Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans
This double-blind, randomised controlled trial (n=10) assessed the behavioural, subjective, cognitive, psychophysiological and endocrine effects of Salvia divinorum (0, 8 and 12 mg) in healthy participants. Salvia produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power, but did not produce euphoria, cognitive deficits or changes in vital signs. Overall, Salvia was well tolerated.
Authors
- Deepak Cyril D’Souza
- Andrew Sewell
- Brian Pittman
Published
Abstract
Background
Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA), a highly selective agonist at the kappa opiate receptor (KOR), is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans.
Methods
In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioural, subjective, cognitive, psychophysiological and endocrine effects of 0 mg, 8 mg and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia.
Results
SA produced psychotomimetic effects and perceptual alterations including dissociative and somaesthetic effects, increased plasma cortisol and prolactin and reduced resting EEG spectral power. SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits or changes in vital signs. The effects were transient and not dose-related. SA administration was very well tolerated without acute or delayed adverse effects.
Conclusions
SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with KOR agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, elucidate the underlying mechanisms involved and explore the basis for individual variability in its effects.
Research Summary of 'Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans'
Introduction
Salvia divinorum and its principal psychoactive constituent, salvinorin A (SA), have become increasingly used recreationally, particularly by adolescents and young adults. SA is a highly potent, selective kappa opioid receptor (KOR) agonist and, unlike many classical hallucinogens, lacks activity at dopaminergic, serotonergic or NMDA receptor systems. The human literature up to the time of this study consisted mainly of anecdotal reports and a small number of experimental investigations that were limited by uncontrolled designs, sublingual administration with poor bioavailability, small samples, or use of Salvia leaf preparations rather than defined doses of pure SA. Important gaps remained regarding SA’s pharmacokinetics in humans and its objective behavioural, subjective, cognitive, endocrine and psychophysiological effects under controlled conditions. B. and colleagues set out to characterise comprehensively the acute effects and safety of inhaled SA in healthy human volunteers with prior Salvia exposure. The study aimed to measure dose-related subjective and behavioural effects, cognitive performance, resting EEG, plasma SA and its major metabolite salvinorin B (SB), and neuroendocrine responses (cortisol and prolactin) using a double-blind, randomised, placebo-controlled, counterbalanced crossover design. The authors framed the work as addressing prior methodological limitations by using pure SA, objective biological measures and standardised delivery in the laboratory.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Ranganathan, M., Schnakenberg, A., Skosnik, P. D., Cohen, B. M., Pittman, B., Sewell, R. A., & D'Souza, D. C. (2012). Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans. Biological Psychiatry, 72(10), 871-879. https://doi.org/10.1016/j.biopsych.2012.06.012
References (2)
Papers cited by this study that are also in Blossom
Johnson, M. W., Maclean, K. A., Reissig, C. J. et al. · Drug and Alcohol Dependence (2011)
Riba, J., Anderer, P., Morte, A. et al. · British Journal of Clinical Pharmacology (2002)
Cited By (3)
Papers in Blossom that reference this study
Hernández-Alvarado, R. B., Madariaga-Mazón, A., Ortega, A. et al. · ACS Chemical Neuroscience (2020)
Steeds, H., Carhart-Harris, R. L., Stone, J. M. · Therapeutic Advances in Psychopharmacology (2014)
Maclean, K. A., Johnson, M. W., Reissig, C. J. et al. · Psychopharmacology (2012)
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