Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action

Introduction

Salvia divinorum is a herbal plant from southwestern Mexico long used in Mazatecan medical and religious practice. Traditional preparations have been applied to ailments that overlap with inflammatory conditions and pain such as headaches, gastrointestinal complaints and rheumatism, while modern extracts with elevated salvinorin A concentrations are widely used recreationally for their potent, short-lived hallucinogenic effects. Phytochemical work has identified a series of neo-clerodane diterpenes (salvinorins A–F), with salvinorin A (SA) the dominant active component; pharmacological screening shows SA is a high-affinity agonist at κ opioid receptors (KORs) and modulates cannabinoid type 1 (CB1) receptors, but lacks action at the classical 5-HT2A serotonin receptor targeted by psilocybin and LSD. This review aims to synthesise available evidence on S. divinorum, SA and semi-synthetic analogues with emphasis on analgesic and anti-inflammatory effects, while also describing psychoactive properties and safety signals. Coffeen and Pellicer focus mainly on preclinical pharmacology, mechanistic biochemical data, animal models of inflammation and pain, and early reports in humans and poison-control data to consider therapeutic potential and remaining translational challenges.