Salvinorin-A induces intense dissociative effects, blocking external sensory perception and modulating interoception and sense of body ownership in humans
Addy, P. H., Barker, S., Claramunt, J., Coimbra, J., Garrido, M., Gonzales, M., Johnson, M. W., Maqueda, A. E., Puntes, M., Riba, J., Valle, M.
This double-blind, randomised placebo-controlled, within-subjects study (n=8) investigated the effects of vaporized salvinorin-A (0.25, 0.50, & 1 mg) on interoception and the sense of body-ownership in healthy volunteers, who reported an increase of bodily sensations at moderate doses, and an almost complete loss of body ownership and out-of-body experiences at the highest. These effects were rapid and intense but short-lived and included perceptual modifications in the visual domain and commonly entailed auditory hallucinations that are not typical for serotonergic hallucinogens by contrast. This implicates that the Kappa opioid system plays a significant role in the regulation of sensory perception, interoception, and the sense of body ownership.
Abstract
Background: Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedeliclike changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception.Methods: A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness.Results: Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body.Conclusions: Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audiovisual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans.