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.
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.