Methamphetamine (METH) is a highly addictive illicit psychostimulant with a significant annual fatality rate. Emerging studies highlight its role in neuroinflammation and a range of neurological disorders. This review examines the current landscape of potential drug targets for managing neuroinflammation in METH use disorders (MUDs), with a particular focus on the rationale behind targeting Toll-like receptor 4 (TLR4), the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and other promising targets. Given the multifactorial neurological effects of METH, including cognitive impairment and neurodegeneration, addressing METH-induced neuroinflammation has shown considerable promise in partially mitigating the damaging effects on the central nervous system and improving behavioral outcomes. This article provides an overview of the existing understanding while charting a promising path forward for developing innovative MUD treatments, focusing on neuroinflammation as a therapeutic target. Targeting neuroinflammation in METH-induced neurological disorders shows significant promise in mitigating cognitive impairment and neurodegeneration, offering a potential therapeutic strategy for improving outcomes in MUD. While challenges remain in optimizing treatments, ongoing research into combination therapies, novel drug delivery systems, and neuroprotective agents suggests a positive outlook for more effective interventions.
Keywords: Methamphetamine; NLRP3; TLR-4; neuroinflammation; neurological disorders; use disorders.