Influence of ethanol on cannabinoid pharmacokinetic parameters in chronic users
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Cannabis is not only the most widely used illicit drug worldwide but is also regularly consumed along with ethanol. In previous studies, it was assumed that cannabis users develop cross-tolerance to ethanol effects. The present study was designed to compare the effects of ethanol in comparison to and in combination with a cannabis joint and investigate changes in pharmacokinetics. In this study, 19 heavy cannabis users participated and received three alcohol dosing conditions that were calculated to achieve steady blood alcohol concentrations (BAC) of about 0, 0.5 and 0.7 g/l during a 5-h time window. Subjects smoked a Δ9-tetrahydrocannabinol (THC) cigarette (400 μg/kg) 3 h post-onset of alcohol dosing. Blood samples were taken between 0 and 4 h after smoking. During the first hour, samples were collected every 15 min and every 30 min thereafter. Mean steady-state BACs reached 0, 0.36 and 0.5 g/l. The apparent elimination half-life of THC was slightly prolonged (1.59 vs. 1.93 h, p < 0.05) and the concentration 1 h after smoking was slightly lower (24 vs. 17 ng/ml, p < 0.05) with the higher ethanol dose. The prolonged THC elimination might be explained by a small ethanol-mediated change in distribution to and from deep compartments. Concentrations and pharmacokinetics of 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCA) were not significantly influenced by ethanol. However, THCA concentrations appeared lower in both ethanol conditions, which might also be attributable to changes in distribution. Though not significant in the present study, this might be relevant in the interpretation of cannabinoid concentrations in blood.
KeywordsForensics/toxicology Drug monitoring/drug screening Kinetics Cannabis Ethanol Interaction
This study was supported by a grant from the German Society “Bund gegen Alkohol und Drogen im Straßenverkehr e.V.”.
- 1.EMCDDA Annual Report 2009: the state of the drugs problem in Europe (2009) European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal. http://www.emcdda.europa.eu/situation/cannabis/3, accessed 24 Sep 2010
- 2.Office of Applied Studies, SAMHSA, RTI International (2009) Concurrent illicit drug and alcohol use. The NSDUH Report March 19, 2009Google Scholar
- 3.Koehm M, Kauert GF, Toennes SW (2010) Influence of ethanol on the pharmacokinetics of methylphenidate’s metabolites ritalinic acid and ethylphenidate. Arzneimittelforschung 60:238–244Google Scholar
- 6.Dean RA, Christian CD, Sample RH, Bosron WF (1991) Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. FASEB J 5:2735–2739Google Scholar
- 11.Lukas SE, Benedikt R, Mendelson JH, Kouri E, Sholar M, Amass L (1992) Marihuana attenuates the rise in plasma ethanol levels in human subjects. Neuropsychopharmacology 7:77–81Google Scholar
- 12.Benowitz NL, Jones RT (1977) Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol. Clin Pharmacol Ther 22:259–268Google Scholar
- 13.Ramaekers JG, Theunissen EL, Brouwer M de, Toennes SW, Moeller MR, Kauert G (2010) Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users. Psychopharmacology (Berl) (in press)Google Scholar
- 14.Ramaekers JG, Kauert G, van Ruitenbeek P, Theunissen EL, Schneider E, Moeller MR (2006) High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology 31:2296–2303Google Scholar
- 15.Toennes SW, Ramaekers JG, Theunissen EL, Moeller MR, Kauert GF (2008) Comparison of cannabinoid pharmacokinetic properties in occasional and heavy users smoking a marijuana or placebo joint. J Anal Toxicol 32:470–477Google Scholar
- 16.Kauert GF, Ramaekers JG, Schneider E, Moeller MR, Toennes SW (2007) Pharmacokinetic properties of delta9-tetrahydrocannabinol in serum and oral fluid. J Anal Toxicol 31:288–293Google Scholar
- 19.Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Herning RI, Cadet JL, Huestis MA (2009) Implications of plasma delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers. J Anal Toxicol 33:469–477Google Scholar