Dose-related effects of salvinorin A in humans: Dissociative, hallucinogenic, and memory effects

Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224-6823, USA, .
Psychopharmacology (Impact Factor: 3.88). 11/2012; 226(2). DOI: 10.1007/s00213-012-2912-9
Source: PubMed


Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A.
This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use.
Eight healthy hallucinogen-using adults inhaled up to 16 doses of salvinorin A (0.375–21 μg/kg) in ascending order. Physiological, behavioral, and subjective effects were assessed every 2 min for 60 min after administration. Qualitative subjective effects were assessed retrospectively via questionnaires at the end of sessions. Persisting effects were assessed 1 month later.
Orderly dose-related effects peaked at 2 min and then rapidly dissipated, replicating previous findings. Subjective effects were intense, with maximal drug strength ratings or unresponsiveness frequently observed at high doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale, Pharmacological Class Questionnaire) suggested some overlap with serotonergically mediated classic hallucinogens. Salvinorin A also produced dose-related dissociative effects and impairments in recall/recognition memory. At 1-month follow-up, there was no evidence of persisting adverse effects. Participants reported that salvinorin A effects were qualitatively different from other drugs.
Salvinorin A produces a unique profile of subjective and cognitive effects, including strong dissociative effects and memory impairment, which only partially overlap with classic hallucinogen effects. Along with nonhuman studies of salvinorin A, these results are important for understanding the neurobiology of the kappa opioid system and may ultimately have important therapeutic applications.

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Available from: Matthew W Johnson, Aug 11, 2014
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    • "Reports draw parallels with other drugs that act at the same receptor site as salvinorin A to suggest that salvinorin A has low addiction liability (Baggott et al., 2012; Ranganathan et al., 2012; Sumnall et al., 2012). But MacLean et al. (2013) warn of the potential for abuse because of the 'better experiences' with salvia compared to other drugs and the 'pleasant effects' (Casselman & Heinrich, 2011; Gonzalez et al., 2006). Four in five (79%) of drug-using students in the United Kingdom considered salvia and other new recreational drugs legal; three-quarters (74%) recognized that they were as risky as illicit drugs like ecstasy (Corazza et al., 2014). "
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    ABSTRACT: Salvia divinorum, a sage plant with leaves that can produce a psychoactive high, has been used for hundreds of years for its psycho-mimetic effects in religious rituals in South America. Salvia has now become popular mainly with adolescents and young adults for the short-lived relatively pleasant experiences many consider a ‘legal high’, and its ready availability through Internet purchases. The main (psycho)active compound in salvia is Salvinorin A, a potent ĸ-opioid agonist and although the short- and long-term effects have not been examined in sufficient detail, it is widely believed to have low addictive potential and low toxicity. Recent findings, however, seem to suggest that Salvinorin A can precipitate psychiatric symptoms and negatively affect cognition. Its ready availability and increasingly widespread use requires clinicians to have knowledge and awareness of its effects.
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    • "A mai napig alig van megbízható kontrollált humán tudományos vizsgálat ezen a téren. Mindössze két publikáció lelhető fel, az egyikben 10, a másikban 8 alanyt vizsgáltak, ez utóbbi egy hónapos utánkövetést is alkalmazott, aminek során nem tapasztaltak mellékhatásokat (MacLean et al., 2013; Ranganathan et al., 2012). A hatásokról az önkísérletezők beszámolói alapján van tudomásunk . "
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    • "; Perron et al . , 2012 ) . Carefully controlled studies in humans , initially experienced hallucinogen or Salvia divinorum users , characterized the effects of salvinorin A smoking ( 0 . 75 – 21 µg / kg ) . Salvinorin A ' s effects were of extremely rapid onset , peaked by 2 min after inhalation , and declined by 30 min ( Johnson et al . , 2011 ; MacLean et al . , 2013 ) . Under these carefully monitored conditions , volunteers reported robust hallucinogenic - like effects , depersonalization and derealization , but no robust dysphoria or aversion ( Johnson et al . , 2011 ) . It is unknown if effects in a different population ( i . e . , non - hallucinogen users ) would show a more robust dysphoria / "
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    ABSTRACT: Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.
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