This is an observational, crossover design that will examine the pharmacokinetics and pharmacodynamics of impact of smoking tobacco cigarettes or vaping the JUUL electronic cigarette.

The goal of this study is to better understand the pharmacokinetic and pharmacodynamics responses produced by the JUUL e-cigarette, compared to tobacco cigarettes, in e-cigarette and tobacco cigarette smokers.

Specific Aim #1- To categorize the nicotine pharmacokinetic (PK) profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve) and compare when using the JUUL e-cigarette vs. a tobacco cigarette in a standardized manner.

Specific Aim #2- To categorize the nicotine PK profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve(AUC)) and compare when using the JUUL e-cigarette vs a tobacco cigarette when using the product ad libitum.

Specific Aim #3- To evaluate various outcomes following JUUL e-cigarette or tobacco cigarette use, both with standardized and ad lib use including: heart rate, plasma catecholamines, pulmonary function testing.

Specific Aim #4- To evaluate and compare the effects on craving, reward and satisfaction when using the JUUL e-cigarette vs. tobacco cigarette.

Inclusion Criteria:

• Healthy on the basis of medical history and limited physical examination, as described below:
• - Heart rate < 105 beats per minute (bpm)
• - - Considered out of range if both machine and manual readings are above/below these thresholds.
• - Systolic Blood Pressure < 160 and > 90*
• - Diastolic Blood Pressure < 100 and > 50*
• Age: >= 21 & <=70 years old
• Body Mass Index (BMI) <= 38.0 (at PI's discretion for higher BMI if no other concurrent health issues)
• Willingness to avoid combusted marijuana up to 48 hours before each study visit
• Nicotine strength of e-liquid of usual e-cigarette > 0 mg/ml
• Group 1 Experienced E-cigarette users
• - Current use of tobacco cigarettes (<5 cigarettes per day)
• - Current e-cigarette use at least 15 days out of the past 30 days of a non-mod e-cigarette
• Group 2 Primary Tobacco cigarette users:
• - Currently smoking >= 5 cigarettes per day
• - Current e-cigarette use must be < 5 times per month
• Saliva cotinine >=50 ng/ml or urine cotinine and/or NicAlert=6
• Must have a smart phone, computer, or tablet and internet access (for remote procedures)

Exclusion Criteria:

• Medical
• - Heart disease
• - Seizures
• - Cancer
• - Thyroid disease (okay if controlled with medication)
• - Diabetes
• - Hepatitis B or C or Liver disease
• - Glaucoma
• - Kidney disease or urinary retention
• - History of stroke
• - An ulcer in the past year
• - Active use of an inhaler for Asthma or Chronic Obstructive Pulmonary Disease (COPD)
• Psychiatric conditions
• - Current or past schizophrenia, and/or current or past bipolar disorder
• - Major depression, current or within the past year
• - Major personality disorder
• - Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the principal investigator (PI) and/or medical monitor and considered for inclusion
• - History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's or medical monitor's approval
• Drug/Alcohol Dependence
• - Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program
• - Positive toxicology test for illicit drugs at the screening visit (Tetrahydrocannabinol (THC) & prescribed medications okay)
• - Opioid replacement therapy (including methadone, buprenorphine, or other)
• Psychiatric medications
• - Current regular use of any psychiatric medications is exclusionary, with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRI) and current evaluation by the PI and/or medical monitor that the participant is otherwise healthy, stable, and able to participate
• Medications
• - Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
• - Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs)
• - Concurrent use of nicotine-containing medications
• - Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
• Use of Other Tobacco Products (OTP)
• - Any of the following products in combination more than 15 times in the past month
• - - smokeless tobacco (snus, oral snuff, chewing tobacco)
• - - pipes
• - - cigars, cigarillos, little cigars
• - - blunts, spliffs
• - - hookah
• Other/Misc. Chronic Health Conditions
• Fainting (within the last 30 days)
• Other "life threatening illnesses" as per PI's or medical monitor's discretion
• Pregnancy
• - Pregnancy (self-reported and urine pregnancy test)
• - Breastfeeding (determined by self-report)
• Concurrent participation in another clinical trial (at PI's discretion)
• Inability to read and write in English
• Planning to quit smoking or vaping within the next 60 days
• Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks
• Diagnosis of pneumonia in the past 3 months
• Uncomfortable with blood draws
• Known allergy to propylene glycol or vegetable glycerin