Marijuana is the common name given to plants in the Cannabis genus. Plants in this genus are well known for their psychoactive properties. Delta-9-tetrahydrocannabinol, more commonly referred to as THC, is the principal psychoactive component of the Cannabis plant.
Metabolism
- Delta-9-tetrahydrocannabinol (THC) is metabolized mainly in the liver to the active metabolite11-hydroxy-tetrahydrocannabinol (THC-OH) by replacement of a methyl group (-CH3) with a hydroxyl group (-OH).
- THC-OH is oxidized to 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) by replacing the hydroxyl group (-OH) with a carboxyl group (-COOH).
- More than 100 metabolites have been identified in humans and animals, but THC-OH and THC-COOH are the most abundant.
- The CYP enzymes involved in THC metabolism are CYP2C9, CYP2C19, and CYP3A4.
- THC-COOH is further metabolized by conjugation with glucuronic acid.
More than 55% of THC is excreted in the feces, mainly as THC-OH. Approximately 20% is excreted in urine mainly as free THC-COOH and THC-COOH glucuronide. In addition to THC-COOH being the predominant metabolite in urine, it also has a long half-life of several days and even weeks in heavy users. This makes it ideal for analysis by confirmatory testing in clinical laboratories. For methods that can distinguish between THC-COOH and THC-OH, correlations can be made concerning how recently marijuana was used. If THC-COOH is detected in the absence of THC-OH, it can be assumed that cannabis use occurred some time ago. If both THC-COOH and THC-OH are detected then consumption was recent, and the user is probably impaired.
THC and THC-COOH are highly lipid soluble, causing them to have a tendency to accumulate in tissues. The slow redistribution back into the bloodstream contributes to THC-COOH’s long half-life.
In confirmatory testing, a sample preparation step referred to as alkaline hydrolysis is used to break the glucuronide bond to convert the conjugated metabolites back to free THC, free THC-COOH, and free THC-OH.
