Johnson · Drug and alcohol dependence 2011 · double-blind placebo-controlled ascending-dose crossover trial · n=4

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

Cited 137 times in the scientific literature.

Level 2 - randomized trial

Individual double-blind, placebo-controlled randomized crossover trial.

PubMed 21131142 · doi:10.1016/j.drugalcdep.2010.11.005 · record verified 2026-08-30

What was done

A double-blind, placebo-controlled study evaluated the pharmacological and subjective effects of inhaled salvinorin A in 4 physically and psychologically healthy adults with prior hallucinogen use. Across separate sessions under comfortable and supportive conditions, participants inhaled 16 ascending doses of salvinorin A (ranging from 0.375 μg/kg to 21 μg/kg) and 4 intermixed placebo doses. Drug strength ratings were recorded every 2 minutes for 60 minutes post-inhalation. Subjective experiences were assessed using the Mysticism Scale, the Hallucinogen Rating Scale, and participant narratives; physiological effects were assessed via heart rate and blood pressure monitoring.

What was found

Inhaled salvinorin A produced orderly time- and dose-related subjective effects that peaked rapidly at 2 minutes post-inhalation and resolved by approximately 20 minutes. Dose-related increases occurred on the Mysticism Scale and Hallucinogen Rating Scale. Salvinorin A did not significantly alter heart rate or blood pressure (exact numerical values were not reported in the abstract). Participant narratives reported intense vestibular and interoceptive alterations (such as changed spatial orientation and bodily pressure), recurring themes of childhood memories, cartoon-like imagery, and contact with entities.

Why it matters

This trial provides human laboratory evidence that selective kappa opioid receptor agonism produces a rapid-onset, short-acting profile of mystical-type and hallucinogenic effects without marked cardiovascular changes.

Limits

The study had an extremely small sample size (n = 4), which substantially limits statistical power and precision. The population was restricted to experienced hallucinogen users in a highly supportive setting, limiting generalizability to drug-naive individuals or uncontrolled recreational contexts. Numerical cardiovascular values and effect sizes were omitted from the abstract.

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