title: Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects.
abstract: BACKGROUND
  Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A.
  
  
  OBJECTIVE
  This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use.
  
  
  METHODS
  Eight healthy hallucinogen-using adults inhaled up to 16 doses of salvinorin A (0.375-21 μg/kg) in ascending order. Physiological, behavioral, and subjective effects were assessed every 2 min for 60 min after administration. Qualitative subjective effects were assessed retrospectively via questionnaires at the end of sessions. Persisting effects were assessed 1 month later.
  
  
  RESULTS
  Orderly dose-related effects peaked at 2 min and then rapidly dissipated, replicating previous findings. Subjective effects were intense, with maximal drug strength ratings or unresponsiveness frequently observed at high doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale, Pharmacological Class Questionnaire) suggested some overlap with serotonergically mediated classic hallucinogens. Salvinorin A also produced dose-related dissociative effects and impairments in recall/recognition memory. At 1-month follow-up, there was no evidence of persisting adverse effects. Participants reported that salvinorin A effects were qualitatively different from other drugs.
  
  
  CONCLUSIONS
  Salvinorin A produces a unique profile of subjective and cognitive effects, including strong dissociative effects and memory impairment, which only partially overlap with classic hallucinogen effects. Along with nonhuman studies of salvinorin A, these results are important for understanding the neurobiology of the kappa opioid system and may ultimately have important therapeutic applications.
authors.affiliation: Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224-6823, USA. katherine.a.maclean@gmail.com
authors.forename: Katherine A
authors.initials: KA
authors.lastname: MacLean
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Reissig
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
authors.forename: Roland R
authors.initials: RR
authors.lastname: Griffiths
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D004213:Dissociative Disorders / Q000139:chemically induced*; D045785:Diterpenes, Clerodane / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists
chemical_list: D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D017473:Receptors, Opioid, kappa; C090499:salvinorin A