Journal of Neuroscience
January 19, 2005
Dao‐yao He, Nancy N. H. Mcgough, Ajay Ravindranathan et al.
181 citations
Ibogaine, a natural alkaloid with side effects that prevent clinical use, reduces alcohol consumption in rats. In two-bottle choice and operant self-administration tests, ibogaine decreased ethanol intake and also reduced relapse-like drinking. The effect is mediated by glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA): ibogaine microinjected into the VTA reduced self-administration, systemic ibogaine increased GDNF expression in the midbrain, and in dopaminergic SHSY5Y cells ibogaine activated the GDNF pathway (phosphorylation of Ret and ERK1). Intra-VTA GDNF mimicked ibogaine's effect, while anti-GDNF antibodies blocked it. GDNF in the VTA therefore mediates ibogaine's action on ethanol consumption, suggesting GDNF as a target for alcoholism medications that could avoid ibogaine's side effects.
Science Advances
November 17, 2021
Marcus W. Meinhardt, Simone Pfarr, Grégory Fouquet et al.
92 citations
Psilocybin restores deficits in the metabotropic glutamate receptor 2 (mGluR2) caused by alcohol, which leads to the reversal of pathological behaviors associated with alcoholism.
Brain
May 4, 2024
Jérôme Jeanblanc, Romain Bordy, Grégory Fouquet et al.
10 citations
Psilocybin reduces alcohol self-administration in rats by 50% when injected 4 hours before a drinking session, either intraperitoneally (1 mg/kg) or directly into the left nucleus accumbens (0.15 μg), but not the right nucleus accumbens or left ventral tegmental area. The effect is blocked by a 5-HT2A receptor antagonist injected into the left nucleus accumbens. Psilocybin increases dopamine D2 receptor mRNA in the nucleus accumbens and prefrontal cortex of rats that self-administered alcohol, but not saccharin, and increases D1 receptor mRNA only in the prefrontal cortex. These findings suggest psilocybin acts through the 5-HT2A receptor in the left nucleus accumbens, potentially via increased D2 receptor expression, and reveal unexpected hemispheric lateralization of psychedelic effects.
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.
Biologie aujourd'hui
January 1, 2023
Fahd Hilal, Jérôme Jeanblanc, Mickaël Naassila
3 citations
Ketamine, an atypical psychedelic used for major depression, shows promise for treating alcohol use disorder (AUD) by reducing withdrawal symptoms and alcohol craving. Preclinical and clinical studies indicate its antidepressant properties contribute to lower relapse likelihood, especially in ketamine-assisted psychotherapies. Effectiveness is linked to regulating glutamatergic pathways, enhancing neuroplasticity, and rewiring brain connectivity. However, sex differences in responses and the roles of ketamine metabolites require further investigation. Current research also examines ketamine addiction and the comorbidity of alcohol addiction and depression, which is more frequent in females.
July 12, 2026
Fahd François Hilal, Méléna Dreinaza, Quentin Lebel et al.
S-ketamine, but not R-ketamine, dose-dependently suppresses binge-like alcohol self-administration in male rats, with the strongest effect at 40 mg/kg. This suppression is selective, occurring without sedation or motor impairment, and is most pronounced on front-loaded drinking. However, the effect rapidly diminishes with repeated doses, indicating rapid tolerance. R-ketamine does not alter alcohol intake under the same conditions, nor does prior R-ketamine exposure affect subsequent S-ketamine efficacy. The findings suggest that stereochemistry, dosing schedule, and alcohol exposure pattern are key determinants of ketamine's potential for treating alcohol use disorder.