Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana

Abstract

delta 9-Tetrahydrocannabinol (THC), the primary psychoactive constituent of marijuana, is rapidly transferred from lungs to blood during smoking. Oxidative metabolism of THC yields the active metabolite, 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC), and the inactive metabolite, 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Characterization of THC's absorption phase is important because of the rapidity with which THC penetrates the central nervous system to produce psychoactive effects. This study incorporated a highly automated procedure to sample blood and to capture rapid drug level changes during and following smoking. Human subjects smoked one marijuana cigarette (placebo, 1.75%, or 3.55% THC) once a week according to a randomized, crossover, double-blind Latin square design. Samples were analyzed by GC/MS for THC, 11-OH THC, and THCCOOH. THC levels increased rapidly, peaked prior to the end of smoking, and quickly dissipated. Mean peak 11-OH-THC levels were substantially lower than THC levels and occurred immediately after the end of smoking. THCCOOH levels increased slowly and plateaued for an extended period. The mean peak time for THCCOOH was 113 min and a correspondingly longer time course of detection was observed. This study provides the first complete pharmacokinetic profile of the absorption of THC and appearance of metabolites during marijuana smoking. These findings have implications for understanding the mechanisms underlying the performance-impairing effects of marijuana, as well as for aiding forensic interpretation of cannabinoid blood levels.