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.
Journal of neural transmission (Vienna, Austria : 1996)
May 1, 2024
Fahd François Hilal, Jerome Jeanblanc, Chloé Deschamps et al.
8 citations
A review of preclinical studies in animal models examines two emerging approaches for alcohol use disorder: psychedelics and epigenetic drugs (epidrugs). Both treatments show potential benefits for reducing alcohol drinking, seeking, motivation, and relapse. Because psychedelics and epidrugs may share common and complementary mechanisms of action, there is an opportunity for exploring synergies between these approaches and their parallel effectiveness in treating AUD and associated psychiatric conditions.
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.