Vaping THC From Electronic Cigarettes

Electronic cigarettes (e-cigarettes) have proliferated at a rapid rate since their
introduction into the US market in 2007, and their use as a form of nicotine delivery far
outpaced the science base (1, 2). Although the design of these devices continues to evolve,
we have previously described nicotine intake, systemic retention, pharmacokinetics, and
vaping behavior associated with self-administration of e-cigarettes (3, 4) . We demonstrated
that while the shape of the plasma nicotine concentration-time curve for e-cigarettes is
similar to tobacco cigarettes, the maximum plasma nicotine concentration is, on average,
lower for e-cigarettes. During ad libitum access, e-cigarettes were vaped intermittently in
groups of 2-5 puffs or single puffs such that plasma nicotine levels rose gradually and
peaked at the end of the 90-minute session. This differs from the rapid increase in plasma
nicotine observed during controlled use of e-cigarettes or during tobacco cigarette smoking.
Taken together, these results indicate that e-cigarettes have the potential to produce and
sustain nicotine addiction but their use and abuse liability may differ from tobacco
cigarettes.

The study is designed as a within-subjects, single-blinded crossover study. Fourteen smokers
of tobacco cigarettes and cannabis will switch between three conditions, namely: (a) vaping
cannabis leaf, (b) vaping tobacco containing nicotine and (c) vaping a combination of
cannabis leaf and tobacco containing nicotine. All participants will vape each product with
the PAX loose-leaf vaporizer, which will be purchased by the study team. The cannabis leaf
will be obtained through the National Institute on Drug Abuse Drug Supply Program. The
tobacco-containing nicotine, used in conditions (b) and (c) will come from commercially
available Marlboro brand cigarettes. The same amount of cannabis or tobacco will be used in
all conditions.

The study will be conducted during three outpatient visits separated by at least 48 hours.
The order of treatment (cannabis leaf, tobacco with nicotine, cannabis leaf & tobacco with
nicotine) will be counterbalanced between subjects. Subjects will be blinded to the content
of the vaporizer on the study day but will be told during screening that they will vape
cannabis alone, tobacco alone, and cannabis plus tobacco with nicotine.

While scientists struggle to keep up with the latest electronic cigarette trends, the use of
these devices for cannabis rather than nicotine is increasingly prevalent. electronic
cigarette use is not restricted to nicotine. Marijuana, the most widely used illicit drug (5)
has traditionally been combusted but the vaping of loose-leaf marijuana and THC oil has been
increasing (6). the latest national data show that 7.6% of current marijuana users (past 30
days) and 9.9% of ever cannabis users (lifetime) administered THC through a vaporizer or
electronic device (6) (the study did not differentiate between vaporizers and electronic
devices like e-cigarettes). The prevalence of vaped marijuana or THC is higher among younger
adults. Prevalence of vaped marijuana/THC among 18-24 and 25-34 year-old ever marijuana users
was 19.3% and 16.3%, respectively, compared to 8.8% for 35-49 year-olds and 5.7% for those 50
years and over (6). A recent study also showed high rates of cannabis vaping among high
school students (18.0% among ever e-cigarette users) (7). Smoking of a combination of tobacco
and marijuana in cigarette form is also common, particularly in Europe (8) (9). However, very
little is known about the safety and pharmacokinetics of this co-administration making it a
critical area of research.

Inclusion

- Age ≥21 years ≤ 70 years

- Regular user of tobacco cigarettes (daily or most days)

- Regular user of cannabis in any form (combusted or ingested) at least 5 days out of
the month.

- Positive for THC on screening toxicology test

- Willing to abstain from tobacco smoking and all other combustible products (ex:
cigars) for 12 hours prior to each outpatient hospital admission.

- Willing to abstain from smoking/ingesting cannabis for 12 hours prior to each
outpatient hospital admission.

- Willing to abstain from using any kind of nicotine products for 12 hours prior to each
outpatient hospital admission (ex: electronic cigarettes, nicotine replacement
therapy).

- Saliva cotinine ≥ 30 ng/mL and/or NicAlert of 6

- Healthy (based on limited physical examination and medical history collected during
screening)

- Heart rate < 105 BPM

- Systolic Blood Pressure < 160 and > 90 [considered out of range if both machine and
manual readings are above/below these thresholds]

- Diastolic Blood Pressure < 100 and > 50 [considered out of range if both machine and
manual readings are above/below these thresholds]

- Body Mass Index ≤ 38.0

Exclusion

- Medical (The following unstable medical conditions):

- Heart disease

- Uncontrolled hypertension

- Thyroid disease (okay if controlled with medication)

- Diabetes

- Hepatitis B or C or Liver disease

- Glaucoma

- Prostatic hypertrophy

- History of paranoia after marijuana use

- Psychiatric conditions

- Current or past schizophrenia, and/or current or past bipolar disorder

- Adult onset ADHD (if being treated)

- Participants with current or past 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

- 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 and are currently
abstaining from drug and alcohol

- Positive toxicology test at the screening visit (THC & prescribed medications okay)

- Methadone replacement therapy

- Scoring a 2 or higher on the Severity of Dependence Scale for cannabis use.

- Psychiatric medications

- Current regular use of any 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.

- Other Medications

- Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example:
rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).

- Concurrent use of nicotine-containing medications

- Other/Misc. Chronic Health Conditions

- Oral thrush

- Fainting

- Untreated thyroid disease

- Other "life threatening illnesses" as per study physician's discretion

- Use of Other Tobacco Products (OTP); any of the following products in combination more
than 15 times in the past month

- smokeless tobacco

- pipes

- cigars, cigarillos

- blunts, spliffs

- 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 smoking or cannabis use within the next 60 days