An Updated Review On Buprenorphine And Methadone: Efficacy, Safety And Clinical Innovations

Heroin, a semi-synthetic opioid derived from morphine, remains one of the most addictive and socially destructive substances worldwide. Its misuse contributes significantly to global morbidity, mortality and economic burden. The evolving understanding of opioid use disorder (OUD) has shifted its perception from moral failing to a complex neurobehavioral disease characterized by compulsive drug-seeking and neuroadaptive changes in brain circuits. Effective management of OUD relies on medication-assisted therapy (MAT), primarily involving buprenorphine and methadone, alongside psychosocial interventions. Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, offers a unique therapeutic profile with a ceiling effect on respiratory depression, reducing overdose risks. Its transdermal, sublingual and depot formulations have improved adherence and minimized diversion potential. In contrast, methadone, a full μ-opioid receptor agonist and NMDA receptor antagonist, provides a stronger treatment retention and analgesic potency but demands careful titration due to cardiotoxicity and variable metabolism influenced by CYP polymorphisms. Recent advances in structure-activity relationship (SAR) studies, pharmacogenomics and green synthesis have expanded the therapeutic scope of both agents. Comparative analysis shows buprenorphine’s superiority in safety and outpatient flexibility, while methadone remains indispensable for severe dependence. Future-oriented strategies such as micro-induction protocols, pharmacogenomics-guided dosing, digital adherence tools and integration of herbal adjuncts are reshaping OUD therapy into a more personalized and sustainable model. This review consolidates current evidence, pharmacological insights and translational innovations, underscoring how buprenorphine and methadone continue to redefine the landscape of addiction medicine.