Cannabis is metabolized primarily in the liver, where enzymes convert THC and other cannabinoids into a series of breakdown products, some of which are psychoactive themselves. The process follows the same two-phase pattern your body uses for most drugs: first oxidizing the compounds into new forms, then making those forms water-soluble enough to excrete. Understanding this pathway explains why edibles hit harder than smoking, why cannabis can interact with common medications, and why THC can show up on a drug test weeks after your last use.
How the Liver Breaks Down THC
When THC reaches the liver, two enzymes from the cytochrome P450 family do most of the initial work: CYP2C9 and CYP3A4. These enzymes add an oxygen atom to the THC molecule, converting it into a metabolite called 11-hydroxy-THC (11-OH-THC). This first metabolite is still psychoactive. In fact, it crosses into the brain more rapidly and in greater quantities than THC itself, which is a key reason oral cannabis tends to produce stronger, longer-lasting effects than inhaled cannabis. When you smoke or vape, THC goes straight to the brain through the lungs and largely bypasses this conversion step. When you eat an edible, the liver processes a much larger share of the THC before it ever reaches your bloodstream.
CYP2C9 then takes 11-OH-THC one step further, oxidizing it into THC-COOH (11-nor-9-carboxy-THC). This second metabolite is inactive, meaning it produces no high. THC-COOH is also the compound that standard drug tests look for, because it lingers in the body far longer than THC or its active metabolite.
Why Edibles Feel Different
The difference between smoking and eating cannabis comes down to how much 11-OH-THC your liver produces. After inhalation, THC enters the bloodstream through the lungs and reaches the brain within seconds, largely in its original form. Only a fraction gets converted to 11-OH-THC on subsequent passes through the liver. With edibles, nearly all the THC passes through the liver first, generating much higher levels of 11-OH-THC relative to the parent compound.
Research in rats found that 11-OH-THC enters the brain at a higher rate than THC itself, with brain extraction of about 67-70% for the metabolite compared to 59-66% for THC. The larger presence of 11-OH-THC in brain tissue helps explain why edibles often feel more intense and longer-lasting, even at similar doses.
Phase II: Preparing for Excretion
Once the liver has created THC-COOH and other oxidized metabolites, a second round of processing makes them water-soluble enough to leave the body. Enzymes called UDP-glucuronosyltransferases attach a sugar molecule (glucuronic acid) to the metabolites in a process called glucuronidation. This happens to THC itself, to 11-OH-THC, and to THC-COOH, producing three distinct glucuronide conjugates. These water-soluble forms can then be filtered by the kidneys into urine or secreted by the liver into bile and eventually into feces.
More than 65% of cannabis metabolites leave the body through feces, while roughly 20% are excreted in urine. The primary metabolite found in urine is the glucuronide form of THC-COOH, which is what urine drug tests detect. In feces, 11-OH-THC is the predominant form.
How Long Metabolites Stay in Your System
THC itself clears from the blood relatively quickly, but THC-COOH is a different story. Because it’s fat-soluble, it gets stored in body fat and released slowly over time. For occasional users, THC-COOH has a half-life of 20 to 57 hours. For regular users, that half-life stretches to 3 to 13 days, meaning it takes that long just for half the stored metabolite to clear. This is why heavy, daily users can test positive on a urine screen for a month or more after stopping, while someone who used once might clear a test in a few days.
The wide range in these numbers reflects differences in body fat percentage, metabolism, frequency of use, and the potency of cannabis consumed. More body fat means more storage capacity for THC-COOH, and more frequent use means those fat stores are more saturated.
How CBD Is Metabolized
CBD follows a similar liver pathway but uses a slightly different set of enzymes. CYP2C19 is the primary enzyme responsible for converting CBD into its main active metabolite, 7-hydroxy-CBD (7-OH-CBD), contributing about 69% of this conversion. CYP2C9 handles the remaining 31%. The active metabolite 7-OH-CBD has roughly the same pharmacological potency as CBD itself. It’s then further oxidized into 7-carboxy-CBD, which is inactive.
CYP3A4 also plays a major role in CBD metabolism, but through different chemical pathways that produce various hydroxylated forms at other positions on the molecule. Like THC metabolites, CBD and its breakdown products also undergo glucuronidation to become water-soluble for excretion.
Minor Cannabinoids Follow Similar Paths
Cannabinol (CBN), the cannabinoid that forms as THC ages and degrades, is metabolized by CYP2C9 and CYP2D6 rather than CYP3A4. Molecular modeling shows that CBN fits into the CYP2C9 enzyme in a very similar orientation to THC, with the same carbon atom (C11) positioned close to the enzyme’s active iron center. This is why both compounds produce 11-hydroxy metabolites as their primary breakdown products. Cannabigerol (CBG) and cannabichromene (CBC) are also rapidly converted by CYP enzymes, but into structurally distinct metabolites with different pharmacological effects than their parent compounds.
Drug Interactions From Enzyme Inhibition
Because THC and CBD are both processed by, and also block, several of the same liver enzymes that metabolize common medications, cannabis use can alter how other drugs work in your body. This is one of the most clinically significant consequences of cannabis metabolism.
THC inhibits CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP2D6. CBD inhibits all of those plus CYP3A4. When these enzymes are partially blocked, medications that depend on them are broken down more slowly, effectively increasing their levels in the bloodstream. Even THC’s own metabolites contribute: 11-OH-THC and the glucuronide form of THC-COOH inhibit CYP2B6, CYP2C9, and CYP2D6.
The practical consequences can be serious for certain medications:
- Blood thinners like warfarin: Metabolized by CYP2C9. Clinical reports have documented increased anticoagulant effects in cannabis users, raising the risk of bleeding.
- Anti-seizure medications like phenytoin: Also a CYP2C9 substrate. Case reports describe severe adverse effects when combined with cannabis.
- Antidepressants, antipsychotics, opioids, and beta blockers: Many of these are metabolized by CYP2D6, which handles about 25% of commonly prescribed drugs. Cannabis use can slow their clearance and intensify side effects.
- Tamoxifen: This breast cancer drug relies on CYP2D6 to convert it into its active form. Cannabis use has been associated with lower blood levels of the active metabolite, potentially reducing the drug’s effectiveness.
CBD poses a particularly broad interaction risk because it inhibits CYP3A4 in addition to the enzymes THC affects. CYP3A4 is the single most important drug-metabolizing enzyme in the liver, responsible for processing a large share of all pharmaceuticals. This is why CBD products carry interaction warnings for a wide range of medications, and why the interaction risk from CBD is generally considered greater than from THC alone.