Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A

Salvinorin A is a unique hallucinogen that is seeing increased use in humans. It is not currently a controlled substance and is used as a legal alternative to controlled substances. Usually smoked or buccally absorbed by chewing, doses of approximately 200 mcg can produce profound hallucinogenic effects of short duration. The mechanism of action of salvinorin A is at the kappa-opioid receptor. Little data is available on the medical effects of this substance so animal studies were undertaken to explore the acute toxic effects of this substance in rats and the chronic effects in mice. Rats were anesthetized and administered salvinorin A at 1600 mcg/kg or vehicle. Recordings were made of galvanic skin response, EKG, temperature, and pulse pressure for 100 minutes. Mice were chronically exposed to vehicle or 400, 800, 1600, 3200, or 6400 mcg/kg of salvinorin A for two weeks. After exposure the animals were sacrificed and brain, heart, kidney, bone marrow, blood and spleen were removed, fixed, sectioned, stained and examined by light microscopy. No effects were seen on cardiac conduction, temperature, or galvanic skin response. A nonsignificant rise was seen in pulse pressure. Histologic studies of spleen, blood, brain, liver, kidney, and bone marrow did not find any significant histologic changes at any of the doses examined. These data suggests that the toxicity of salvinorin A is relatively low, even at doses many times greater than what humans are exposed to. However, further studies should be done on blood pressure effects. The psychological impact of this potent hallucinogen should also be investigated.