Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans

Jacob M. Hooker, Youwen Xu, Wynne K Schiffer, Colleen Shea, Pauline Carter, Joanna S. Fowler

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Salvia divinorum, a mint plant originally used by the Mazatecs of Oaxaca, Mexico in spiritual rituals has gained popularity, in smoked form, as a legal hallucinogen in the United States and Europe. Abuse results in rapid onset and short-lasting effects that include visual hallucinations and motor-function impairment. Salvinorin A, the psychoactive component of S. divinorum, is a uniquely potent agonist at κ-opioid receptors, targets for new therapeutic drugs. We labeled salvinorin A with C-11 by acylation of salvinorin B with [11C]-acetyl chloride to study whether its kinetic behavior in the brain parallels its uniquely fast, yet brief physiological effects. Positron emission tomography (PET) studies performed in 6 adult female baboons indicated extremely rapid brain uptake reaching a peak accounting for 3.3% of the total administered dose in 40 s and clearing with a half-life of 8 min. [11C]-salvinorin A was distributed throughout the brain with the highest concentration in the cerebellum and a notable concentration in the visual cortex, perhaps accounting for its physiological effects when smoked. Naloxone administration did not reduce the overall concentration of [11C]-salvinorin A significantly nor did it change its regional distribution. Peripheral organ kinetics suggested at least two modes of metabolism and excretion occur: through the renal and biliary systems. Our findings have revealed that the exceptionally rapid uptake and brief duration of salvinorin A in the brain match the time-course of visual hallucinations for S. divinorum when smoked. The effects of salvinorin A may occur at < 10 μg in the human brain, emphasizing its remarkable potency.

Original languageEnglish (US)
Pages (from-to)1044-1050
Number of pages7
JournalNeuroImage
Volume41
Issue number3
DOIs
StatePublished - Jul 1 2008

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