dc.contributor.author |
Maqueda, Ana Elda |
dc.contributor.author |
Valle, Marta |
dc.contributor.author |
Addy, Peter H. |
dc.contributor.author |
Antonijoan Arbós, Rosa Ma. |
dc.contributor.author |
Puntes, Montserrat |
dc.contributor.author |
Coimbra, Jimena |
dc.contributor.author |
Ballester, Maria Rosa |
dc.contributor.author |
Garrido, Maite |
dc.contributor.author |
González, Mireia |
dc.contributor.author |
Claramunt, Judit |
dc.contributor.author |
Barker, Steven |
dc.contributor.author |
Lomnicka, Izabela |
dc.contributor.author |
Waguespack, Marian |
dc.contributor.author |
Johnson, Matthew W. |
dc.contributor.author |
Griffiths, Roland R. |
dc.contributor.author |
Riba, Jordi |
dc.date |
2016 |
dc.identifier |
https://ddd.uab.cat/record/254104 |
dc.identifier |
urn:10.1093/ijnp/pyw016 |
dc.identifier |
urn:oai:ddd.uab.cat:254104 |
dc.identifier |
urn:pmcid:PMC4966277 |
dc.identifier |
urn:pmc-uid:4966277 |
dc.identifier |
urn:pmid:26874330 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:4966277 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Instituto de Salud Carlos III PI12/02758 |
dc.relation |
Instituto de Salud Carlos III CP04/00121 |
dc.relation |
International journal of neuropsychopharmacology ; Vol. 19 (february 2016) |
dc.rights |
open access |
dc.rights |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. |
dc.rights |
https://creativecommons.org/licenses/by-nc/4.0/ |
dc.subject |
Salvinorin-A |
dc.subject |
Naltrexone |
dc.subject |
Ketanserin |
dc.subject |
Kappa opioid receptor antagonism |
dc.subject |
Serotonin-2a antagonism |
dc.subject |
Human pharmacology |
dc.title |
Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans |
dc.type |
Article |
dc.description.abstract |
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. 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. 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. 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. |