Twenty-four healthy participants were included in this placebo-controlled, randomized, double-blind study investigating the involvement of kappa-opioid receptor and serotonin-2A agonism in effects induced by salvinorin-A. Participants were divided into two groups receiving four pretreatment (placebo or naltrexone [group 1] or ketanserin [group 2]) and treatment (placebo or 1mg vaporized salvinorin-A) combinations over four sessions with a washout period of 7 days between sessions. Psychological effects were captured using the Hallucinogen Rating Scale (HRS), the Altered States of Consciousness (APZ) questionnaire and the State-Trait Anxiety Inventory (STAI). Peak drug effects were assessed using a Visual Analogue Scales (VAS). Cardiovascular effects were measured using blood pressure and heart rate, and neuroendocrine effects were assessed by measuring cortisol, prolactin and growth hormone levels. Plasma concentrations and pharmacokinetic parameters were also identified. Salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. Peak drug effects were identified 1 and 2 minutes after dosing. These effects were blocked by naltrexone, but not by ketanserin.