomes Reis, Ricardo Aparecido Baptista Nucci et al.
1 citation
Neuropathic pain, a chronic condition often accompanied by depression, is difficult to treat with conventional medications. Ayahuasca, a psychedelic brew from Amazonian plants, shows promise for modulating pain. Preclinical studies and fMRI analyses suggest it reduces activity in the default mode network, which is linked to depression, and activates serotonin and sigma-1 receptors while modulating immune responses, including glial cells and the midbrain periaqueductal gray. These actions may address both pain and mood disturbances. However, rigorous research is needed to establish its efficacy, safety, mechanisms, and long-term effects.
Ther Adv Psychopharmacol
December 4, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.
People with depression who microdosed LSD described their experiences in interviews from an open-label trial. The analysis identified themes such as improved mood, increased energy, and greater emotional openness, though some participants also reported anxiety or discomfort. The findings suggest that microdosing may offer benefits for some individuals, but the open-label design means results should be interpreted cautiously.
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.