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Motivations: \u201cKnow the potential enemy at an individual level.\u201d Smoking or vaping produces an initial \u201cbolus\u201d of nicotine in the blood and brain, lasting ~5 minutes with a peak concentration of ~100\u2013200\u00a0nM. The bolus largely governs reinforcement, reward, and cognitive enhancement. A prolonged declining phase of [nicotine], with a half-time of 1\u20134 hours, largely suppresses withdrawal symptoms and governs the known cell biology of addiction. Next, \u201cKnow the potential therapy,\u201d because individual [nicotine]t records will be useful during research on the effectiveness of nicotine replacement therapy. Finally, \u201cKnow the physiology.\u201d The only three known effects on nAChRs in cerebrospinal fluid at the relevant [nicotine]t are activation, desensitization, and chaperoning\/upregulation. Therefore, additional mechanistic insights will arise from correlating [nicotine]t with readily measurable physiological data on those effects in molecular, cellular, and brain slice systems and animal models. Interstitial fluid is the appropriate compartment for a CNM. The molecular sensor technology could employ fluorescence, as shown by progress on measuring [nicotine]t with improved variants of intensity-based nicotine-sensing fluorescent reporters (iNicSnFRs). Electrochemical measurements of [nicotine]t may also be possible. Studies like the Population Assessment of Tobacco Health would contextualize [nicotine]t measurements during each subject\u2019s ad libitum nicotine intake, hopefully at a cost &amp;lt;$100 for a 24-hour record.<\/jats:p>","DOI":"10.1093\/ntr\/ntaf062","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:25:51Z","timestamp":1741710351000},"page":"1499-1512","source":"Crossref","is-referenced-by-count":4,"title":["Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9341-0049","authenticated-orcid":false,"given":"Aaron L","family":"Nichols","sequence":"first","affiliation":[{"name":"Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher 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