Cigarette Harm Reduction With Electronic Cigarette Use

Daily cigarette smokers who are familiar with e-cigarette (EC) use will be instructed to use
only NIDA Standardized Research Electronic Cigarettes (SREC) and tobacco cigarettes (TC)
while enrolled on the study. Our overall goals are two-fold: (1) to compare nicotine and
toxicant exposure and pharmacological effects of SREC used alone vs tobacco cigarettes alone
(TC), or dual use; and (2) using SREC alone, TC alone, or ad libitum SREC use combined with
50% reduction in usual TC use as a model for dual use, to examine the extent to which
nicotine and toxicant exposure and biomarkers of potential harm compare among the 3 groups.
The former would inform the effects of total switching, the latter would inform the potential
harm reducing effects of smoking fewer TC while using EC.

Inclusion Criteria:

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

Heart rate < 105 BPM Systolic Blood Pressure < 160 and >90 Diastolic Blood Pressure < 100
and > 50 Body Mass Index ≤ 38.0 Expired CO ≥ 5ppm Current regular "dual" user of both EC
and TC EC device use at least 10 or more days in the past 30 days Daily use of conventional
TC (at least 10 CPD, as confirmed by saliva cotinine >50 ng/ml and/or NicAlert=6) Age: ≥ 21
years old to ≤ 70 years old Willingness to use a non-menthol e-cigarette only (until
menthol flavored SREC becomes available) Willingness to abstain from marijuana for the
duration of the study

Exclusion Criteria:

Unstable medical conditions (such as unstable heart disease, seizures, cancer, uncontrolled
thyroid disease, diabetes, Hepatitis B or C or renal or liver impairment, glaucoma, history
of stroke, an ulcer in the past year, or active use of an inhaler for Asthma or COPD).

Psychiatric conditions (such as current or past schizophrenia and/or current or past
bipolar disorder, major personality disorder, or major depression current or within the
past year. Participants with current or past minor to moderate 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.

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.

Pregnancy or breastfeeding (by history and pregnancy test); women of childbearing potential
must be using an acceptable method of contraception

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 15 times in combination in the past month and must agree to abstain from
their use during the period of the study.]

Concurrent use of nicotine-containing medications

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 ok). Must not be on opioid replacement therapy.

Medications: Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6
(Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs). Use of
medications for cardiovascular conditions including hypertension (Example: beta and
alphablocking drugs). Use of stimulants (Example: Adderall)

Other/Misc Health Conditions: Oral thrush; fainting within the last 30 days; untreated
thyroid disease; other "life threatening illnesses" as per study physician's discretion.

Concurrent participation in another clinical trial Inability to read and write in English
Planning to quit smoking or vaping within the next 60 days A known propylene
glycol/vegetable glycerin allergy