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Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception
Ana Elda Maqueda1, Marta Valle1, Peter H Addy1
1Human Neuropsychopharmacology Group. Sant Pau Institute of Biomedical Research (IIB-Sant Pau). Sant Antoni María Claret, Barcelona, Spain (Drs Maqueda and Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Drs Valle, Antonijoan, Puntes, Coimbra, Ballester, Garrido, González, Claramunt, and Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau. Sant Antoni María Claret, 167, 08025 Barcelona, Spain (Dr Valle); Medical Informatics, VA Connecticut Healthcare System, West Haven, CT (Dr Addy); Medical Informatics, Yale University School of Medicine, New Haven, CT (Dr Addy); Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA (Dr Barker); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths).
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 psychedelic-like 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 audio-visual 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.