When you consume marijuana, the main psychoactive compound, THC, is processed primarily by your liver into a series of metabolites, some active and some inactive, before being slowly eliminated from your body. The process is surprisingly complex, and it explains everything from why edibles hit differently than smoking to why THC can show up on a drug test weeks after your last use.
What Happens in the Liver
THC metabolism centers on two liver enzyme families called CYP2C9 and CYP3A4. These enzymes break THC down in a two-step sequence. First, they convert THC into a metabolite called 11-OH-THC. This intermediate product is still psychoactive. In fact, when researchers gave subjects equal intravenous doses of THC and 11-OH-THC, the metabolite produced a noticeable high within 3 to 5 minutes, while THC itself took 10 to 20 minutes to peak. That faster, potentially stronger effect from 11-OH-THC is a key reason edibles can feel more intense than smoking.
In the second step, the liver converts 11-OH-THC into THC-COOH, a compound that has no psychoactive effects at all. THC-COOH is the metabolite that standard urine drug tests detect, which is why a positive test indicates past cannabis use but says nothing about whether someone is currently impaired.
Why Edibles and Smoking Feel So Different
The route THC takes into your body dramatically changes how much of it your liver processes before it ever reaches your brain. When you smoke or vape, THC passes from your lungs directly into your bloodstream, largely bypassing the liver on its first pass through the body. Bioavailability through inhalation ranges from about 10% to 35% of the THC in the product, but the THC that does enter your blood gets to your brain quickly and relatively intact.
Edibles tell a different story. Swallowed THC must pass through your digestive tract and then through the liver before entering general circulation. This is called first-pass metabolism, and it’s extensive. Oral bioavailability of THC can be as low as 6%, meaning the liver eliminates the vast majority of the THC before it ever circulates. But here’s the catch: a large portion of that THC gets converted into 11-OH-THC, the psychoactive metabolite that produces effects faster and possibly more intensely than THC itself. So you absorb less total compound, but a higher proportion of what you do absorb is the more potent metabolite. This is why edibles often produce a stronger, longer-lasting, and sometimes unexpectedly intense experience.
Storage in Body Fat
THC is highly lipophilic, meaning it dissolves readily in fat. After entering your bloodstream, THC is rapidly absorbed into fatty tissues throughout the body. In human studies, THC has been detected in fat biopsies up to 28 days after the last exposure. Animal research shows that gonadal fat accumulated THC at higher concentrations than the liver, brain, lungs, or other fatty tissue, and with repeated dosing, THC levels in fat tissue built up significantly over time.
Under normal conditions, stored THC passively diffuses back out of fat cells and into the bloodstream at a slow, steady rate. This is why frequent users have such a long elimination window. THC binds to triglycerides inside fat cells, and when those triglycerides are broken down during normal fat metabolism, THC is released back into circulation. Periods of enhanced fat burning, such as intense exercise, fasting, or stress, may accelerate this release. In animal models, conditions that triggered lipolysis (fat breakdown) pushed stored THC back into the blood at higher-than-normal concentrations.
Enterohepatic Recycling
THC’s metabolism isn’t a one-way trip. A process called enterohepatic circulation recycles a portion of THC metabolites back through your system. After the liver processes THC, some metabolites are excreted into bile, which flows into your intestines. There, a fraction gets reabsorbed into the bloodstream and sent back to the liver for another round of processing. Studies in animals suggest that 10 to 15% of a THC dose gets recycled this way. In humans, this recycling sometimes produces a noticeable second peak in blood THC levels. Combined with the slow release from fat stores, enterohepatic circulation contributes to THC’s remarkably long terminal half-life, which has been reported at greater than 4.1 days in chronic users.
How Your Genetics Affect the Process
Not everyone metabolizes THC at the same rate. The CYP2C9 enzyme, one of the two main enzymes responsible for breaking down THC, comes in several genetic variants. The most significant are the *2 and *3 variants, which reduce the enzyme’s activity. If you carry one or two copies of these variants, your body clears THC more slowly, leading to higher and longer-lasting blood levels of both THC and its active metabolite 11-OH-THC.
The effect is substantial. People with the CYP2C9*3 variant showed roughly a threefold increase in THC exposure after an oral dose compared to people with normal enzyme activity. Clinically, this translated into greater sedation. For people who carry these variants (and the frequency varies by ethnic background), the same dose of an edible could produce dramatically stronger effects than it would for someone with fully active enzymes. In medical cannabis contexts, clinicians recommend that carriers of these variants start with lower doses and increase gradually.
How THC Leaves Your Body
THC and its metabolites exit the body through two main routes. Roughly 65% is excreted through feces, while about 20% leaves through urine. The remaining percentage exits through other minor pathways. The metabolite profile differs by route: fecal excretion contains a mix of both 11-OH-THC (about 21%) and THC-COOH (about 28%), while urine primarily contains THC-COOH in a form that has been further processed by the body for easier elimination.
The practical timeline for complete elimination varies enormously based on how often you use cannabis. A single use may clear to undetectable levels in urine within a few days. Regular use extends that window considerably. Heavy, chronic users have tested positive for THC-COOH in urine up to 77 days after their last use, a reflection of how much THC accumulates in fat tissue over time and how slowly it trickles back out. This is why marijuana stands apart from most other substances in drug testing: its unique fat solubility creates a detection window measured in weeks rather than hours or days.