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.
authors.affiliation: Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA mwj@jhu.edu.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Johnson
authors.affiliation: Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: MacLean
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caspers
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
authors.affiliation: Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Roland R
authors.initials: RR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D045785:Diterpenes, Clerodane / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D001239:Inhalation; D008297:Male; D017473:Receptors, Opioid, kappa / Q000819:agonists; D027544:Salvia / Q000737:chemistry; D055815:Young Adult
chemical_list: D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D006728:Hormones; D017473:Receptors, Opioid, kappa; C090499:salvinorin A
keywords: Salvia divinorum; cortisol; endocrine; pharmacokinetics; prolactin; salvinorin A