Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial.

Salvinorin A (SA), the psychoactive compound in the hallucinogenic plant Salvia divinorum, was administered sublingually at doses up to 4 mg to eight experienced users in a placebo-controlled ascending-dose study. No dose produced significantly greater physiological or subjective effects than placebo, and the effects did not resemble those of smoked Salvia divinorum. SA was detectable in plasma and urine but mostly below the reliable quantification limit of 0.5 ng/mL. The results suggest that sublingual bioavailability of SA is low, indicating that higher doses, alternate formulations, or other routes of administration are needed to study its effects in humans.

Study at a glance

Abstract

Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant. The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels. Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design. No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported "typical" effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL). Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.