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
Neuroimage July 1, 2008 DOI: 10.1016/j.neuroimage.2008.03.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Adult female baboons |
| Interventions | [11C]-salvinorin A naloxone |
| Topics | Salvia divinorum |
| Keywords | Compound Labeled version Tiny amounts Profound impact Pharmacokinetics: rapid action Swift brain uptake Clearance Kinetic profile Quick onset Brief effects Peak brain concentration Clears Under a minute Within eight Baboons Intense effects Potent hallucinogen |
| Citations | 106 |
| Key findings | Salvinorin A shows exceptionally rapid brain uptake and clearance that match the brief time-course of visual hallucinations when smoked, with effects possibly occurring at less than 10 micrograms in the human brain. |
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 kappa-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 mug in the human brain, emphasizing its remarkable potency.
Comparable studies
Other observational and cohort studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Salvia divinorum: effects and use among YouTube users. YouTube video posters using salvia | 2010 | Observational study using video analysis | n = 34 |
| In vitro stability and metabolism of salvinorin A in rat plasma. Rat plasma | 2009 | Observational study | |
| Salvia divinorum: exposures reported to a statewide poison control system over 10 years. Exposures to Salvia divinorum reported to the California Poison Control System | 2011 | Retrospective review | n = 37 |
| Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. Healthy adults | 2016 | Observational study | n = 6 |
| A Content Analysis of Salvia Divinorum Use on YouTube Users who posted videos of themselves using Salvia divinorum on YouTube | 2013 | Observational study |
Citations in the library
Cited by 53
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Use patterns and self-reported effects of Salvia divinorum: an internet-based survey. Drug and Alcohol Dependence October 1, 2010
- Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders Frontiers in Pharmacology September 8, 2015
- Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V June 1, 2009
- Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid. Journal of Pharmacology and Experimental Therapeutics February 1, 2009
and 48 more in the library
Cites 11
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Opioid receptors and legal highs:Salvia divinorumand Kratom Clinical Toxicology 2008
- Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence November 8, 2006
- Salvinorin A: from natural product to human therapeutics. Molecular interventions October 1, 2006
- Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates. Synapse December 1, 2005
and 6 more in the library