Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
Marta Valle, Montserrat Puntes, Jimena Coimbra, Maite Garrido, Judit Claramunt, Izabela Lomnicka, Marian Waguespack, Jordi Riba, Ana Maqueda, Peter H. Addy, Rosa María Antonijoan, María Rosa Ballester, M. J. González, Steven A. Barker, Matthew W. Johnson, Roland R. Griffiths
The International Journal of Neuropsychopharmacology February 12, 2016 DOI: 10.1093/ijnp/pyw016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy volunteers with experience with psychedelic drugs |
| Interventions | Salvinorin-A Naltrexone Ketanserin |
| Dose | 1 mg of vaporized salvinorin-A; 50 mg of naltrexone orally; 40 mg of ketanserin orally |
| Topics | Serotonin Salvia divinorum |
| Keywords | Ketanserin Naltrexone Hallucinogen Pharmacology Placebo Opioid Receptor antagonist Ritanserin Anesthesia |
| Citations | 31 |
| Key findings | Salvinorin-A's subjective and physiological effects are mediated by kappa-opioid receptor agonism, not serotonin-2A receptor agonism. |
Abstract
Background: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short-lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa-opioid receptor rather than at the serotonin-2A receptor. Here, we assessed the involvement of kappa-opioid receptor and serotonin-2A agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans.
Methods: We conducted a placebo-controlled, randomized, double-blind study with 2 groups of 12 healthy volunteers with experience with psychedelic drugs. There were 4 experimental sessions. In group 1, participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo, and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50mg orally. In group 2, participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo, and ketanserin+salvinorin-A. Ketanserin, a selective serotonin-2A antagonist, was administered at a dose of 40mg orally.
Results: Inhalation of 1mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin.
Conclusions: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism.
Comparable studies
Other randomized controlled trials on salvia divinorum, most cited first.
Citations in the library
Cited by 14
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- The Altered States Database: Psychometric data from a systematic literature review. Scientific Data November 23, 2022
- Can psilocybin be safely administered under medical supervision? A systematic review of adverse event reporting in clinical trials Drug Science, Policy and Law 2022
and 9 more in the library
Cites 23
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Psychopharmacology March 1, 2004
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
and 18 more in the library