Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans

Matthew W. Johnson; Katherine A. MacLean; Michael J. Caspers; Thomas E. Prisinzano; Roland R. Griffiths

doi:10.1177/0269881116629125

Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans

Matthew W. Johnson, Katherine A. MacLean, Michael J. Caspers, Thomas E. Prisinzano, Roland R. Griffiths

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

Original language	English
Pages (from-to)	323-329
Number of pages	7
Journal	Journal of Psychopharmacology
Volume	30
Issue number	4
DOIs	https://doi.org/10.1177/0269881116629125
State	Published - Apr 1 2016

Bibliographical note

Funding Information:
The authors would like to thank Annie Umbricht and the medical staff at the Behavioral Pharmacology Research Unit for medical screening and medical coverage; Mary Cosimano for conducting psychological screenings; Chad J Reissig, Janna Bonesteel, Crystal Barnhouser, Eric Richter, Jenna Cohen, Samantha Gebhart, and Margaret Klinedinst for assistance in conducting sessions and collecting and organizing the data; Ethan Hurwitz for assistance with manuscript preparation; Linda Felch for statistical analysis; and Michelle Rudek-Renaut for analyses of prolactin and cortisol. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute on Drug Abuse (NIDA) through R01DA003889, T32DA007209, and R01DA018151. Analysis of prolactin and cortisol was supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins with grants P30 CA006973 from the National Institutes of Health (NIH) and UL1 RR025005 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The project described was also supported in part by Grant Number UL1 RR025005.

Publisher Copyright:
© The Author(s).2016

Keywords

Salvia divinorum
cortisol
endocrine
pharmacokinetics
prolactin
salvinorin A

ASJC Scopus subject areas

Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1177/0269881116629125

Cite this

@article{ef7c006eec85499ea6bb438afd38bcfb,

title = "Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans",

abstract = "Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.",

keywords = "Salvia divinorum, cortisol, endocrine, pharmacokinetics, prolactin, salvinorin A",

author = "Johnson, {Matthew W.} and MacLean, {Katherine A.} and Caspers, {Michael J.} and Prisinzano, {Thomas E.} and Griffiths, {Roland R.}",

note = "Funding Information: The authors would like to thank Annie Umbricht and the medical staff at the Behavioral Pharmacology Research Unit for medical screening and medical coverage; Mary Cosimano for conducting psychological screenings; Chad J Reissig, Janna Bonesteel, Crystal Barnhouser, Eric Richter, Jenna Cohen, Samantha Gebhart, and Margaret Klinedinst for assistance in conducting sessions and collecting and organizing the data; Ethan Hurwitz for assistance with manuscript preparation; Linda Felch for statistical analysis; and Michelle Rudek-Renaut for analyses of prolactin and cortisol. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute on Drug Abuse (NIDA) through R01DA003889, T32DA007209, and R01DA018151. Analysis of prolactin and cortisol was supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins with grants P30 CA006973 from the National Institutes of Health (NIH) and UL1 RR025005 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The project described was also supported in part by Grant Number UL1 RR025005. Publisher Copyright: {\textcopyright} The Author(s).2016",

year = "2016",

month = apr,

day = "1",

doi = "10.1177/0269881116629125",

language = "English",

volume = "30",

pages = "323--329",

number = "4",

}

TY - JOUR

T1 - Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans

AU - Johnson, Matthew W.

AU - MacLean, Katherine A.

AU - Caspers, Michael J.

AU - Prisinzano, Thomas E.

AU - Griffiths, Roland R.

N1 - Funding Information: The authors would like to thank Annie Umbricht and the medical staff at the Behavioral Pharmacology Research Unit for medical screening and medical coverage; Mary Cosimano for conducting psychological screenings; Chad J Reissig, Janna Bonesteel, Crystal Barnhouser, Eric Richter, Jenna Cohen, Samantha Gebhart, and Margaret Klinedinst for assistance in conducting sessions and collecting and organizing the data; Ethan Hurwitz for assistance with manuscript preparation; Linda Felch for statistical analysis; and Michelle Rudek-Renaut for analyses of prolactin and cortisol. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute on Drug Abuse (NIDA) through R01DA003889, T32DA007209, and R01DA018151. Analysis of prolactin and cortisol was supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins with grants P30 CA006973 from the National Institutes of Health (NIH) and UL1 RR025005 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The project described was also supported in part by Grant Number UL1 RR025005. Publisher Copyright: © The Author(s).2016

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

AB - Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

KW - Salvia divinorum

KW - cortisol

KW - endocrine

KW - pharmacokinetics

KW - prolactin

KW - salvinorin A

UR - http://www.scopus.com/inward/record.url?scp=84961239345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961239345&partnerID=8YFLogxK

U2 - 10.1177/0269881116629125

DO - 10.1177/0269881116629125

M3 - Article

C2 - 26880225

AN - SCOPUS:84961239345

VL - 30

SP - 323

EP - 329

IS - 4

ER -

Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this