Dose-related Behavioral, Subjective, Endocrine and Psychophysiological Effects Of the Kappa Opioid Agonist Salvinorin A in Humans
Cohen, B., D’Souza, D. C., Pittman, B. P., Ranganathan, M., Schnakenberg, A., Sewell, R. A., Skosnik, P. D.
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.
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.