Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans

Introduction

Salvia divinorum has been used historically in Mazatec shamanic practice and, more recently, has become a recreational psychoactive substance. Its principal psychoactive constituent, salvinorin A, is a kappa opioid receptor agonist that produces hallucinogenic effects distinct from classic serotonergic hallucinogens because it is not active at 5-HT2A receptors. Previous human pharmacokinetic data are limited and potentially incomplete: an earlier inhalation study measured plasma levels at only three post-inhalation time points that occurred well after the very rapid subjective peak observed in laboratory work, and differences in vaporisation techniques may have produced underestimates of typical plasma exposure from smoked or vapourised doses. Johnson and colleagues set out to characterise more precisely the time course of salvinorin A plasma levels after inhalation using a relatively efficient vapour-delivery method, and to relate those plasma levels to concurrent subjective and monitor-rated drug effects. The investigators also measured prolactin and cortisol, hormones known to respond to kappa agonists, and assayed residual drug remaining in the glass pipe to assess delivery efficiency. Frequent early blood sampling was used so that peak drug levels and their temporal relation to subjective effects could be examined directly.