When you consume cannabis, either through smoking or eating, the 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 you eat edible marijuana foods, they follow the first-pass effect and enter the liver. The liver is the body's source of energy and it metabolizes cannabis, producing cannabinoids as a result.
Once THC and CBD enter the blood and brain, there is no change in meaning and beneficial or harmful effects appear. Research has found that, while both compounds produced similar psychoactive effects, 11-hydroxy-THC became more rapidly activated. Inhaled THC undergoes a different metabolic process because, instead of passing through the stomach and then through the liver, THC travels directly to the brain. According to the theory, once released into the bloodstream, 11-hydroxy-THC more easily crosses what is known as the blood-brain barrier.
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). Other CYP3A4 inhibitors, such as clarithromycin, erythromycin, cyclosporine, verapamil, itraconazole, voriconazole and boceprevir, are expected to produce similar increases in THC concentrations. When marijuana is ingested rather than inhaled, the liver metabolizes tetrahydrocannabinol (THC) and is converted to 11-hydroxytetrahydrocanibinol (11-OH-THC), leaving many users with health problems related to possible long-term damage to the bile ducts and liver function. Tetrahydrocannabinol (THC) is a cannabinoid that causes a euphoric and intoxicating effect, while cannabidiol (CBD) is responsible for therapeutic effects.
Much of the scientific research on 11-hydroxy-THC is older and focuses more on its ability to be detected in urine samples and blood tests, as well as on bioavailability, rather than on its psychoactivity. It could be that some people only have naturally high tolerances or their digestive system processes THC differently. When you ingest THC by mouth, this powerful cannabinoid travels through the digestive system and eventually reaches the liver where it breaks down into molecules called metabolites. The liver can be so good at breaking down foreign compounds that it breaks down too much of the edible's THC to produce an effect.
Based on genetic studies, CYP2C9 inhibitors are expected to increase the plasma concentration of THC. Ketoconazole, an inhibitor of CYP3A4, 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 with greater increases in the concentration of its metabolites. In addition, the metabolism of THC in the liver requires a certain enzyme so if someone doesn't feel anything their tolerance is extraordinarily high or they have so little of that enzyme in their body that edibles are not an effective method for them.