Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power

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, 35, and 70 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 BPM*

- Systolic Blood Pressure < 160 and > 90*

- Diastolic Blood Pressure < 100 and > 50*

- Body Mass Index ≤ 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 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 SSRIs and
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