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Tuesday, August 26 Metabolism and Disposition of Drugs

Cone E.J.
National Institute on Drug Abuse, NIH, Addiction Research Center, Division of Intramural Research, PO Box 5180, Baltimore, MD 21224, USA

Marijuana smoking delivers D9-tetrahydrocannabinol (THC) to the lungs where absorption into the bloodstream is rapid, followed by delivery to the brain. The efficiency of the smoking process is dependent upon multiple factors including cigarette potency, depth and length of inhalation and experience of the smoker. Inter-subject variability of kinetic parameters, e.g., peak THC concentrations, is known to vary widely; however, little is known regarding the stability of kinetic parameters within the same subject. A study was designed to evaluate the effects of marijuana in which subjects smoked single cigarettes of the same potency (3.55% THC) on multiple occasions (3, 4 or 5 repetitions) separated by 1-week.

Six healthy male subjects with recent histories of marijuana smoking provided informed consent. Subjects smoked the cigarettes in 8-scheduled puffs. Blood samples were collected before and periodically after smoking and were analyzed by gas chromatography-mass spectrometry for THC. Average Cmax (observed) between subjects range from 78.0 ng/mL to 153.8 ng/mL with an overall mean of 122.6 ng/mL; within subjects coefficients of variation (CVs) ranged from and 5.7% to 37.6% (ave = 17.6%) and between subjects' CV was 23.5%. The greatest variation in individual THC Cmax (observed) concentrations was from 61.0 ng/mL to 130.0 ng/mL between equivalent smoked doses. Blood data were fitted by WinNonlin (Scientific Consulting) to a 2-compartment model. Average elimination half-lives (beta phase) between subjects ranged from 36.8 min to 62.8 min; within subject CVs varied from 9.0% to 28.6% (ave = 21.2%) and between subjects' CV was 21.8%. Overall, most subjects demonstrated moderate consistency in kinetic parameters, but one subject's AUC and Cmax varied by approximately 100% during repeated dosing. These data indicated that despite stringent control over dose and smoking parameters, substantial variability is introduced by individual subjects in the amount of THC delivered to the bloodstream during marijuana smoking.

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