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A1-These are proven meds to quit smoking. They stimulate brain nicotinic acetylcholine receptors (nAChR). Varenicline and cytisine are selective partial agonists (stimulate + block) of α4β2 type nAChR, key for nicotine addiction. NRT stimulates all nAChR types. #AskGeneticsSRNT

A2.2 In our St PETER HIV RCT, we tested 4 groups: 1:ActiveVar+P-NRT, 2:P-Var+Active NRT, 3:Active Cyt+P-NRT, 4:P-Cyt+ActiveNRT for alcohol use (primary endpt) and smoking (2ndary endpt). Alcohol reduction (and abstinence) was high in all groups at 3, 6, 12 m. #AskGeneticsSRNT

A2.3 In St PETER HIV RCT, smoking cessation rates were similar in all 4 treatment arms. Results underscore that varenicline and cytisine (and NRT) can be used successfully in people with HIV+ comorbidities (HCV, dep, OUD) and may also help reduce alcohol use. #AskGeneticsSRNT

A4: Nicotine in both cigarettes and NRT derives from tobacco plants, but NRT is purified, so FREE of tar and ~7,000 chemicals (~200 cancer causing) in cigarette smoke. NRT has far lower addiction potential than cigarettes due to slower rise in blood nic levels. #AskGeneticsSRNT

A6.1: α4β2-type nicotinic acetylcholine receptors (nAChR) are sub-type most strongly linked to nicotine dependence. They are ubiquitous in the brain and midbrain (“dopamine reward system”). Varenicline and cytisine are selective partial agonists of α4β2 nAChRs. #AskGeneticsSRNT

A6.2: α4β2-type nAChRs are cell surface receptors on cell bodies of dopamine neurons in ventral tegmental area (VTA) which project to nucleus accumbens (NA) + cortex, releasing dopamine. Varenicline, cytisine, and NRT bind α4β2 nAChRs, reducing nicotine craving. #AskGeneticsSRNT