Inclusion Criteria:
* Male or female subjects, age ≥18 years.
* Test positive for cotinine using a point-of-care Oral Fluid Screening Device (OFD) with positive detection at ≥30 ng/mL cotinine.
* Current daily nicotine-containing electronic cigarette usage as recorded in a screening diary for at least 7 consecutive days. Willing to bring the e-cigarette or nicotine device used to the clinical site so that the specific product type, flavor, and nicotine level can be documented.
* Failed at least one previous attempt to stop vaping with or without therapeutic support.
* Willing to initiate study treatment on the day after randomization and set a quit date within Day 7 and Day 14.
* Willing to actively participate in the study's vaping cessation behavioral support provided throughout the study.
* Able to fully understand study requirements, willing to participate, and comply with dosing schedule.
* Sign the Informed Consent Form.
Exclusion Criteria:
* Currently smoking or having smoked within 3 months prior to study randomization, any combustible cigarettes, other combustible tobacco products or non-combustible tobacco products such as heat not burn products or nicotine pouches (ie, dual users).
* Currently smoking/vaping cannabis or having smoked or vaped cannabis within 4 weeks (28 days) prior to study randomization or planned use while on study. Other methods of cannabis consumption, eg, edibles, tinctures, capsules, topicals, etc. are allowed.
* Expired Carbon Monoxide (CO) levels ≥6 ppm, indicating recent combustible tobacco or cannabis smoking.
* A score of 0-3 on the Penn State e-Cigarette Dependence Index indicating no dependence.
* More than 1 study subject in same household during the study treatment period.
* Known hypersensitivity to any of the excipients, previous cytisinicline treatment in a prior clinical study, or any previous use of cytisinicline.
* Positive urinary drugs of abuse screen determined within 28 days before the first dose of study drug. (Note: Although THC is part of the standard drug screen, it is not necessarily exclusionary. Refer to exclusion criteria #2).
* Clinically significant abnormal serum chemistry or hematology values, as determined by the investigator, within 28 days of randomization.
* Clinically significant abnormalities on screening visit 12-lead ECG, as determined by the investigator, after minimum of 5 minutes in supine position within 28 days of randomization.
* Recent history (within 3 months prior to screening) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
* Current uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
* Currently psychotic or having had a psychotic event in the 3 months prior to the screening visit. If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits.
* Currently having suicidal ideation or risk for suicide (YES to either question 3, 4 or 5 OR YES to any suicidal behavior question on the C-SSRS with clear suicidal intent or suicide attempt within the last 10 years).
* Current symptoms of moderate to severe depression (depression score ≥11 using depression questions on the Hospital Anxiety and Depression Scale \[HADS\] at screening visit).
* Renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min at screening visit (estimated with the Cockroft-Gault equation and reported by the central laboratory).
* Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN) at screening visit.
* Recent history or symptoms (within 4 weeks of randomization) of unstable respiratory disease (eg, pneumonia, product-use associated lung injury or EVALI, etc).
* Women who are pregnant or breast-feeding.
* Female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study. Acceptable methods of birth control include:
* True abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
* Barrier methods:
* diaphragm
* cervical cap
* contraceptive sponge
* intrauterine device (IUD)
* double barrier method (condom with spermicide)
* Hormonal methods:
* Oral contraceptives
* Vaginal ring such as NuvaRing
* Skin patch such as Xulane
* Injection such as Depro-Provera
* Implantable rod such as Nexplanon
* Intrauterine device (IUD)
* Participation in a clinical study with an investigational drug or biologic in the 4 weeks prior to study randomization.
* Use of any smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy \[NRT\]) in the 4 weeks prior to study randomization or planned use of these or other nicotine replacement medications during the study.
* Any planned use during the study of combustible cigarettes or other nicotine-containing, non-vaping products (eg, pipe tobacco, cigars, snuff, smokeless tobacco, hookah, ZYN pouches, etc).
* Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
