title: Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the κ opioid agonist Salvinorin A in humans.
abstract: BACKGROUND
  Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the κ opiate receptor-is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans.
  
  
  METHODS
  In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia.
  
  
  RESULTS
  SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects.
  
  
  CONCLUSIONS
  SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects.
authors: Psychiatry Service, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA. mohini.ranganathan@yale.edu
authors: Mohini
authors: M
authors: Ranganathan
authors: Ashley
authors: A
authors: Schnakenberg
authors: Patrick D
authors: PD
authors: Skosnik
authors: Bruce M
authors: BM
authors: Cohen
authors: Brian
authors: B
authors: Pittman
authors: R Andrew
authors: RA
authors: Sewell
authors: Deepak Cyril
authors: DC
authors: D'Souza
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D002319:Cardiovascular System / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D045785:Diterpenes, Clerodane / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D013287:Illicit Drugs; D008297:Male; D010465:Perception / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D011605:Psychoses, Substance-Induced / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012677:Sensation / Q000187:drug effects
chemical_list: D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D013287:Illicit Drugs; D017473:Receptors, Opioid, kappa; D011388:Prolactin; C090499:salvinorin A; D006854:Hydrocortisone