Short communicationExercise increases plasma THC concentrations in regular cannabis users
Introduction
Cannabis is the most widely used illicit drug in the world and its use can promote cognitive and psychomotor impairment (Degenhardt and Hall, 2012, Ramaekers et al., 2011). Testing for cannabinoids is increasingly being performed at the roadside and in the workplace, with many countries implementing “zero tolerance” or per se limits on blood cannabinoid concentrations for driving, analogous to those imposed with alcohol (Bergamaschi et al., 2013, Vindenes et al., 2012). A cannabinoid positive test can have major repercussions for individuals through sanctions imposed by the criminal justice system or employers. This is despite considerable uncertainty as to whether a positive test necessarily indicates psychomotor impairment or recent cannabis use (Karschner et al., 2009b, Ramaekers et al., 2011).
The main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC), is highly lipophilic, and accumulates in adipose tissue where it may remain for long durations (Kreuz and Axelrod, 1973). THC has been detected in human fat biopsies 28 days following exposure to cannabis (Johansson et al., 1989) and inpatient detoxification studies typically detect cannabinoids in heavy users after many days of abstinence (Karschner et al., 2009a, Karschner et al., 2009b). We have recently shown that fasting can increase blood cannabinoid concentrations in rats pre-treated with THC due to mobilization of THC from fat tissue undergoing metabolism (Gunasekaran et al., 2009). This suggests that blood cannabinoid concentrations in human cannabis users might be elevated under conditions of increased fat utilization, such as exercise, stress or fasting.
We examined here whether regular cannabis users subjected to fasting or exercise can display elevated plasma cannabinoids. We chose moderate intensity cycling as our exercise as it promotes lipolysis, particularly in fasted individuals (Achten and Jeukendrup, 2004). Cannabis users were subjected to moderate intensity exercise on a stationary bicycle either: (1) after a 12 h overnight fast, or (2) in a non-fasted condition. Plasma concentrations of THC and its metabolite THC-COOH were analyzed, as well as free fatty acids (FFA) and glycerol, two markers of lipolysis.
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Study population
A total of 15 regular cannabis users (recent cannabis use ≥5 days per week for ≥4 weeks) were recruited from the Sydney area through print media advertisements and subsequent telephone interview. Of these, 14 participants completed the experimental protocol over 2 days at The Langton Centre, an outpatient drug and alcohol clinic. The study was approved by the NSW Health Human Research Ethics Committee (Northern Sector).
The study design is shown in Fig. 1. Participants were allocated to either a
Effects of fasting
Neither the fasted group (n = 7) nor the non-fasted group showed significant change in plasma THC (Fig. 2A), THC-COOH (Fig. 2B) or in concentrations of glycerol (fasted baseline = 63.8 ± 11.6 μM to 55.7 ± 7.8 μM 24 h later; non-fasted baseline 57.8 ± 22.2 μM to 77.1 ± 12.8 μM 24 h later (all data mean ± SEM)). However relative to their own baseline on Day 1 the fasted group, but not the non-fasted group, showed significantly elevated FFAs (t(6) = 2.96, p < 0.05) (Fig. 2C) and significantly decreased glucose levels (t
Discussion
Our research using rats demonstrated that blood THC and THC-COOH concentrations are increased under conditions of fat utilization, due to fat-sequestered THC being redistributed into the systemic circulation (Gunasekaran et al., 2009). Here we show for the first time that moderate exercise on a stationary bicycle induces lipolysis and increases plasma THC concentrations in regular cannabis users.
In contrast, fasting for at least 12 h did not significantly increase plasma THC, THC-COOH or
Role of funding source
This study was supported by funds from the National Cannabis Prevention and Information Centre (NCPIC) and from the National Health and Medical Research Council of Australia (Project # 556301).
Contributors
Prof. Iain S. McGregor, A/Prof. Nicholas Lintzeris, Dr. Kieron Rooney, Dr. Raimondo Bruno designed the study. Mr. Alexander Wong, A/Prof. Jonathon C. Arnold, Dr. Melissa Norberg and Dr. Mark E. Montebello wrote the study protocol. Mr. Alexander Wong managed participant recruitment. Mr. Alexander Wong, Dr. Melissa Norberg and Dr. Mark E. Montebello coordinated the study. Mr. Alexander Wong and Ms. Jessica Booth performed sample analyses. Mr. Alexander Wong, A/Prof. Jonathon C. Arnold and Prof.
Conflict of interest
The authors declare no conflicts of interest.
Acknowledgements
Alexander Wong was supported by a Postgraduate Scholarship in Analytical Toxicology/Pharmacology. We are grateful to Michael Bowen for statistical advice. We thank NCPIC and Jan Copeland for their enthusiastic support of this project.
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