Neuropsychopharmacology
May 5, 2020
Marcus W. Meinhardt, Cansu Güngör, Ivan Skorodumov et al.
66 citations
Psychedelic-assisted psychotherapy is hypothesized to restore normal brain function in people with alcohol use disorder (AUD) and reduce relapse risk after a single session. In this study, three treatment schedules with psilocybin or LSD were tested in male and female rats using the alcohol deprivation effect (ADE) model of relapse-like drinking. Neither high doses comparable to clinical studies nor chronic microdosing produced long-lasting reductions in relapse-like drinking. Only sub-chronic psilocybin had a short-lasting anti-relapse effect, but this regimen is not considered a translatable treatment. The findings do not support the hypothesis that microdosing or high-dose psychedelics reduce relapse behavior in this model, though the authors note that animal models may not fully capture psychedelics' therapeutic potential.
Translational Psychiatry
December 14, 2023
Ivan Skorodumov, Rainer Spanagel, Jonathan Reinwald et al.
25 citations
Psilocybin, a psychedelic compound, may help treat alcohol use disorder (AUD), but its brain effects in AUD are not well understood. In a placebo-controlled crossover study with healthy rats and a rat model of alcohol relapse, psilocybin broadly decreased functional connectivity across the brain while increasing connectivity between serotonin-related core regions and cortical areas. It also reduced connectivity within the default mode network (DMN), mirroring human findings. However, in rats with a history of alcohol relapse, this DMN hypoconnectivity was blunted, and the blunting correlated with relapse intensity. The results suggest that a standard psilocybin dose may be insufficient for severe AUD, a consideration for future clinical trials.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Marcus W Meinhardt, Ivan Skorodumov, Jérôme Jeanblanc et al.
8 citations
A new approach in psychiatric drug development, the preclinical randomized controlled trial (preRCT), was tested across three European centers using a rat model of alcohol relapse. Ketamine (20 mg/kg) reduced relapse, while R-ketamine worked only in females at the same dose; a higher dose (40 mg/kg) was effective in males. The sex-dependent effects were linked to plasma R-ketamine levels, which were twice as high in females. R-ketamine produced a lasting reduction in alcohol consumption without adverse effects. The findings support moving to a clinical trial that accounts for sex differences.
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.