Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects
This double-blind, placebo-controlled study (n=8) assessed the subjective effects of salvinorin A (0.026-1.470mg/70kg) and found that they only partially overlap with classic hallucinogens.
Authors
- Roland Griffiths
- Matthew Johnson
- Katherine MacLean
Published
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.
Research Summary of 'Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects'
Introduction
Salvinorin A is the principal psychoactive constituent of Salvia divinorum and is pharmacologically distinct from classic serotonergic hallucinogens: it is a non‑nitrogenous, selective kappa opioid receptor agonist with negligible activity at 5‑HT2A. Nonhuman studies have characterised its pharmacology and behavioural effects, and survey-based human reports describe intense, often idiosyncratic subjective effects, but controlled human laboratory data remain limited and sometimes inconsistent. Prior controlled work from this group and others suggested dose‑related subjective effects after inhalation, but questions remain about the phenomenology, dissociative and cognitive consequences, and the persistence of effects. Maclean and colleagues designed a double‑blind, placebo‑controlled human laboratory study to extend preliminary observations and to characterise dose‑related effects of inhaled salvinorin A across a range of outcomes. Their aims were to document time course and dose–response relationships for subjective, observer and physiological measures, to test effects on recall and recognition memory, to capture qualitative aspects of experience via open‑ended narratives, and to assess persisting effects approximately 1 month after exposure.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Authors
- APA Citation
MacLean, K. A., Johnson, M. W., Reissig, C. J., Prisinzano, T. E., & Griffiths, R. R. (2013). Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology, 226(2), 381-392. https://doi.org/10.1007/s00213-012-2912-9
References (8)
Papers cited by this study that are also in Blossom
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Johnson, M. W., Maclean, K. A., Reissig, C. J. et al. · Drug and Alcohol Dependence (2011)
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