Salvia divinorum is a member of the mint family with known hallucinogenic properties which have been known for centuries. Historically it has been used in shaman rituals in the Oaxaca Mexico region. The psychoactive substance within salvia divinorum has been isolated and is called salvinorin A (salv A). Unlike the typical hallucinogenic drugs that act on the serotonergic system, salv A primarily acts on the kappa opioid system. The Drug Enforcement Agency (DEA) has taken a recent interest in this compound and is currently investigating whether it should be scheduled as a controlled substance. Currently thirteen states heave enacted laws regarding the use of salv A. The question on the scheduling of salv A and the synthetic isomers of the drug may produce an interesting debate.

The literature on the addictive properties is still rather sparse and replication of the existing studies would be beneficial. A preclinical study in rodents demonstrated that salv A produced a decrease in dopamine and dopamine transmission, the endogenous neurotransmitter associated with addiction, and no effect on locomotor activity (a common test for the stimulant effects of a drug). These depressive effects would seem to be contrary to the notion of salv A being an addictive drug. Furthermore, these effects may lend value to salv A and its analogs as potential pharmacotherapeutics for neuropsychiatric conditions including addiction and mood disorders.

Other studies have demonstrated the opposite effect, where low doses of salv A increase dopamine efflux, produce a conditioned place preference, and rats examined during intracerebroventricular self-administration will self-infuse the drug. The latter two tests are common preclinical assessments of the rewarding properties associated with a drug. There exists a discrepancy in the literature on whether salv A will substitute for LSD in rodent studies using drug discrimination. On such study in rodents demonstrated that salv A and LSD share similar stimulus properties which is contrary to previous reports.

Recently a controlled behavioral pharmacology investigation was conducted in humans to assess the physiological and subjective effects of salv A. It showed that salv A does not induce changes in blood pressure or heart rate although its subjective effects are similar to other hallucinogenic drugs. Given that salv A produces hallucinogenic effects similar to other known scheduled hallucinogens careful consideration needs to be given to legality of this substance.

References

Braida D, Limonta V, Capurro V, Fadda P, Rubino T, Mascia P, Zani A, Gori E, Fratta W, Parolaro D, & Sala M (2008). Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Biological psychiatry, 63 (3), 286-92 PMID: 17920565

Carlezon WA Jr, Béguin C, DiNieri JA, Baumann MH, Richards MR, Todtenkopf MS, Rothman RB, Ma Z, Lee DY, & Cohen BM (2006). Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. The Journal of pharmacology and experimental therapeutics, 316 (1), 440-7 PMID: 16223871

Gehrke BJ, Chefer VI, & Shippenberg TS (2008). Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum. Psychopharmacology, 197 (3), 509-17 PMID: 18246329

Johnson, M., MacLean, K., Reissig, C., Prisinzano, T., & Griffiths, R. (2011). Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum Drug and Alcohol Dependence, 115 (1-2), 150-155 DOI: 10.1016/j.drugalcdep.2010.11.005

Peet, M., & Baker, L. (2011). Salvinorin B derivatives, EOM-Sal B and MOM-Sal B, produce stimulus generalization in male Sprague-Dawley rats trained to discriminate salvinorin A Behavioural Pharmacology, 22 (5 and 6), 450-457 DOI: 10.1097/FBP.0b013e328349fc1b

Drug Enforcement Administration. SALVIA DIVINORUM AND SALVINORIN A (Street Names: Maria Pastora, Sage of the Seers,
Diviner’s Sage, Salvia, Sally-D, Magic Mint). December 2010.

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