Salvia divinorum, a plant native to southwest Mexico, has been traditionally used for inflammatory conditions and pain. Its main active component, salvinorin A (SA), is a potent hallucinogen that acts on κ opioid and cannabinoid type 1 receptors. Recent research has uncovered the cellular and molecular mechanisms behind SA's anti-inflammatory and analgesic effects. However, due to SA's short duration and hallucinogenic properties, current research aims to develop analogues that provide long-lasting pain relief and reduced inflammation without psychoactive effects. This review examines the roles of S. divinorum, SA, and its analogues, focusing on analgesic and anti-inflammatory properties while also addressing psychoactive effects.
An extract of Salvia divinorum reduced pain responses in rats with both neuropathic and inflammatory pain. The extract's analgesic effects were blocked by a kappa-opioid receptor antagonist, indicating a kappa-opioid mechanism. The extract also altered brain activity, increasing power spectral density in the anterior cortex and decreasing it in the posterior region, changes that may correlate with the hallucinogenic state seen in humans. The findings suggest Salvia divinorum could be a therapeutic alternative for chronic pain, acting through kappa-opioid receptors.