This study will examine the short-term cardiovascular (CV) effects of e-cigarette device power in a randomized, crossover clinical and behavioral pharmacology study of experienced adult e-cigarette users (N=21). The specific aim is to determine the impact of e-cigarette power on nicotine pharmacology, systemic exposure to toxic volatile organic compounds (VOCs), and short-term cardiovascular effects.

This is a single-site, randomized, crossover study of experienced adult e-cigarette users to assess nicotine exposure, toxicant exposure, and the short-term CV effects of e-cigarette power. Three power levels will be assessed on all participants: 10, 15, and 20 watts.

Hypothesis 1a: Systemic nicotine exposure and subjective measures of sensation in the throat, reward, and satisfaction will increase with increasing power in the e-cigarette device.

Hypothesis 1b: Mercapturic acid metabolites of volatile organic compounds (VOCs), particularly acrolein, will increase with e-cigarette power.

Hypothesis 1c: CV effects increase with higher power, and are manifested as changes in hemodynamic parameters, hormonal release, and biomarkers of endothelial function, platelet activation, inflammation, and oxidative stress.

Inclusion Criteria:

• Use e-cigarettes on at least 25 days in the past 30 for at least 3 months and have not used another tobacco product in the past 30 days

• Healthy on the basis of medical history and limited physical examination (screening visit), as described below:

• Heart rate < 105 beats per minute (BPM)*

• Systolic Blood Pressure < 160 and > 90*

• Diastolic Blood Pressure < 100 and > 50*

• Body Mass Index (BMI) ≤ 38.0 (at investigator's discretion for higher BMI if no other concurrent health issues)

  *Considered out of range if both machine and manual readings are above/below these thresholds.

• Any race/ethnicity

Exclusion Criteria:

• Used tobacco products other than e-cigarettes in past 30 days
• Expired carbon monoxide of over 5 ppm at screening
• The following unstable medical conditions:
• Heart disease
• Uncontrolled hypertension
• Thyroid disease (not hypo or hyper, controlled with medication)
• Diabetes
• Hepatitis B or C or Liver disease
• Glaucoma
• Prostatic hypertrophy
• Psychiatric conditions:
• Current or past schizophrenia, and/or current or past bipolar disorder
• Adult onset attention deficit hyperactivity disorder (ADHD) (if being treated)
• Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion
• Psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician'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 at the screening visit (THC & prescribed medications okay)
• Opioid replacement therapy
• Positive urine cannabis is not exclusionary but participant must report use of cannabis in any form on not more than 2 times per week to be eligible
• Psychiatric medications:
• Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRIs) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate.
• Medications
• Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).
• Concurrent use of nicotine-containing medications
• Other/Misc. Chronic Health Conditions
• Oral thrush
• Fainting
• Untreated thyroid disease
• Other "life threatening illnesses" as per study physician's discretion
• Pregnancy
• Pregnancy (self-reported and urine pregnancy test)
• Breastfeeding (determined by self-report)
• Concurrent participation in another clinical trial
• Inability to communicate in English
• Planning to quit smoking or vaping within the next 60 days