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.
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.