This open-label study (n=6) investigated the effects of vaporized Salvinorin A (1.26mg or 1.47mg/70kg) with regard to the pharmacokinetic time course of its availability in plasma concentration, subjective intensity ratings, and downstream hormonal effects. Results indicated that is plasma concentration and intensity of drug effects peaked at 2 minutes after inhalation. Salvinorin A increased prolactin (a hormone) 5 minutes after inhalation, whereas cortisol (another hormone) concentration was inconsistent and not well correlated with drug levels.
Abstract
“Introduction: 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.
Method: 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.
Results: 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.
Discussion: 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.”
Authors: Matthew W. Johnson, Katherine A. MacLean, Michael J. Caspers, Thomas E. Prisinzano & Roland R. Griffiths
Summary
Introduction
Salvia divinorum, a plant in the mint family, has been used in shamanic practices of the Mazatec people of Oaxaca, Mexico for at least several hundred years. It has gained increased popularity as a psychoactive drug in non-traditional contexts.
Salvinorin A’s pharmacokinetic profile in humans may inform the understanding of potential adverse reactions observed in recreational use of S. divinorum, and may also help with the development of new treatments for neurological, pain, mood, personality, gastrointestinal, and cocaine-use disorders.
Salvinorin A, a kappa opioid agonist, was inhaled by six healthy adults. Blood samples were collected at 13 time points up to 90 min post-inhalation, and drug levels were significantly, positively correlated with participant and monitor drug effect ratings.
Studies of inhaled salvinorin A may have limited relevance for potential therapeutic applications, but may inform the relation between plasma drug levels and resulting subjective effects at play in potential therapeutic applications.
Studies in rats and monkeys have provided basic pharmacokinetic data, but these findings may not apply to humans. One previous study assessed the pharmacokinetic profile of salvinorin A in humans, but it did not examine the relation between individual salvinorin A pharmacokinetic and psychoactive effects, and it used a commercial vaporizer to deliver a maximum dose that was eight to twelve times higher than the maximum dose in previous studies.
In this study, we examined the time course of salvinorin A plasma levels after inhalation of a high dose, delivered via a relatively efficient vaporization system.
Participants
Participants were 6 individuals who had taken part in up to 20 previous sessions without collecting blood samples. Two individuals were excluded from the study due to subjective and cognitive data being included in the previous study.
Six participants, with a mean age of 25 years, used S. divinorum on a mean of 11 previous occasions, and had used classic hallucinogens on a mean of 32 previous occasions.
Procedure
Each participant inhaled a single high dose of vaporized salvinorin A. Blood samples were collected at 13 time points and analyzed by liquid chromatography-tandem mass spectrometry using a +5 mass analogue of salvinorin A as the internal standard. Residual salvinorin A was determined in the glass pipe by washing with dichloromethane and drying under a stream of nitrogen.
Data analysis
We calculated Pearson’s correlations between drug levels and hormone levels, and between drug levels and subjective and monitor ratings of drug effects, using only the 7 time points when both blood and ratings were collected.
Repeated measures regression was used to model the relationship between salvinorin A plasma level and participant and monitor ratings of drug effects.
Results
Salvinorin A levels peaked at 2 min post-inhalation, and then decreased rapidly and gradually until 90 min post-inhalation, when levels were close to baseline. Individual participant variations occurred, with peak effects occurring as early as 1 min to as late as 4 min post-inhalation.
The relationship between drug blood levels and subjective drug strength was illustrated by the correlation between plasma levels and subjective drug strength, and the effect of salvinorin A level on participant and monitor ratings of drug strength, distance from usual daily reality, unresponsiveness, psychological distress, and paranoia.
Salvinorin A administration increased plasma prolactin levels and decreased plasma cortisol levels. However, there was substantial individual variability with little evidence of a cortisol response observed in some participants.
Individual participant correlations between hormone levels and physiological measures were not significant, and there was no significant relation between salvinorin A levels and prolactin levels, cortisol levels and prolactin levels, or cortisol levels and salvinorin A levels at the group level.
Discussion
This study examined salvinorin A plasma levels after inhalation, and found novel information relevant to three domains.
Drug delivery
The present study showed that a dose of 18.8 mg/kg of salvinorin A resulted in a plasma level of 18.8 ng/mL at peak effects, which suggests that the delivery system used in this study was substantially more efficient.
Time course of salvinorin A blood levels
The present study found a strong correlation between salvinorin A levels and ratings of drug strength throughout the time course. This finding is consistent with previous studies in rhesus monkeys.
Time course and magnitude of hormonal response
Similar to Ranganathan et al. (2012), the present study showed increases in prolactin and cortisol following salvinorin A administration, but the hormone responses followed a more delayed and prolonged time course.
Conclusion
This study confirmed that vaporization of Salvinorin A results in higher drug plasma levels compared to smoking. It also showed strong correlations between salvinorin A blood levels and drug strength ratings across the time course of drug effects.