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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

Psychopharmacology March 1, 2013 DOI: 10.1007/s00213-012-2912-9 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled study Qualitative Peer reviewed
Sample size 8
Population Healthy hallucinogen-using adults
Intervention Salvinorin A
Dose 0.375-21 μg/kg
Duration 60 min after administration, with 1-month follow-up
Topics Altered states of consciousness Salvia divinorum
Keywords Natural compound Plant extract Dissociative states Dissociation Psychoactive effects Psychotomimetic Mind-altering Kappa opioid system Kor Opioid receptor Neuropharmacology Mechanism of action Therapeutic potential Medical applications Drug development Future therapies Clinical potential
Citations 134
Key points Inhaled salvinorin A produces intense, dose-related dissociative effects and memory impairment that peak at 2 minutes and rapidly dissipate, with a unique subjective profile partially overlapping classic hallucinogens.

Abstract

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.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • State of the evidence: Salvia divinorum Mixed

    Inhaled salvinorin A produced intense dose-related dissociative effects and memory impairment peaking at 2 minutes and dissipating rapidly, with no persisting adverse effects at 1-month follow-up.

    Synthesized

Comparable studies

Other randomized controlled trials on salvia divinorum, most cited first.

Study Year Design Participants
Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Psychologically and physically healthy hallucinogen-using adults 2011 Double-blind, placebo controlled study n = 4
Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the κ opioid agonist Salvinorin A in humans. Healthy individuals who had previously used Salvia 2012 Randomized controlled trial n = 10
Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans Healthy volunteers with previous experience in the use of psychedelics 2015 Placebo-controlled dose-escalation study n = 8
Acute and post-acute behavioral and psychological effects of salvinorin A in humans. Middle-aged, well-educated, hallucinogen-experienced adults 2012 Randomized controlled trial n = 30
The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain Human adults 2020 Placebo-controlled, within-subject study

Citations in the library

Cited by 60

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Cites 40

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