Salvinorin-A: A Perception-Modifying Drug with a Unique Neurophysiological Profile
Jordi Riba, Ph.D.
Salvinorin-A (SA) is a potent perception-modifying drug found in the leaves of the plant Salvia divinorum. Unlike serotonin-2A receptor agonists such as DMT, LSD and psilocybin, SA is a selective kappa-opioid receptor agonist. Here I present the findings of the research program on the human pharmacology of salvinorin-A conducted by our group, the Human Neuropsychopharmacology Research Group at the Hospital de Sant Pau, in Barcelona, Spain. Initial data obtained from experienced psychedelic users show that the pattern of subjective effects has clear differences with that of the classical psychedelics. While participants also experience intense visual and auditory phenomena, SA dose-dependently blocks external audio-visual information, with a total loss of contact with the body and external reality at high doses. Using pre-treatment with selective receptor antagonists we have demonstrated for the first time in humans that blockade of opioid receptors effectively counteracts SA-induced subjective, cardiovascular and neuroendocrine effects. On the contrary, blockade of the serotonin-2A receptor, the target of classical psychedelics, does not modify the response to SA. Our latest study assessing the effects of SA in spontaneous brain oscillations has evidenced that the drug induces a unique pattern of neurophysiological effects. While it shares with ayahuasca, LSD and psilocybin an alpha-rhythm-suppressing action, its main neurophysiological signature is an atypical enhancement of slow delta activity. Delta increases are observed over most of the brain, with the maxima located over auditory and visual cortex in the temporal lobes. We postulate that the intense delta-enhancing effect induced by SA is responsible for the marked dissociative effects that differentiate this drug from serotonin-2A psychedelics.
Jordi Riba holds a Ph.D. in Pharmacology. He leads the Human Neuropsychopharmacology Research Group at Sant Pau Hospital in Barcelona. He has a broad interest in psychoactive drugs with publications on psychedelics, psychostimulants, cannabinoids, and kappa receptor agonists. He has been studying ayahuasca for over fifteen years and has published nearly forty journal articles and book chapters on the subject. He has also supervised two doctorate theses on the acute and long-term effects of ayahuasca in humans, and collaborated in the first clinical studies involving ayahuasca administration to patients with depression. His current research deals with the post-acute psychedelic “after-glow” and the use of ayahuasca in the treatment of various psychiatric conditions. He is also investigating the neuroprotective and neurogenic potential of ayahuasca alkaloids. Initial data obtained from studies in animals have revealed that several active principles present in the tea protect brain cells from hypoxia and stimulate the birth of new neurons in adult mice. These stunning results open a whole new avenue of research for ayahuasca. Potential applications of its active principles range from depression, to neurodegenerative disorders, to neural deficits associated with hypoxia and trauma.