Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans.

Autor:	Maqueda AE; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Valle M; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Addy PH; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Antonijoan RM; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Puntes M; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Coimbra J; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Ballester MR; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Garrido M; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., González M; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Claramunt J; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Barker S; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Lomnicka I; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Waguespack M; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Johnson MW; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Griffiths RR; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths)., Riba J; Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, Barcelona, Spain (Ms Maqueda and Dr Riba); Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (Dr Valle, Dr Puntes, Dr Coimbra, Ms Ballester, Ms Garrido, Ms González, Ms Claramunt, and Dr Riba); Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain (Drs Valle, Antonijoan, and Riba); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain (Drs Valle, Antonijoan, and Riba); Pharmacokinetic and Pharmacodynamic Modelling and Simulation, IIB Sant Pau, Sant Antoni María Claret, 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 (Drs Barker, Lomnicka, and Waguespack); Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (Drs Johnson and Griffiths); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (Dr Griffiths). jriba@santpau.cat.
Jazyk:	angličtina
Zdroj:	The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2016 Jul 05; Vol. 19 (7). Date of Electronic Publication: 2016 Jul 05 (Print Publication: 2016).
DOI:	10.1093/ijnp/pyw016
Abstrakt:	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. (© The Author 2016. Published by Oxford University Press on behalf of CINP.)
Databáze:	MEDLINE
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