Progress in neuro-psychopharmacology & biological psychiatry
December 20, 2024
Guilherme Lodetti, Rafael Mariano de Bitencourt, Eduardo Pacheco Rico
9 citations
Alcohol is a harmful drug, and dependence on it is often resistant to treatment, with no completely effective model available. Classic psychedelics like LSD, psilocybin, and ayahuasca have shown promising pharmacotherapeutic effects in treating treatment-resistant conditions, including addiction, particularly alcohol dependence. This narrative review examines emerging research on psychedelics for alcohol use disorder treatment. These substances may treat addiction by modulating neuroplasticity in the brain. Since serotonergic psychedelics do not produce physical dependence or withdrawal symptoms with repeated use, they are considered promising treatment options. However, great inter-individual variability exists in the duration of effects, and further studies using different doses and protocols are needed.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
July 1, 2026
Guilherme Lodetti, Rafael Mariano de Bitencourt, Antonio Inserra et al.
A single dose of Ayahuasca reduced relapse-like alcohol drinking in alcohol-dependent rats, with effects varying by sex and alcohol concentration. It also lessened anxiety- and depression-like behaviors caused by alcohol withdrawal, increased dopamine in the striatum of both male and female rats, and restored serotonin levels in the cortex primarily in males. Ayahuasca partially reversed alcohol-related drops in brain-derived neurotrophic factor and reduced markers of oxidative stress in the frontal cortex, hippocampus, and striatum. However, antioxidant enzyme activities were not consistently altered, and some neurochemical and oxidative stress measures showed only partial normalization. The findings suggest Ayahuasca modulates multiple neurobiological pathways disrupted by chronic alcohol exposure, with region- and sex-dependent effects.
Psychopharmacology
April 14, 2026
Guilherme Lodetti, Antonio Inserra, Henrique Redivo et al.
A single exposure to ayahuasca reversed behavioral and biochemical changes caused by 14 days of unpredictable chronic stress in adult zebrafish. Stressed fish showed impaired sociability, anxiety-like behavior, hyperactivity, elevated whole-body cortisol, and reduced whole-brain BDNF. Ayahuasca restored sociability, reduced anxiety-like behavior and hyperactivity, normalized cortisol levels, and increased BDNF. These findings suggest ayahuasca can reverse stress-induced behavioral and neuroendocrine alterations, supporting further clinical studies for chronic stress.
Neuroscience
January 22, 2026
Guilherme Lodetti, Gislaine Zilli Réus, Eduardo Pacheco Rico
Fewer than half of patients with major depressive disorder achieve remission with standard pharmacotherapy, and many cannot tolerate it. This narrative review examines classic psychedelics as an alternative treatment. These substances primarily bind to 5-HT2A receptors, increasing connectivity between sensory and motor brain networks. They generate long-term behavioral responses comparable to traditional antidepressants. Clinical and experimental studies show that classic psychedelics alleviate depressive symptoms. The mood improvement is thought to stem from effects on neuroplasticity, including neurogenesis and related signaling pathways.