The kappa opioid receptor and the sleep of reason: Cortico-subcortical imbalance following salvinorin-A.

Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in multimodal EEG, SPECT, and subjective effects following the acute administration of salvinorin-A are reported. The study included two sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. Results The EEG measures showed a marked increase in delta and gamma waves, and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding SPECT measures, significant decreases in regional cerebral blood flow (rCBF) were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant rCBF increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs, but with an evidently dissociative nature. No dysphoric effects were reported. Conclusion The salvinorin-A-mediated KOR agonism induced dramatic psychotomimetic effects, along with a generalized decrease in CBF and electric activity within the cerebral cortex..