Depressive DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Chronic PainImmunology & InflammationMedicinal Chemistry & Drug DevelopmentSalvia Divinorum

A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics

This review (2016) examines the psychoactive properties and therapeutic potential of Salvinorin A, a kappa-opioid receptor agonist that is the bioactive constituent of the indigenous plant Salvia divinorum. Next to highly potent psychoactive properties as a dissociative hallucinogen, preliminary scientific evidence also indicates it may have broad-range therapeutic applications for treating addiction, inflammation, pain, and depression.

Authors

  • Cruz, A. P. M.
  • Domingos, S.
  • Gallardo, E.

Published

Phytochemistry
meta Study

Abstract

Review: Until the mid-60s, only the Mazatecs, an indigenous group from Oaxaca, Mexico, used Salvia Divinorum (S. divinorum) due to its hallucinogen properties. Later it was found that the hallucinogen effects of this plant were caused by the presence of a neoclerodane diterpene Salvinorin A (salvinorin A), which is a highly selective agonist of kappa-opioid receptor (KOR) that cause more intense hallucinations than the common hallucinogens as lysergic acid, mushrooms, ecstasy and others. In fact, smoking of only 200-500 μg of S. divinorum leaves is enough to produce these effects thus making it the most potent natural occurring hallucinogen known. Due to its legal status in various countries, this compound has gained a worldwide popularity as a drug of abuse with an easy access through smartshops and internet. Furthermore, salvinorin A gathered an increased interest in the scientific community thanks to its unique structure and properties, and various studies demonstrated that salvinorin A has antinociceptive, antidepressant, in some circumstances pro-depressant and anti-addictive effects that have yielded potential new avenues for research underlying salvinorin A and its semi-synthetic analogs as therapeutic agents.

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Research Summary of 'A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics'

Introduction

Salvia divinorum is a perennial shrub traditionally used by the Mazatec people of Oaxaca for ritual and medicinal purposes. Cruz and colleagues explain that the principal bioactive constituent of the plant is salvinorin A, a non‑nitrogenous neoclerodane diterpene that produces intense, short‑lived hallucinations and is a highly selective kappa‑opioid receptor (KOR) agonist. Clerodane diterpenes in general have attracted interest because of diverse biological activities, and salvinorin A stands out because its structure and receptor interactions differ from classical alkaloid opioids and serotonergic psychedelics. This paper reviews the pharmacology, pharmacokinetics, behavioural effects and potential therapeutic roles of salvinorin A, and highlights unresolved questions about its mechanism, metabolism, toxicity and long‑term effects. The authors aim to synthesise preclinical and observational evidence on antinociceptive, antidepressant, anti‑addiction, neuroprotective, anti‑inflammatory and gastrointestinal activities, and to discuss potential applications and safety concerns for human therapeutics.

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Study Details

References (1)

Papers cited by this study that are also in Blossom

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum

Johnson, M. W., Maclean, K. A., Reissig, C. J. et al. · Drug and Alcohol Dependence (2011)

132 cited

Cited By (1)

Papers in Blossom that reference this study

Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A

Bagdasarian, F. A., Hansen, H. D., Chen, J. et al. · ACS Chemical Neuroscience (2024)

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