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.

Eligibility Criteria:
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