Synthetic Drugs and Their Effects on Lipid Metabolism and Endocannabinoid Signalling; a Review Article.

Synthetic drugs, particularly synthetic cannabinoids and stimulants, have emerged as potent psychoactive substances with significant impacts on human physiology, notably lipid metabolism. These drugs, often engineered to evade detection and regulation, interact with cellular systems in unpredictable and sometimes harmful ways. This review explores the classification, pharmacokinetics, metabolic pathways, and lipid-related effects of synthetic drugs. Emphasis is placed on the endocannabinoid system, a crucial regulator of lipid metabolism, neuroinflammation, and synaptic plasticity. Synthetic cannabinoids (SCs), such as JWH-018 and AM-2201, exhibit high affinity for CB1 and CB2 receptors and disrupt endogenous lipid signaling, contributing to altered lipid homeostasis and potential metabolic dysregulation. Their metabolism involves complex biotransformations in the liver via cytochrome P450 enzymes, with metabolic byproducts often more toxic than the parent compounds. Studies in human liver microsomes, hepatocytes, and in vivo models highlight interspecies metabolic variability and the limitations of current in vitro models. The co-administration of cannabinoids with lipid-based formulations has been shown to enhance lymphatic absorption, suggesting a dual role for lipids in drug delivery and metabolic impact. Understanding these biochemical interactions is critical for developing therapeutic strategies and regulatory policies to mitigate the health risks associated with synthetic drug abuse.