British journal of pharmacology
June 1, 2024
Isabel Werle, Laura M M Nascimento, Aymee L A Dos Santos et al.
21 citations
A single oral dose of ayahuasca containing 0.3 mg/kg of DMT increased within-session extinction of contextual freezing behavior in rats without affecting recall; two consecutive daily doses enhanced extinction recall. These effects occurred for both 1- and 21-day-old memories in males and females, independent of changes in anxiety or general exploratory activity. Blocking 5-HT2A receptors in the infralimbic cortex prevented within-session extinction, while blocking 5-HT1A receptors prevented between-session extinction. The findings highlight complementary mechanisms by which ayahuasca facilitates behavioral suppression of aversive memories, suggesting potential benefits for stress-related disorders.
Neuroscience & Biobehavioral Reviews
September 20, 2024
Isabel Werle, Leandro J. Bertoglio
17 citations
Threatening events can create maladaptive memories that existing treatments often fail to address. This review of nearly 400 studies since 1957 examined how various psychedelics—including psilocybin, LSD, DMT, mescaline, 5-MeO-DMT, DOI, and MDMA—affect aversive memory extinction, reconsolidation, learned fear, anxiety, and locomotion in rodents. Psychedelics frequently show biphasic effects on locomotion at doses that enhance extinction learning, impair memory reconsolidation, or reduce learned fear and anxiety. Emerging evidence suggests a dissociation between prospective benefits and locomotor effects. Under-explored aspects include sex differences, memory age and generalization, repeated treatments, and timing of changes. Validating findings in traumatic-like memory models is essential for improving therapeutic approaches.
Acta Neuropsychiatrica
January 1, 2025
Isabel Werle, Marina A. M. Portes, Leandro J. Bertoglio
2 citations
Psychedelic-assisted therapies show promise for treating depression, anxiety, PTSD, and substance use disorder, with lasting effects after few applications. Athletes, who face high stress and pressure, are susceptible to these conditions, but the impact of psychedelics on athletic performance is largely unknown. Preclinical studies indicate that psilocybin, LSD, DMT, and ayahuasca have anti-inflammatory and anti-nociceptive properties. Research on classical psychedelics or MDMA affecting muscle strength, motor coordination, locomotion, endurance, fluid balance, hormonal regulation, and metabolism is scarce. Further animal and human studies are needed to address these gaps and explore potential benefits.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2026
Isabel Werle, Francisco S Guimarães, Rafael G Dos Santos et al.
Ayahuasca, a brew containing the psychedelic DMT, helps rodents overcome persistent and generalized fear memories by boosting brain-derived neurotrophic factor (BDNF) signaling in the infralimbic (IL) region of the medial prefrontal cortex. In rats exposed to stress or high-intensity fear conditioning, repeated ayahuasca (0.3 mg/kg DMT) enhanced extinction learning and its retention, and reduced fear generalization. These effects were blocked by infusing an anti-BDNF antibody or a TrkB receptor antagonist into the IL cortex. The reduction in fear generalization depended on BDNF in females but not males. The findings suggest psychedelics may aid in treating difficult-to-extinguish trauma memories, such as those in PTSD.