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**Nicotine + cytisine** is a combination of two agents used in smoking cessation. **Nicotine** acts as an agonist of nicotinic acetylcholine receptors, providing nicotine replacement therapy (NRT) to reduce withdrawal symptoms and cravings during smoking cessation. **Cytisine** is a plant-derived alkaloid that acts as a partial agonist at the α4β2 nicotinic acetylcholine receptor, reducing nicotine cravings and withdrawal, and acts as an antagonist by blocking nicotine from binding fully to these receptors. The combination approach is under clinical investigation and is hypothesized to offer additive or complementary benefits by leveraging both receptor activation (via nicotine) and partial agonism/blockade (via cytisine), potentially improving smoking abstinence rates in individuals attempting to quit. The combination is being specifically studied in trials that pair cytisine with nicotine salt e-cigarettes as a version of short-acting NRT[3].
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