Salvinorin A in humans: A systematic review of pharmacokinetics, pharmacodynamics, and safety.

Abstract

Salvinorin A, the principal psychoactive constituent of <i>Salvia divinorum</i>, is a highly selective κ-opioid receptor agonist and a rare example of a κ-opioid receptor-mediated psychedelic drug. Preclinical work of salvinorin A has shown promising effects in neuropsychiatric animal models. However, human studies remain heterogeneous and fragmented, highlighting the need for synthesis. Thus, we conducted a systematic review to synthesize available human studies of salvinorin A, with a focus on pharmacokinetics, pharmacodynamics, safety, and longer-term effects. We searched PubMed, Web of Science, and EMBASE from inception to January 18, 2026. We included 12 clinical trials comprising 174 participants. Most studies enrolled medically healthy, hallucinogen-experienced volunteers and administered salvinorin A by inhalation (0.375-21 µg/kg or 0.2-12 mg). Pharmacokinetic profiles were characterized by rapid onset within seconds, peak effects at 1-2 minutes, and resolution within 30 minutes, consistent with fast absorption and clearance. Sublingual administration in two studies produced slower onset and longer duration, whereas oral dosing was inactive in one study. No serious adverse events were reported. Physiological parameters were largely stable, with occasional mild increases in blood pressure/heart rate. Acute psychological effects included disorientation, anxiety, and distress in subsets of participants, alongside reports of positive subjective changes. Long-term adverse effects were rare, and abuse potential appeared low. Overall, salvinorin A exhibits a distinct human neuropsychopharmacological profile compared with serotonergic psychedelics. These findings support cautious further investigation in controlled studies. Further, salvinorin A can serve as a model for probing κ-opioid receptor-mediated alterations of consciousness in humans.

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