Opioid receptors and legal highs: Salvia divinorum and Kratom

Salvia divinorum and Mitragyna speciosa ("Kratom"), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the major alkaloid identified from Kratom, has been reported as a partial opioid agonist producing similar effects to morphine. An interesting minor alkaloid of Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported to activate supraspinal mu- and delta- opioid receptors, explaining their use by chronic narcotics users to ameliorate opioid withdrawal symptoms. Despite their widespread Internet availability, use of Salvia divinorum and Kratom represents an emerging trend that escapes traditional methods of toxicologic monitoring. The purpose of this article is to familiarize toxicologists and poison control specialists with these emerging psychoactive dietary supplements.