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

Abstract

Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

Keywords: Salvia divinorum; cortisol; endocrine; pharmacokinetics; prolactin; salvinorin A.

Fig. 1

The upper panel shows mean salvinorin A levels at all blood collection time points. The lower panel shows individual participant salvinorin A levels at each time point up to 30 min post-inhalation; individual participants are designated by different symbols. In both panels, the pre-inhalation assessment timepoint is shown at 0 min.

Fig. 2

Each panel shows individual participant salvinorin A plasma levels (left axis) and subjective rating of drug strength (right axis) for all time points in which both measures were assessed. Individual participants are designated by the same symbols shown in Fig 1. The pre-inhalation assessment timepoint is shown at 0 min.

Fig. 3

The upper panel shows mean prolactin levels at all blood collection time points. The lower panel shows individual participant prolactin levels at each time point up to 30 min post-inhalation; individual participants are designated by the same symbols shown in Fig 1; unconnected data points indicate a missing timepoint. In both panels, the pre-inhalation assessment time-point is shown at 0 min.

Fig. 4

The upper panel shows mean cortisol levels at all blood collection time points. The lower panel shows individual participant cortisol levels at each time point up to 30 min post-inhalation; individual participants are designated by the same symbols shown in Fig 1; unconnected data points indicate a missing time-point. In both panels, the pre-inhalation assessment timepoint is shown at 0 min.