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

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Abstract

Rationale

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. 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, Matthew W. Johnson, Chad J. Reissig & Roland R. Griffiths

  2. Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS, 66045-7582, USA

    Thomas E. Prisinzano

  3. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21224-6823, USA

    Roland R. Griffiths

Authors
  1. Katherine A. MacLean
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  2. Matthew W. Johnson
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  3. Chad J. Reissig
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  4. Thomas E. Prisinzano
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  5. Roland R. Griffiths
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Correspondence to Katherine A. MacLean.

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MacLean, K.A., Johnson, M.W., Reissig, C.J. et al. Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology 226, 381–392 (2013). https://doi.org/10.1007/s00213-012-2912-9

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  • DOI: https://doi.org/10.1007/s00213-012-2912-9

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