• Psychopharmacology · Dec 2008

    Randomized Controlled Trial

    Delta-9-tetrahydrocannabinol (THC) serum concentrations and pharmacological effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg THC.

    • Claudine C Hunault, Tjeert T Mensinga, Irma de Vries, Hermien H Kelholt-Dijkman, Jani Hoek, Maaike Kruidenier, Marianne E C Leenders, and Jan Meulenbelt.
    • National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands. claudine.hunault@rivm.nl
    • Psychopharmacology (Berl.). 2008 Dec 1; 201 (2): 171-81.

    RationaleDelta9-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). The pharmacokinetics of THC after smoking cannabis cigarettes containing more than approximately 35 mg THC (3.55% THC cigarettes) is unknown. To be able to perform suitable exposure risk analysis, it is important to know if there is a linear relation at higher doses.ObjectivesThe present study aimed to characterise the pharmacokinetics of THC, the active metabolite 11-OH-THC and the inactive metabolite THC-COOH after smoking a combination of tobacco and cannabis containing high THC doses.Materials And MethodsThis double-blind, placebo-controlled, four-way, cross-over study included 24 male non-daily cannabis users (two to nine joints per month). Participants were randomly assigned to smoke cannabis cigarettes containing 29.3, 49.1 and 69.4 mg THC and a placebo. Serial serum samples collected over a period of 0-8 h were analysed by liquid chromatography electrospray tandem mass spectrometry. Effects on heart rate, blood pressure and 'high' feeling were also measured.ResultsMean maximal concentrations (Cmax) were 135.1, 202.9 and 231.0 microg/L for THC and 9.2, 16.4 and 15.8 microg/L for 11-OH-THC after smoking a 29.3-, 49.1- and 69.4-mg THC cigarette, respectively. A large inter-individual variability in Cmax was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose.ConclusionsThis study demonstrates that the known linear association between THC dose and THC serum concentration also applies for high THC doses.

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