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 is to determine the impact of e-cigarette pH levels 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-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

De-identified data may be shared with research collaborators during the course of the study.