CEREBELLUM AND ENDOCANNABINOID RECEPTORS: A NEW NEUROBIOLOGICAL LINK FOR MITRAGYNINE (MITRAGYNA SPECIOSA KORTH) ABUSE LIABILITY

?Drug abuse is a major concern worldwide and has remained so for decades. Beside synthetic drugs, the misuse of psychoactive compounds from natural products as drugs of abuse contributes to this incessant concern. Reports on misuse of mitragynine, an alkaloid from the plant Mitragyna speciosa Korth (Kratom or Ketum) as a substituent for opioid withdrawal syndrome are becoming prevalent in recent years, and extended beyond the geographical boundaries of the plant. Although there are comprehensive data available on chemical and pharmacological properties of mitragynine particularly on its opioid-like analgesic property, the mechanism of actions for its abuse liabilities remain unclear. This article presents the plausible leads for mitragynine abuse liability by reviewing the established roles of endocannabinoid system as a molecular target where the opioids and cannabinoids act. These leads build for the arguments to posit the involvement of ubiquitous endocannabinoid receptors within the cerebellum and the evidences for cerebellar non-motor functions (brain reward processes, drug-induced long term memory and plasticity, and structural alterations linked to addiction) towards a potential new player as the basis for abuse liability of Kratom, accumulating to addiction.