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bupropion + zonisamide is an investigational drug combination being developed by Rose Research Center, LLC for smoking cessation, specifically to aid smokers in transitioning from combustible cigarettes to electronic cigarettes (e.g., JUUL). The combination consists of bupropion, an FDA-approved antidepressant and smoking cessation aid that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI) and a non-competitive antagonist of nicotinic acetylcholine receptors, and zonisamide, an FDA-approved anticonvulsant that modulates voltage-gated sodium and T-type calcium channels. By targeting multiple pathways involved in nicotine addiction and withdrawal—including the dopaminergic reward system and neuronal excitability—the combination is intended to reduce cravings and the reinforcing effects of smoking more effectively than either agent alone. The treatment is currently being evaluated in Phase 3 clinical trials where it is administered alongside ad libitum e-cigarette use.
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