Primary Outcome Measures:

  • Amount of THC inhaled and systematically retained [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    change in e-cigarette weight × concentration of THC or nicotine in e-liquid

  • Max plasma THC concentration (Cmax) [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Blood THC concentrations

  • Time to max plasma concentration (Tmax) [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Blood THC concentrations

  • Area under the curve (AUC) [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Blood THC concentrations

  • Heart rate [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    blood pressure/heart rate monitor

  • Liking [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Drug Effect Questionnaire (DEQ-5)

  • Craving [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Marijuana Craving Questionnaire—Short Form (MCQ-SF)

  • Reward [ Time Frame: Study Day 1-2 ] [ Designated as safety issue: No ]

    Minnesota Behavioral Scale or (Minnesota Nicotine Withdrawal Scale (MNWS)

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). Important questions revolved around their abuse liability and safety. Although the design of these devices continues to evolve, the investigators have previously described nicotine intake, systemic retention, pharmacokinetics, and effects, as well as vaping behavior and self-administration of e-cigarettes (3, 4). The investigators showed that e-cigarettes deliver as much nicotine from 15 puffs as a typical tobacco cigarette (~1 mg), most of which is systemically retained, and the shape of the plasma nicotine concentration-time curve is also similar to tobacco cigarettes, except that 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 cigarette.

Marijuana is the most widely used illicit drug (5). While marijuana has traditionally been combusted, vaping of either loose leaf marijuana or other forms of tetrahydrocannabinol (THC) extracts has been increasing (6). The latest national data show that 7.6% of current marijuana users (past 30 days) and 9.9% of ever marijuana 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 using e-cigarettes among high school students (18.0% among ever e-cigarette users) (7).

Although e-cigarettes were not designed for use with THC extracts, which are more viscous than nicotine e-liquids, there is an abundance of YouTube videos demonstrating how to modify nicotine e-cigarettes for use with THC extracts as well as how to prepare THC e-liquids. There are also prepackaged cartridges with THC extracts that are compatible with e-cigarette batteries. Yet again, the science base has not kept up with the growing use of these products. The investigators currently have no data on THC delivery, pharmacokinetics, and effects of THC vaping with currently marketed e-cigarettes. Further, just as tobacco is mixed with marijuana for nicotinic reinforcement of THC in products such as blunts (8), it is not inconceivable that THC may also be mixed with nicotine e-liquids when diluting THC extracts. Therefore, it is important to understand the pharmacology and safety of simultaneous intake of nicotine and THC from vaping.

The study is designed as a within-subjects pharmacokinetic comparison. Fourteen (14) e-cigarette users who are also current marijuana/THC users will switch between two THC e-liquid conditions, namely, (a) e-liquid solution containing 40% THC and no nicotine, and (b) e-liquid solution containing 40% THC and 0.6% (6 mg/mL) nicotine, during 2 outpatient visits. The outpatient days will comprise of a fixed-puffing regimen. Study days will be separated by at least 48 hours. The order of treatment (THC only and THC with nicotine) will be counterbalanced between subjects. Subjects will be blinded to the content of the e-cigarette (i.e. THC only vs THC + nicotine).