Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH
Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH
This study will examine the short-term cardiovascular (CV) effects of e-liquid pH in a
 randomized, crossover clinical and behavioral pharmacology study of experienced adult
 e-cigarette users (N=21). The specific aim of the study is to assess the impact of changes in
 e-liquid pH on nicotine pharmacokinetics, cardiovascular, and subjective effects of
 e-cigarettes.
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-liquid pH.
 Three e-liquid pH conditions will be assessed on all participants: 5, 7, and 9.

 Hypothesis 2a: The rate of systemic nicotine absorption is inversely related to e-liquid pH
 and results in lower peak blood nicotine levels at higher pH.

 Hypothesis 2b: Heart rate acceleration will decrease and subjective measures of sensation in
 the throat, reward, and satisfaction will increase with increasing e-liquid pH.
Inclusion Criteria:

 -  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

 -  Use e-cigarettes on at least 15 days in the past 30 for at least 3 months

 -  Smoke 10 or fewer cigarettes/tobacco products per day in the last 30 days

 -  Willing to use mod e-cigarette

 -  Willing to abstain from tobacco product use for night before study

 -  Age: > 21 years old and < 70 years old

 -  Using e-liquid > 0mg/ml nicotine

 -  Saliva cotinine of ≥ 30 ng/ml or NicAlert=6 (in cases where lab turn around time will
 delay study procedure)

 Exclusion Criteria:

 -  Seizures

 -  Cancer

 -  Hepatitis B or C or Liver Disease

 -  Oral Thrush

 -  Heart disease

 -  Glaucoma

 -  Kidney disease or urinary retention

 -  Diabetes

 -  High Blood Pressure (taking sympatholytic medications such as alpha and beta blockers)

 -  History of stroke

 -  An ulcer in the past year

 -  Thyroid disease (okay if controlled with medication)

 -  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 study physician and considered for inclusion.

 -  History of psychiatric hospitalizations are not exclusionary, but study participation
 will be determined as per study physician's approval

 -  Recent onset or change in cough, fever and/or abdominal symptoms (vomiting or pain) in
 the past two weeks. (If yes, participant can re-screen when symptoms resolve).

 -  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 (including methadone, buprenorphine, or other)

 -  Positive urine cannabis is not exclusionary but participant must report use of
 cannabis and agree to abstain from cannabis use for the duration of the study

 -  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 CYP2A4 (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 sympatholytic medications that affect cardiovascular conditions including
 hypertension, (Example: beta and alpha-blockers)

 -  Other/Misc. Chronic Health Conditions

 -  Fainting (within the last 30 days)

 -  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 vaping within the next 60 days

 -  Uncomfortable with getting blood drawn