title: Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial.
abstract: BACKGROUND
  Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.
  
  
  OBJECTIVE
  The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.
  
  
  METHODS
  Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design.
  
  
  RESULTS
  No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported "typical" effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL).
  
  
  CONCLUSIONS
  Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.
authors.affiliation: Addiction and Pharmacology Research Laboratory, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Mendelson
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Coyle
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lopez
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Baggott
authors.forename: Keith
authors.initials: K
authors.lastname: Flower
authors.forename: E Thomas
authors.initials: ET
authors.lastname: Everhart
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Munro
authors.forename: Gantt P
authors.initials: GP
authors.lastname: Galloway
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D001682:Biological Availability; D045785:Diterpenes, Clerodane / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D027544:Salvia / Q000737:chemistry*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D017473:Receptors, Opioid, kappa; C090499:salvinorin A