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

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 su...

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Autores: Maqueda, Ana Elda, Valle, Marta|||0000-0002-3515-251X, Addy, Peter H., Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125, Puntes, Montserrat, Coimbra, Jimena, Ballester, Maria Rosa|||0000-0002-0472-9558, Garrido, Maite, González, Mireia, Claramunt, Judit, Barker, Steven|||0000-0002-5755-3496, Lomnicka, Izabela, Waguespack, Marian, Johnson, Matthew W., Griffiths, Roland R., Riba, Jordi|||0000-0002-9375-8421
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:254104
Acceso en línea:https://ddd.uab.cat/record/254104
https://dx.doi.org/urn:doi:10.1093/ijnp/pyw016
Access Level:acceso abierto
Palabra clave:Salvinorin-A
Naltrexone
Ketanserin
Kappa opioid receptor antagonism
Serotonin-2a antagonism
Human pharmacology
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spelling Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in HumansMaqueda, Ana EldaValle, Marta|||0000-0002-3515-251XAddy, Peter H.Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125Puntes, MontserratCoimbra, JimenaBallester, Maria Rosa|||0000-0002-0472-9558Garrido, MaiteGonzález, MireiaClaramunt, JuditBarker, Steven|||0000-0002-5755-3496Lomnicka, IzabelaWaguespack, MarianJohnson, Matthew W.Griffiths, Roland R.Riba, Jordi|||0000-0002-9375-8421Salvinorin-ANaltrexoneKetanserinKappa opioid receptor antagonismSerotonin-2a antagonismHuman pharmacologySalvinorin-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. 22016-01-0120162016-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/254104https://dx.doi.org/urn:doi:10.1093/ijnp/pyw016reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02758Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100004587 CP04/00121open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2541042026-06-06T12:50:31Z
dc.title.none.fl_str_mv Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
title Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
spellingShingle Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
Maqueda, Ana Elda
Salvinorin-A
Naltrexone
Ketanserin
Kappa opioid receptor antagonism
Serotonin-2a antagonism
Human pharmacology
title_short Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
title_full Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
title_fullStr Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
title_full_unstemmed Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
title_sort Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans
dc.creator.none.fl_str_mv Maqueda, Ana Elda
Valle, Marta|||0000-0002-3515-251X
Addy, Peter H.
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Puntes, Montserrat
Coimbra, Jimena
Ballester, Maria Rosa|||0000-0002-0472-9558
Garrido, Maite
González, Mireia
Claramunt, Judit
Barker, Steven|||0000-0002-5755-3496
Lomnicka, Izabela
Waguespack, Marian
Johnson, Matthew W.
Griffiths, Roland R.
Riba, Jordi|||0000-0002-9375-8421
author Maqueda, Ana Elda
author_facet Maqueda, Ana Elda
Valle, Marta|||0000-0002-3515-251X
Addy, Peter H.
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Puntes, Montserrat
Coimbra, Jimena
Ballester, Maria Rosa|||0000-0002-0472-9558
Garrido, Maite
González, Mireia
Claramunt, Judit
Barker, Steven|||0000-0002-5755-3496
Lomnicka, Izabela
Waguespack, Marian
Johnson, Matthew W.
Griffiths, Roland R.
Riba, Jordi|||0000-0002-9375-8421
author_role author
author2 Valle, Marta|||0000-0002-3515-251X
Addy, Peter H.
Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125
Puntes, Montserrat
Coimbra, Jimena
Ballester, Maria Rosa|||0000-0002-0472-9558
Garrido, Maite
González, Mireia
Claramunt, Judit
Barker, Steven|||0000-0002-5755-3496
Lomnicka, Izabela
Waguespack, Marian
Johnson, Matthew W.
Griffiths, Roland R.
Riba, Jordi|||0000-0002-9375-8421
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Salvinorin-A
Naltrexone
Ketanserin
Kappa opioid receptor antagonism
Serotonin-2a antagonism
Human pharmacology
topic Salvinorin-A
Naltrexone
Ketanserin
Kappa opioid receptor antagonism
Serotonin-2a antagonism
Human pharmacology
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2
2016-01-01
2016
2016-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/254104
https://dx.doi.org/urn:doi:10.1093/ijnp/pyw016
url https://ddd.uab.cat/record/254104
https://dx.doi.org/urn:doi:10.1093/ijnp/pyw016
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02758
Ministerio de Sanidad y Consumo https://doi.org/10.13039/501100004587 CP04/00121
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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