From the Guidelines
THC is primarily metabolized by the liver through the process of first-pass metabolism into 11-hydroxytetrahydrocannabinol. This process occurs when THC is absorbed into the bloodstream from the gut and transported to the liver, where it undergoes metabolism 1. The liver's role in metabolizing THC is crucial, as it transforms THC into more water-soluble metabolites, including 11-hydroxytetrahydrocannabinol, which is the main psychoactive metabolite. Some key points to consider about THC metabolism include:
- The liver's first-pass metabolism of THC creates a longer latency to onset of drug effect than with inhaled cannabis 1
- THC metabolism can be affected by various factors, including genetic variations and the method of cannabis consumption 1
- Understanding the metabolic pathway of THC is important for determining the duration of cannabis effects and how long THC remains detectable in drug tests. The unique pharmacokinetics of edible cannabis, which involves first-pass metabolism in the liver, can lead to higher blood concentrations of 11-hydroxytetrahydrocannabinol and a greater risk of overconsumption 1.
From the Research
Metabolism of THC
- THC is metabolized in the liver, where it is converted into various metabolites, including 11-OH-THC and 11-COOH-THC 2
- The metabolism of THC is determined by the route of consumption, with inhaled THC achieving peak levels in the bloodstream within 6 to 10 minutes 2
- The bioavailability of inhaled THC is 10% to 35%, while the bioavailability of ingested THC is only 4% to 12% 2
Enzymes Involved in THC Metabolism
- CYP2C9 is the primary enzyme responsible for the hydroxylation of THC to 11-OH-THC 3, 4
- CYP2C19 and CYP3A4/5 also contribute to the metabolism of THC, forming other hydroxylated metabolites 4
- CYP1A2, CYP2B6, and CYP2D6 are also inhibited by THC and its metabolites, which could lead to drug-drug interactions 5
Role of FABP1 in THC Metabolism
- FABP1 (fatty acid binding protein 1) plays a crucial role in the transport and biotransformation of THC in the liver 6
- FABP1 binds to THC and facilitates its transport to cytochrome P450 enzymes for metabolism 6
- The presence of FABP1 alters the metabolism of THC by recombinant CYPs and human liver microsomes in an enzyme- and metabolite-specific manner 4