Please see NCT04053868 for the current version of this study

This study will examine the effects of electronic cigarette e-liquid nicotine content in a randomized, crossover clinical and behavioral pharmacology study of experienced adult e-cigarette users (N=36). The specific aim is to determine the impact of nicotine content of e-liquid on nicotine pharmacology, systemic exposure to toxic volatile organic compounds, and short-term cardiovascular effects.

This is a within-subjects, crossover design of advanced electronic cigarette users in which we will examine nicotine pharmacokinetics, subjective effects, daily nicotine intake and nicotine titration, short-term cardiovascular effects, and toxicant exposure when participants are using low vs. high nicotine e-liquids.

Hypothesis 1: E-cigarette users will titrate their intake of nicotine such that they will inhale fewer aerosol toxicants and suffer less harm to health when using higher vs. lower nicotine content e-liquids.

Hypothesis 2: Compared to low nicotine, high nicotine e-liquid use will have similar cardiovascular effects throughout the day (due to compensatory behavioral changes), with similar effects on heart rate, blood pressure, and catecholamine release.

Hypothesis 3: Exposure to volatile organic compounds (VOCs) will be lower when vaping high nicotine e-liquids compared to low nicotine e-liquids.

Inclusion Criteria:

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

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

• Systolic Blood Pressure < 160 and > 90*

• Diastolic Blood Pressure < 100 and > 50*

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

• Age: >= 21 years

• Age: <= 70 years

• Current regular user of open tank electronic cigarette (EC) (at least 20 times in the past 30 days) with e-liquid nicotine of 3-6 mg/mL.

• Non-smoker or non-daily cigarette smokers agreeing to abstain from cigarettes for the duration of the study.

• Saliva cotinine >50 ng/mL and/or NicAlert=6

• Carbon monoxide >= 5 ppm or per discretion of Principal Investigator

Exclusion Criteria:

• Medical
• Heart disease
• Seizures
• Cancer
• Thyroid disease (okay if controlled with medication)
• Diabetes
• Hepatitis B or C or Liver disease
• Glaucoma
• Kidney disease or urinary retention
• History of stroke
• An ulcer in the past year
• 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 PI and considered for inclusion
• History of psychiatric hospitalizations is not exclusionary, but study participation will be determined as per PI'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 for illicit drugs at the screening visit (THC & prescribed medications okay)
• Opioid replacement therapy (including methadone, buprenorphine, or other)
• Psychiatric medications
• Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRIs) and serotonin-norepinephrine reuptake Inhibitors (SNRIs) and current evaluation by the PI 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, carbamazepine, phenobarbital, and other anticonvulsant drugs).
• Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
• Concurrent use of nicotine-containing medications
• Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
• Other/Misc. Chronic Health Conditions
• Oral thrush
• Fainting (within the last 30 days)
• Other "life threatening illnesses" as per PI's discretion
• Pregnancy
• Pregnancy (self-reported and urine pregnancy test)
• Breastfeeding (determined by self-report)
• Concurrent participation in another clinical trial
• Inability to read and write in English
• Planning to quit vaping within the next 60 days
• Concurrent regular use of marijuana (occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study)
• Use of other tobacco products, smokeless tobacco, pipes, cigars/cigarillos, blunts/spliffs (no more than 10 times in the past month and must agree to abstain from their use during the period of the study)