THC and other cannabinoids are eventually absorbed and partially metabolized by the liver before entering the bloodstream and reaching the brain. This process of absorbing cannabinoids is much slower than smoking. When edible marijuana products are ingested, they produce the first-pass effect and enter the liver. The liver is the body's source of energy, and it metabolizes cannabis to produce cannabinoids as a result of hepatic metabolism.
Once THC and CBD enter the blood and brain, there is no change of direction and they can have either a beneficial or harmful effect. Inhaled THC undergoes a different metabolic process because, instead of passing through the stomach and then through the liver, it travels directly to the brain. Some people may naturally have high tolerances or their digestive system may process THC more efficiently. Other CYP3A4 inhibitors, such as clarithromycin, erythromycin, cyclosporine, verapamil, itraconazole, voriconazole and boceprevir, can also increase THC concentrations.
The metabolite 11-hydroxy-THC has been found to have more profound effects than THC itself. This is due to its ability to cross the blood-brain barrier more easily than THC. Delta-10 THC is an isomer of THC that has similar chemical properties but does not have the same effects. Cannabidiol (CBD) is also a substrate for CYP3A4 and CYP2C19, and ketoconazole and rifampicin can increase or decrease its concentration respectively.
THC-O is an unnatural cannabinoid that has not been studied thoroughly and can be dangerous. When you eat foods that contain Δ9-tetrahydrocannabinol (THC), the liver converts approximately 50% of activated THC to 11-hydroxytetrahydrocannabinol (11-OH-THC or 11-hydroxy-THC). This metabolite is particularly effective at crossing the blood-brain barrier, which produces a more intense effect. A certain enzyme is needed to metabolize THC in the liver, so if someone does not feel anything after ingesting it, they may have an unusually high tolerance or lack this enzyme in their body.
CYP2C9 inhibitors are expected to increase the plasma concentration of THC as well. Much of the scientific research on 11-hydroxy-THC focuses on its bioavailability rather than its psychoactivity. However, anecdotal evidence suggests that 11-hydroxy-THC has four times stronger psychoactive effects than THC.
