Frontiers in Neuroscience
April 17, 2023
Marvin M. Urban, Moritz R. Stingl, Marcus W. Meinhardt
47 citations
Since the 1960s, psychedelics have shown potential for persistently treating substance use disorders, but the biological mechanisms behind their therapeutic effects remain unclear. Serotonergic hallucinogens are known to alter gene expression and neuroplasticity, especially in prefrontal brain regions, yet how these changes specifically counteract the neuronal circuit alterations that develop during addiction is largely unknown. This narrative mini-review synthesizes established addiction research with findings and theories on the neurobiological effects of psychedelics, providing an overview of potential mechanisms underlying treatment of substance use disorders with classical hallucinogens and identifying gaps in current understanding.
Research Square
March 31, 2026
Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.
A compound derived from ibogaine, oxa-noribogaine, reduces alcohol consumption in rats by strengthening learning from negative drinking outcomes. It produces sustained decreases in alcohol intake and relapse-like drinking, matching or exceeding ibogaine's efficacy without detectable motor or cardiac side effects. These effects involve transient changes in prefrontal brain activity, lasting alterations in glutamatergic signaling after aversion-related learning, and normalization of neurotrophic signaling in cortico-striatal circuits. The results generalize across multiple models, genetically diverse animals, and independent study sites, identifying oxa-noribogaine as a promising treatment candidate for alcohol use disorder.
July 18, 2025
Marvin M. Urban, Eric Zillich, Nathalie M. Rieser et al.
preprint
A single dose of psilocybin (25 mg) was associated with changes in DNA methylation in patients with alcohol use disorder. One methylation site in the TLE4 gene and a region in the RASGRP4 gene showed significant alterations. Co-methylation networks linked to psilocybin treatment were also associated with reduced depressive symptoms and drinking behavior, and involved genes related to neuroplasticity and immune function. Baseline methylation differences between treatment responders and non-responders appeared in genes related to synaptic plasticity and neurotransmitter systems. The findings are preliminary due to the small sample size but align with prior research and suggest possible biological pathways for psilocybin's therapeutic effects.