Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
Por:
Maqueda, AE, Valle, M, Addy, PH, Antonijoan, RM, Puntes, M, Coimbra, J, Ballester, MR, Garrido, M, Gonzalez, M, Claramunt, J, Barker, S, Lomnicka, I, Waguespack, M, Johnson, MW, Griffiths, RR, Riba, J
Publicada:
1 jul 2016
Resumen:
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.
Filiaciones:
Maqueda, AE:
St Pau Inst Biomed Res IIB St Pau, Human Neuropsychopharmacol Grp, Barcelona, Spain
Valle, M:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Univ Autonoma Barcelona, Dept Farmacol & Terapeut, Barcelona, Spain
CIBERSAM, Ctr Invest Biomed Red Salud Mental, Barcelona, Spain
IIB St Pau, Pharmacokinet & Pharmacodynam Modelling & Simulat, Barcelona, Spain
Addy, PH:
VA Connecticut Healthcare Syst, Med Informat, West Haven, CT USA
Yale Univ, Sch Med, Med Informat, New Haven, CT USA
Antonijoan, RM:
Univ Autonoma Barcelona, Dept Farmacol & Terapeut, Barcelona, Spain
CIBERSAM, Ctr Invest Biomed Red Salud Mental, Barcelona, Spain
Puntes, M:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Coimbra, J:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Ballester, MR:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Garrido, M:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Gonzalez, M:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Claramunt, J:
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Barker, S:
Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Skip Bertman Dr,River Rd, Baton Rouge, LA 70803 USA
Lomnicka, I:
Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Skip Bertman Dr,River Rd, Baton Rouge, LA 70803 USA
Waguespack, M:
Louisiana State Univ, Sch Vet Med, Dept Comparat Biomed Sci, Skip Bertman Dr,River Rd, Baton Rouge, LA 70803 USA
Johnson, MW:
Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA
Griffiths, RR:
Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA
Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
Riba, J:
St Pau Inst Biomed Res IIB St Pau, Human Neuropsychopharmacol Grp, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Ctr Invest Medicaments, Barcelona, Spain
Univ Autonoma Barcelona, Dept Farmacol & Terapeut, Barcelona, Spain
CIBERSAM, Ctr Invest Biomed Red Salud Mental, Barcelona, Spain
Gold, Green Published
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