Pharmacokinetics and Phenomenology of Inhaled Salvinorin A in Humans

Matthew Johnson, PhD

Authors: Matthew W. Johnson, Katherine A. MacLean, Chad J. Reissig, Michael J. Caspers, Thomas E. Prisinzano, Roland R. Griffiths

Abstract: Salvia divinorum is a plant with a long history of sacramental use among indigenous people of Oaxaca, Mexico. Salvinorin A, a kappa opioid agonist, has been identified as the principal psychoactive constituent of Salvia divinorum. Although traditional use of Salvia divinorum involves oral consumption of a tea, recent non-traditional use typically involves inhalation by smoking/vaporizing. In this completed study, the pharmacokinetics and subjective effects of inhaled salvinorin A were examined in six psychologically and physically healthy hallucinogen-using adults. Plasma samples were analyzed in triplicate via liquid chromatography-tandem mass spectrometry using a +5 mass analogue of salvinorin A as internal standard. Repeated measures regression showed salvinorin A levels were significantly (p < .01) associated with participant and monitor ratings of drug strength and monitor ratings of unresponsiveness, distance from usual daily reality and psychological distress. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and behavioral/subjective effects in humans. Results confirm the efficacy of a vaporization/inhalation technique for studying the effects of salvinorin A across multiple doses and across time.

Matthew W. Johnson, PhD is Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. Dr. Johnson is an expert in addiction and the behavioral and psychological effects of psychoactive drugs in humans. He has published human drug administration research with cocaine, nicotine, caffeine, various sedatives, and hallucinogens including psilocybin, dextromethorphan, and salvinorin A. In 2008, he published recommended safety guidelines for the re-emerging field of human hallucinogen administration research, and in 2011 the first placebo-controlled study of the psychoactive effects of salvinorin A in humans. In published research with psilocybin he has examined mystical-type effects, persisting changes in attitudes and behaviors, personality change, and psilocybin effects on headache. He is currently studying the effects of psilocybin on a meditation program, and psilocybin in the treatment of anxiety and depression among cancer patients. Dr. Johnson is also principal investigator of an ongoing pilot study examining the putative anti-addiction efficacy of psilocybin in the context of tobacco smoking cessation.

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