Ketamine produces both pain relief (analgesia) and psychedelic effects, and these two effects are linked, possibly because dissociation generates analgesia. In healthy male volunteers receiving escalating doses of S-ketamine and racemic ketamine, the concentration-effect relationship and the speed of onset and offset were the same for both antinociception and altered external perception. S-ketamine had a potency (C50) of 0.51 nmol/ml and a blood-effect site equilibration half-life of 8.3 minutes. R-ketamine did not contribute to either effect, while S-norketamine had a small antagonistic effect. The authors suggest further studies are needed to explore brain connectivity underlying these effects.
The authors respond to a critique about how to describe mind-altering drugs like ketamine, psilocybin, and cannabis. They argue that terms like "dissociative" are inadequate because these drugs produce diverse symptoms beyond disconnection from reality. They propose "psychoplastogen" as a better term, focusing on the shared mechanism of promoting rapid neural plasticity and rewiring of brain circuits, which underlies therapeutic effects such as antidepressant and pain relief actions. This term avoids the limitations of describing subjective experiences and instead highlights the neurobiological mechanism responsible for healing.