Psychotomimesis Mediated by κ Opiate Receptors

TLDR

Kappa opioid agonists act as analgesics without typical morphine side effects, but their dysphoric effects, such as those seen with cyclazocine, are thought to involve sigma‑phencyclidine receptors. The benzomorphan kappa agonist MR 2033, inactive at sigma‑phencyclidine receptors, produced dose‑dependent dysphoric and psychotomimetic effects in male subjects via kappa opioid receptors, as shown by naloxone antagonism, suggesting opposing opioid systems modulate emotional and perceptual experiences.

Abstract

The kappa opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the kappa agonist cyclazocine are thought to be mediated by an action at sigma-phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at sigma-phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, kappa opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of mu agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.