, Volume 226, Issue 2, pp 381–392 | Cite as

Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects

  • Katherine A. MacLean
  • Matthew W. Johnson
  • Chad J. Reissig
  • Thomas E. Prisinzano
  • Roland R. Griffiths
Original Investigation



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.


This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use.


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.


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.


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.


Salvinorin A Salvia divinorum Kappa opioid agonist Hallucinogen Psychedelic Dissociative Human 



This work was supported by the National Institute on Drug Abuse (NIDA) through R01DA003889, T32DA007209, and R01DA018151. The authors would like to thank Annie Umbricht, M.D. and the medical staff at the Behavioral Pharmacology Research Unit for medical screening and medical coverage; Linda Felch for statistical analysis; Janna Bonesteel, Crystal Barnhouser, Eric Richter, Jenna Cohen, Samantha Gebhart, and Margaret Klinedinst for assistance in conducting sessions and collecting and organizing the data; Mary Cosimano, MSW, for conducting psychological screenings; and Ronald W. Wood, PhD for helpful discussions on drug volatilization.

Conflict of interest

All authors declare that they have no conflicts of interest.

Supplementary material

213_2012_2912_MOESM1_ESM.pdf (83 kb)
ESM 1 (PDF 83 kb)
213_2012_2912_MOESM2_ESM.pdf (55 kb)
ESM 2 (PDF 54 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Katherine A. MacLean
    • 1
  • Matthew W. Johnson
    • 1
  • Chad J. Reissig
    • 1
  • Thomas E. Prisinzano
    • 2
  • Roland R. Griffiths
    • 1
    • 3
  1. 1.Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral SciencesJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of Medicinal ChemistryThe University of KansasLawrenceUSA
  3. 3.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA

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