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.
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.
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 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
November 5, 2025
Dimitri Daldegan‐bueno, C Donegan, Rachael L. 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.