Elsevier

Drug and Alcohol Dependence

Volume 175, 1 June 2017, Pages 67-76
Drug and Alcohol Dependence

Full length article
Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration

https://doi.org/10.1016/j.drugalcdep.2017.02.003Get rights and content

Highlights

  • Subjective effects were similar after smoked and vaporized cannabis.

  • Oral cannabis significantly increased subjective ratings in occasional smokers only.

  • Frequent smokers showed partial tolerance to subjective effects after oral dosing.

  • Maximum heart rate increases were not significantly different between active routes.

  • Smoking significantly increased CO exposure compared to vaporization.

Abstract

Background

Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis’ subjective and physiological effects following multiple administration routes.

Methods

Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ9-tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54 mg).

Results

Participants’ subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers’ ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers’ maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers’ maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5 h after smoking (mean 12.2 bpm) and vaporization (10.7 bpm), and at 1.5 h (13.0 bpm) and 3 h (10.2 bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25–6 h post-dose compared to vaporization.

Conclusions

All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers’ maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments.

Introduction

While smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. In a survey of U.S. adults aged ≥18 years who had ever consumed cannabis, 29.8% reported consuming cannabis via “edibles or drinks”, and 9.9% by “vaporizer or other electronic device” (Schauer et al., 2016). Additionally, 22.4% and 18.8% reported ever utilizing 2 and ≥3 ways to administer cannabis, respectively, indicating the importance of characterizing cannabis’ effects after multiple administration routes.

Desired subjective effects are achieved after consumption of cannabis-containing foodstuffs. After five experienced cannabis smokers (all with 10 years use history) ingested brownies containing the equivalent of zero, one (∼22.4 mg THC), and two (∼44.8 mg THC) 2.8% THC cigarettes, significantly greater ratings on Feel Drug and Liking scales after the two-cigarette dose were observed compared to the one-cigarette dose (Cone et al., 1988); onset of effects was slow and variable, with peak responses occurring 2.5–3.5 post-dose.

Comparisons of subjective and physiological effects following smoked and oral cannabis were previously conducted. Following THC administrations via intravenous (5 mg THC injected over 2 min), smoked (19 mg THC), and oral (20 mg THC) routes, similar ratings of “high” were observed following all administrations, despite lower plasma THC concentrations after oral dosing, in participants with varied cannabis use histories (Ohlsson et al., 1980). In another investigation, active smoked (18.4–32.4 mg THC) cannabis or oral encapsulated (2.5–10 mg) THC produced significant increases in overall drug effect, peak high, and drug liking compared to placebo in participants that self-administered cannabis 1–3x/week (Chait and Zacny, 1992); ratings between smoked and oral routes were similar, but were not directly compared. Smoked and oral cannabis each significantly increased heart rate compared to placebo, with mean increases 18 and 8–9 bpm, respectively, relative to placebo (Chait and Zacny, 1992). Similarly, active oral and smoked cannabis (8.4–16.9 mg THC for both) produced significant increases in ratings for drug “feel”, “high”, and “want” compared to placebos, but effects following smoking were larger in participants that administered cannabis or hashish at least once in the prior 2 months (Wachtel et al., 2002); however, as with the previous study, ratings after oral and smoked routes were not directly compared. Another study administered either oral (20 mg THC 4x/daily) or smoked THC (3.1% THC, cigarette weights not provided) four times daily for 3 consecutive days to participants that averaged smoking 6.3 ± 5.6 cannabis cigarettes/day and ratings for “high”, “mellow”, and “good drug effect” following smoking were significantly greater than after oral administration (Hart et al., 2002); the authors concluded, though, that although subjective effects were slightly more pronounced after smoking for some measures, smoked and oral routes produced similar effects.

