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

Abstract

RationaleSalvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant.ObjectivesThe objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels.MethodsSublingual 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.ResultsNo 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).ConclusionsOur 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.

Acute and post-acute behavioral and psychological effects of salvinorin A in humans

“…These first two reports provide almost no information on demographics of participants and little information on administration procedures and either behavioral or subjective effects of SA. Mendelson et al (2010) did not obtain any psychoactive effects in eight participants, presumably due to the unreliable nature of sublingual absorption of SA. Finally, Johnson et al (2010) completed a placebocontrolled dose-response study of inhaled SA in four participants, focusing on vital signs and objective measurements, of inebriation and briefly describing some subjective effects.…”

“…divinorum contains a potent psychoactive which facilitates hallucinogenic states of consciousness under controlled conditions. Using safe and ethical research procedures (Johnson et al 2010;Mendelson et al 2010;Pichini et al 2005;Siebert 1994), the immediate and lasting effects of SA can be assessed.…”

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

“…Mendelson et al (2010) aimed to thoroughly investigate the effect of salvinorin A when administered sublingually. This placebo-controlled study examined the subjective effects (Subjective Drug Effects Questionnaire, Altered States of Consciousness Questionnaire, and Positive and Negative Affect Schedule) and physiological effects (heart rate, blood pressure, O 2 saturation, and body temperature) of an ascending dose (0 -4000 g sublingual) of salvinorin A solvated in 25% DMSO/75% polyethylene glycol.…”

Naturally occurring furanoditerpenoids: distribution, chemistry and their pharmacological activities

“…Salvinorin A (122), a compound isolated from Salvia species, has Phytochem Rev been proved to have KOR affinity (Munro et al 2005). While a recent study showed sublingual dose up to 4 mg salvinorin A did not produce significant greater physiological or subjective effects than placebo (Mendelson et al 2011). The results suggested that the sublingual bioavailability of salvinorin A is low.…”