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

Rationale: Δ⁹-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. Objectives: The 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. Meterials and methods: This 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. Results: Mean maximal concentrations (C _max) were 135.1, 202.9 and 231.0 μg/L for THC and 9.2, 16.4 and 15.8 μg/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 C _max was observed. Heart rate and 'high' feeling significantly increased with increasing THC dose. Conclusions: This study demonstrates that the known linear association between THC dose and THC serum concentration also applies for high THC doses. © 2008 Springer-Verlag.