The purpose of this study is to estimate nicotine uptake and assess subjective effects during ad libitum use sessions of 4 flavors of JUUL ENDS (also referred to as nicotine salt pod system; NSPS) products (i.e., Virginia Tobacco, Mint, Menthol and Mango) with 2 different nicotine concentrations. Subjective effects will also be assessed to gain an understanding of the user's experience during and after JUUL ENDS product use to evaluate the abuse liability of the products. The subject population will consist of healthy adult, male and female smokers, 21 to 65 years of age.

Inclusion Criteria:

1. Provides voluntary consent to participate in this study documented on the signed informed consent form (ICF).
2. Adult, male or female smoker, 21 to 65 years of age, inclusive, at screening.
3. Has been a smoker for at least 12 months prior to screening. Brief periods of non-smoking (e.g., up to ~7 consecutive days due to illness, quit attempt (prior to 30 days of screening), participation in a study where smoking was prohibited) during the 12 months prior to screening will be permitted at the discretion of the Investigator.
4. Currently smokes an average of 10 or more king size or 100s manufactured combustible cigarettes per day (CPD; non-menthol or menthol), as reported at screening.
5. Has a positive urine cotinine (≥200 ng/mL) at screening.
6. Has an exhaled CO (carbon monoxide) >10 ppm at screening.
7. A female subject of childbearing potential must have been using 1 of the following forms of contraception, and agree to continue using it through completion of the study: hormonal (e.g., oral, vaginal ring, transdermal patch, implant, or injection) consistently for at least 3 months prior to check-in (Day -1); double barrier method (e.g., condom with spermicide, diaphragm with spermicide) at screening; intrauterine device for at least 3 months prior to check-in (Day -1); a partner who has been vasectomized for at least 6 months prior to check-in (Day -1); abstinence beginning at least 6 months prior to screening.
8. A female subject of non-childbearing potential must be postmenopausal with amenorrhea for at least 1 year prior to check-in (Day -1) and follicle-stimulating hormone (FSH) levels consistent with postmenopausal status or have undergone one of the following sterilization procedures at least 6 months prior to check-in (Day -1): hysteroscopic sterilization; bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy.
9. Is willing to comply with the requirements of the study, including a willingness to use the study products during the study.

Exclusion Criteria:

1. Has a history or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2. Has a clinically significant abnormal finding on the physical examination, medical history, vital signs, ECG, or clinical laboratory results, in the opinion of an investigator.
3. Has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
4. Has had an acute illness (e.g., upper respiratory infection, viral infection) requiring treatment within 14 days prior to check-in (Day -1).
5. Has a fever (>100.5°F) at screening or check-in (Day -1).
6. Has a body mass index (BMI) >40.0 kg/m2 or <18.0 kg/m2 at screening.
7. Has a history of drug or alcohol abuse within 24 months of check-in (Day -1), as determined by an investigator.
8. Has or has a history of diabetes mellitus, asthma, or chronic obstructive pulmonary disease.
9. Has used prescription anti-diabetic medication and/or insulin therapy within 12 months prior to screening.
10. Has taken any medication for depression or asthma within 6 months prior to screening.
11. Has a systolic blood pressure <90 or >150 mmHg, diastolic blood pressure <40 or >95 mmHg, or heart rate <40 or >99 bpm at screening.
12. Has experienced an allergic reaction following previous e-cigarette use or with exposure to any primary components of the e-liquids (nicotine, flavor, benzoic acid, propylene glycol and glycerol).
13. Has an estimated creatinine clearance <70 mL/minute (using the Cockcroft-Gault equation) at screening.
14. Has a positive urine screen for alcohol or drugs of abuse at screening or check-in (Day -1).
15. If female, the subject is pregnant, has a positive pregnancy test at screening, is lactating, or intends to become pregnant during the time period from screening through the end of study.
16. Has used medications known to interact with cytochrome P450 (CYP) 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to check-in (Day -1).
17. Has used nicotine-containing products other than manufactured cigarettes (e.g., ENDS products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) within 30 days prior to check-in (Day -1).
18. Has any prior history of JUUL product use prior to screening.
19. Has used any prescription smoking cessation treatments, including, but not limited to, varenicline (Chantix®) or bupropion (Zyban®) within 3 months prior to check-in (Day -1).
20. Negative response (i.e., unwilling to use or unable to tolerate; e.g., experiences AEs (adverse events) during the product trial that will prevent the subjects from continuing to use the study products as judged by the investigator) to any of the JUUL products at screening.
21. Is a self-reported puffer (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).
22. Is planning to quit smoking during the study or postponing (within 30 days of screening) a quit attempt in order to participate in the study.
23. Has donated plasma within 7 days prior to check-in.
24. Has donated blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to check-in (Day -1).
25. Has participated in a previous clinical study for an investigational drug, device, biologic, or tobacco product within 30 days prior to check-in (Day -1).
26. Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee of the study site.
27. Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee, shareholder, or is member of the board of directors of JUUL Labs, Inc.
28. In the opinion of the Investigator, the subject should not participate in this study.
29. Has previously taken part in, has been excluded or withdrawn from, or has completed this study.

The study is open label; however, subjects will be masked to the percentage of nicotine in JUUL products.