Clinical trial NCT02955329: Vaping THC From Electronic Cigarettes
Official title: Vaping THC From Electronic Cigarettes: a Novel Evaluation of Intake and Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Marijuana Dependence
Keywords: THC
Tobacco
Vaping
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2016-11-04
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This study aims to understand THC pharmacology and the safety of cannabis vaping, including the pharmacology and safety of co-administration of nicotine and THC. 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. 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.

Detailed description: 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. 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. 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 has traditionally been combusted but the vaping of loose-leaf marijuana and THC oil has been increasing. 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 (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. A recent study also showed high rates of cannabis vaping among high school students (18.0% among ever e-cigarette users). Smoking of a combination of tobacco and marijuana in cigarette form is also common, particularly in Europe. However, very little is known about the safety and pharmacokinetics of this co-administration making it a critical area of research.

Eligibility criteria: 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 Tetrahydrocannabinol (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 beats per minute (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 Attention-deficit/hyperactivity disorder (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 Selective Serotonin Reuptake Inhibitors (SSRIs) and serotonin-norepinephrine reuptake Inhibitors (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

Primary outcomes:
measure: Mean Delivered and Retained Doses
timeFrame: Study Day 1-3
measure: Median Peak THC Concentration (Cmax)
timeFrame: Study Day 1-3
measure: Median Peak Nicotine Concentration (Cmax)
timeFrame: Study Day 1-3
measure: Median THC Exposure
timeFrame: Study Day 1-3
measure: Median Nicotine Exposure
timeFrame: Study Day 1-3
measure: Mean Heart Rate
timeFrame: Study Day 1-3
measure: Mean Score on the Drug Effects Questionnaire (DEQ)
timeFrame: Study Day 1-3
measure: Mean Scores on the Marijuana Craving Questionnaire-Short Form (MCQ-SF)
timeFrame: Study Day 1-3
measure: Mean Scores on the Modified Cigarette Evaluation Questionnaire (mCEQ)
timeFrame: Study Day 1-3
measure: Mean Scores on the Positive Affect Negative Affect Schedule (PANAS)
timeFrame: Study Day 1-3
measure: Mean Scores on the Minnesota Nicotine Withdrawal Scale (MNWS)
timeFrame: Study Day 1-3
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: King BA, Patel R, Nguyen KH, Dube SR. Trends in awareness and use of electronic cigarettes among US adults, 2010-2013. Nicotine Tob Res. 2015 Feb;17(2):219-27. doi: 10.1093/ntr/ntu191. Epub 2014 Sep 19.
citation: Arrazola RA, Singh T, Corey CG, Husten CG, Neff LJ, Apelberg BJ, Bunnell RE, Choiniere CJ, King BA, Cox S, McAfee T, Caraballo RS; Centers for Disease Control and Prevention (CDC). Tobacco use among middle and high school students - United States, 2011-2014. MMWR Morb Mortal Wkly Rep. 2015 Apr 17;64(14):381-5.
citation: St Helen G, Havel C, Dempsey DA, Jacob P 3rd, Benowitz NL. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016 Mar;111(3):535-44. doi: 10.1111/add.13183. Epub 2015 Nov 11.
citation: St Helen G, Ross KC, Dempsey DA, Havel CM, Jacob P 3rd, Benowitz NL. Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access. Tob Regul Sci. 2016 Oct;2(4):363-376. doi: 10.18001/TRS.2.4.8.
citation: Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. NSDUH; 2015.
citation: Schauer GL, King BA, Bunnell RE, Promoff G, McAfee TA. Toking, Vaping, and Eating for Health or Fun: Marijuana Use Patterns in Adults, U.S., 2014. Am J Prev Med. 2016 Jan;50(1):1-8. doi: 10.1016/j.amepre.2015.05.027. Epub 2015 Aug 12.
citation: Morean ME, Kong G, Camenga DR, Cavallo DA, Krishnan-Sarin S. High School Students' Use of Electronic Cigarettes to Vaporize Cannabis. Pediatrics. 2015 Oct;136(4):611-6. doi: 10.1542/peds.2015-1727. Epub 2015 Sep 7.
citation: Akre C, Michaud PA, Berchtold A, Suris JC. Cannabis and tobacco use: where are the boundaries? A qualitative study on cannabis consumption modes among adolescents. Health Educ Res. 2010 Feb;25(1):74-82. doi: 10.1093/her/cyp027. Epub 2009 Jun 10.
citation: Amos A, Wiltshire S, Bostock Y, Haw S, McNeill A. 'You can't go without a fag...you need it for your hash'--a qualitative exploration of smoking, cannabis and young people. Addiction. 2004 Jan;99(1):77-81. doi: 10.1111/j.1360-0443.2004.00531.x.