Effects of ketamine enantiomers on morphine and THC subjective effects in rats.
Journal of psychopharmacology (Oxford, England) December 26, 2025 Natalia Malikowska-Racia, Joanna Gołębiowska, Katarzyna Starowicz et al.
Ketamine isoforms (R-, S-, and racemic R,S-) do not produce opioid- or cannabis-like subjective effects and are unlikely to fully mask the interoceptive effects of morphine or THC. In rats trained to discriminate morphine or THC from vehicle, none of the ketamine isoforms fully blocked the discriminative stimulus effects of morphine or THC, nor did they fully substitute for either drug. Ketamine isoforms did not alter response rates in the morphine experiment but suppressed responding in the THC experiment, suggesting coadministration with cannabinoids may lead to pronounced sedative-like suppression. These findings warrant further investigation into the safety and interaction profiles of such drug combinations.