Ketamine is metabolized into several compounds, and this study shows that norketamine is not the main metabolite circulating in the blood after a single 40-minute infusion of 0.5 mg/kg ketamine in patients with treatment-resistant bipolar depression. Instead, dehydronorketamine was the major metabolite in four out of nine patients, norketamine in three, and hydroxynorketamine in two. Large inter-patient variation in metabolite levels was observed. The findings suggest that future research on ketamine's effects should measure these downstream metabolites.
A new computer model describes how the drug harmaline, which inhibits the enzyme monoamine oxidase A, alters body temperature in mice when combined with the serotonin receptor agonist 5-MeO-DMT. Harmaline causes hypothermia by activating 5-HT1A receptors, while 5-MeO-DMT triggers hyperthermia by stimulating 5-HT2A receptors. The model successfully separates drug-induced fever from stress-induced fever caused by handling and injection. When harmaline is given alongside 5-MeO-DMT, the concentration of 5-MeO-DMT needed to produce hyperthermia drops fourfold, showing a quantitative interaction. Dangerous overheating from toxic doses is linked to increased harmaline exposure, not 5-MeO-DMT. This framework may help predict how serotonergic drugs and stress affect thermoregulation.