The neuropharmacological assessment of Salvia divinorum Epling and jativa-m

Salvia divinorum (SD) has been used by the native peoples of Oaxaca Mexico as a shamanistic entheogen for numerous generations. First stumbled on scientifically in 1952 when psychoactive mushrooms of the area were being studied, this member of the mint family became an interesting side note in ethnobotanical studies. Over thirty years later the main active ingredient salvinorin A (SA) was identified as the first non-nitrogenous hallucinogen known. After a short time the list of firsts for this plant grew as the pharmacological activity of salvinorin A was defined as a selective kappa opioid receptor (KOR) agonist. In the years to follow certain uses of the plant seemed to contradict the selectivity of salvinorin A. In case reports from Australia, Salvia divinorum was shown to have antidepressant activity in refractory depression patients when given quids made up of the leaves of Salvia divinorum. From numerous studies of KOR agonists showing the depressive effects on monoamine levels in the CNS the use of the plant should cause an exacerbation of symptoms in depressive individuals.;It was with these conclusions in mind that this dissertation project was started. To understand or elicit differences in action of Salvia divinorum and salvinorin A when given in formulations that tie in a metabolic element, and more closely mimic extraction methods seen in quids, and the traditional metate preparation of the Mazatec peoples.;The results of this were the characterization of an antidepressant-like activity in the salvia water extract (SWE) when given orally at a concentration of 50mg/kg in the forced swimming test (FST) and tail suspension test (TST). The corollary motor activity test, the open field test (OFT), showed no significant changes in locomotor activity. The main psychoactive compound salvinorin A, when giving i.p., expressed dopaminergic activity in a dose dependent manner that could not be explained via the kappa opioid system. This shows that when testing for pharmacological activity of a plant great care and planning should be taken to characterize activity with formulations that closely resemble those used in human consumption.