Smoked cannabis exposes users to harmful combustion by-products, including carbon monoxide (CO) (Hazekamp et al., 2006). CO is not released during edible consumption. However, the low bioavailability and slow, erratic absorption produced by oral cannabis (Ohlsson et al., 1980) suggests an alternative administration route could be useful for medicinal purposes. One such alternate route is vaporization. In a pilot study comparing smoked and vaporized cannabis in participants that smoked 3–10 cannabis cigarettes in the prior 30 days, plasma THC area under the curve (AUC) up to 6 h post-dose and ratings of “high” were not significantly different between smoking and vaporization at any dose, while exhaled CO concentrations were significantly greater following smoking at all cannabis potencies (Abrams et al., 2007).

The effectiveness of vaporized low (2.9% THC) and high (6.7% THC) cannabis doses in producing increased subjective ratings was demonstrated in occasional-to-moderate cannabis smokers (Hartman et al., 2016); blood THC concentrations were significantly associated with participants’ ratings of “anxious”, “good drug effect”, “high”, “restless”, “stimulated”, and “stoned”, with subjective effects persisting for 3.3–4.3 h post-dose. We also previously characterized cannabinoid blood pharmacokinetics following smoked, vaporized, and oral cannabis administrations (Newmeyer et al., 2016); frequent smokers’ maximum THC concentrations (Cmax) were significantly greater after smoking compared to vaporization, whereas occasional smokers’ THC Cmax were not different between the inhaled routes. In all participants, inhaled cannabis produced significantly greater THC Cmax than oral cannabis. Additionally, frequent smokers’ observed and baseline-adjusted THC Cmax after smoking and vaporization were significantly greater than THC Cmax in occasional smokers.

There are few studies directly comparing subjective and physiological effects, and expired CO concentrations following multiple cannabis administration routes, and none investigated differences between frequent and occasional cannabis smokers. We present a novel, placebo-controlled investigation in which subjective and objective effects were evaluated following controlled smoked, vaporized, and oral cannabis administrations to frequent and occasional cannabis smokers with a within-subject study design.

Section snippets

Participants

Adults 18–50 years old provided written, informed consent to participate in this National Institute on Drug Abuse (NIDA) Institutional Review Board-, Food and Drug Administration-, and Drug Enforcement Administration-approved study (Newmeyer et al., 2016, Swortwood et al., 2016). Inclusion criteria were average self-reported cannabis intake frequency ≥2x/month but <3x/week (occasional smokers), or ≥5x/week (frequent smokers) for the previous three months, and a positive urine cannabinoid screen

Participants

Table 1 summarizes 11 frequent and 9 occasional cannabis smokers’ demographic information (ages 19–46 y, 75% male, 75% African American). Participant K was originally recruited as an occasional cannabis smoker, but reclassified as a frequent smoker because baseline and post-dose THC and metabolite concentrations were consistent with published frequent smoker data (Desrosiers et al., 2014, Schwope et al., 2011); all other participants’ cannabinoid pharmacokinetics were consistent with

Discussion

We sought to characterize and compare subjective and objective effects after smoked, vaporized, and oral cannabis in frequent and occasional cannabis smokers. Comparisons of subjective effects following controlled smoked and oral (Chait and Zacny, 1992, Hart et al., 2002, Ohlsson et al., 1980, Wachtel et al., 2002) or smoked and vaporized (Abrams et al., 2007) cannabis were previously performed. The only difference between smoking and vaporization observed here was in frequent smokers’ ratings

Conflict of interest

The authors declare that there are no conflicts of interest.

Role of funding source

This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. The funding source had no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Contributors

Dr. Huestis (principal investigator) was responsible for all aspects of the study and designed the protocol with Dr. Swortwood and Mr. Newmeyer. Dr. Swortwood and Mr. Newmeyer were responsible for data collection and review of study methods. Dr. Abulseoud was responsible for reviewing participant eligibility, and ensuring their safety during the study. Mr. Newmeyer was responsible for data analysis and drafting the manuscript. All authors contributed to and approved the final manuscript.

Acknowledgements

The authors would like to thank Dr. Sandrine Pirard for her contribution to study design, and the contributions of Ms. Megan Hall and the clinical staffs of the Intramural Research Program, National Institute on Drug Abuse, and the Clinical Research Unit, Johns Hopkins Bayview Medical Center. MNN acknowledges the Graduate Partnership Program, NIH.

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