Anesthesiology
February 21, 2022
Erik Olofsen, Jasper Kamp, Thomas K. Henthorn et al.
33 citations
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.
ACS pharmacology & translational science
July 12, 2024
Albert Dahan, Simone Jansen, Rutger van der Schrier et al.
8 citations
The anesthetic, analgesic, and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.
Anesthesiology
September 12, 2022
Albert Dahan, Erik Olofsen, Thomas K. Henthorn et al.
3 citations
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.
British journal of clinical pharmacology
June 24, 2026
Catherine M K E De Cuba, Annika A De Goede, Joost C Van Mechelen et al.
A single intravenous dose of S-ketamine produced acute and delayed effects on brain activity and motor cortex excitability that lasted up to seven days in 16 healthy adults. Intravenous S-ketamine reduced motor-evoked potential amplitude acutely and caused a sustained weakening of long-interval intracortical inhibition, which followed a linear relationship with drug concentration. Transcranial magnetic stimulation combined with electroencephalography showed acute changes in brain electrical activity across all treatments, but delayed changes only after intravenous and high-dose oral S-ketamine. Electroencephalography revealed acute decreases in alpha, beta, and delta power with eyes closed, and sustained increases in delta power with eyes open, the latter also showing a linear concentration-effect relationship. These delayed pharmacodynamic effects are distinct from acute effects and may help explain S-ketamine's antidepressant action.