THC, or tetrahydrocannabinol, is the main psychoactive component of marijuana. After oral consumption, it is transferred to the liver, where it is metabolized by enzymes known as CYP2C and CYP3A. These enzymes convert THC to 11-OH-THC, which is also psychoactive, and then to 11-COOH-THC, which is not psychoactive. The half-life of marijuana is the time it takes for half of the drug to be metabolized and eliminated from the bloodstream. Most drug tests seek out THC, and other cannabinoids like cannabidiol (CBD) are substrates for CYP3A4 and CYP2C19. Inhibitors like ketoconazole can increase the plasma concentration of CBD by approximately twofold, while inducers like rifampicin can reduce CBD levels by 50 to 60%.
Omeprazole, a modest CYP2C19 inhibitor, does not alter the plasma concentration of CBD. The metabolites of THC are usually stored in fat cells, so the higher your body fat or BMI, the slower you can metabolize and excrete marijuana. Ketoconazole has been reported to increase the maximum concentration and area under the concentration-time curve of THC by 1.2 and 1.8 times respectively. The bioavailability of 9-THC varies depending on the depth of inhalation, duration of inhalation and retention of respiration. The evidence of numerous diffuse in vivo effects supports the hypothesis of a non-specific interaction of THC. Some people will try to exercise before a drug test in order to reduce the percentage of THC found in urine by diluting it, but this will not completely eliminate its metabolites. The hydroxylation of 9-THC generates the psychoactive compound 11-hydroxy 9_Tetra hydrocannabinol (11-OH-THC) and subsequent oxidation generates the inactive 11-nor-9-carboxy-9-tetrahydrocannbinol (THCCOOH).
Upon assimilation through the blood, 9-THC rapidly penetrates fatty tissues and highly vascularized tissues, including the brain and muscles. Most methods used to reduce THC levels must be used for an extended period, during which the body will naturally shed THC anyway. People can experience THC toxicity when they consume high doses of marijuana, especially in edibles form. The objective of this review is to analyze the properties of cannabinoids, mainly 9_THC and its metabolites, and their clinical implications.
