How is THC Metabolized?

The cannabis plant makes several hundred distinct compounds ^{3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications} — but the one almost everyone is asking about is THC (Δ9-tetrahydrocannabinol), the molecule responsible for the “high.”

What actually happens to THC once it’s in you is more interesting than the folklore suggests. The same dose can hit in seconds or in hours; it can feel sharp and brief or slow and heavy; and it can show up on a drug test weeks after the effects wore off. All of that comes down to metabolism — how the body absorbs THC, switches it on, parks it in fat, and eventually clears it.

This guide walks through that whole journey, and clears up a few things the older internet gets wrong along the way — including which metabolite actually gets you high.

What Is a Cannabinoid?

Every one of us is born with an endocannabinoid system (ECS) — a signalling network the body uses to keep things in balance. It has a hand in mood, memory, pain, appetite, sleep, immune activity, and body temperature ^{3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications12Reference 12Pertwee RG · 2008The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin}. It runs on the body’s own “endocannabinoids,” chiefly anandamide and 2-AG ^{12Reference 12Pertwee RG · 2008The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin}.

THC works because it’s shaped enough like those natural signals to plug into the same receptors. There are two main ones:

• CB1 receptors sit mostly in the brain and nervous system. This is where THC produces its psychoactive effects — the changes in mood, memory, perception, appetite, and pain ^{3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications12Reference 12Pertwee RG · 2008The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin}.
• CB2 receptors sit mainly in peripheral and immune tissue, such as the spleen and immune cells ^{3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications12Reference 12Pertwee RG · 2008The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin}.

One important nuance: THC is a partial agonist at both receptors ^{12Reference 12Pertwee RG · 2008The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin} — it nudges them rather than flooring the accelerator. That partial, indirect action is part of why cannabis effects are so dose- and person-dependent.

The Pathway: From Raw Plant to Excreted Waste

THC’s transformation happens in a clear sequence of steps. Only two of the molecules in this chain are psychoactive — and it’s a common mistake to point at the wrong ones.

Step 1 — Decarboxylation: Metabolism Starts Outside the Body

In the living plant, THC doesn’t exist in its active form at all. It’s stored as THCA (Δ9-tetrahydrocannabinolic acid), which is not intoxicating. Applying heat drives off its carboxyl group as carbon dioxide — a reaction called decarboxylation — converting it into active Δ9-THC ^{11Reference 11Wang M et al. · 2016Decarboxylation study of acidic cannabinoids: a novel approach using ultra-high-performance supercritical fluid chromatography/photodiode array-mass spectrometry}.

This is why raw cannabis doesn’t get you high, but smoked, vaped, or baked cannabis does. Combustion and vaporisation are hot enough to do it essentially instantly; gentle baking works too, just more slowly. Lab kinetics give a sense of the trade-off: THCA converts in roughly 30 minutes at 110 °C, ~9 minutes at 130 °C, and ~6 minutes at 145 °C — hotter is faster ^{11Reference 11Wang M et al. · 2016Decarboxylation study of acidic cannabinoids: a novel approach using ultra-high-performance supercritical fluid chromatography/photodiode array-mass spectrometry}.

Step 2 — The Metabolite That Also Gets You High: 11-OH-THC

Here’s the correction the old internet needs. Once Δ9-THC reaches the liver, enzymes hydroxylate it into 11-OH-THC (11-hydroxy-THC) — and this metabolite is psychoactive in its own right, roughly equipotent with THC itself in humans ^{1Reference 1Grotenhermen F · 2003Pharmacokinetics and pharmacodynamics of cannabinoids2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics5Reference 5Grotenhermen F · 2004Clinical pharmacodynamics of cannabinoidsView study →6Reference 6Perez-Reyes M et al. · 4049Perez-Reyes M, Timmons MC, Lipton MA, Davis KH, Wall ME. Intravenous injection in man of Δ9-tetrahydrocannabinol and 11-OH-Δ9-tetrahydrocannabinol. Science. 1972;177(4049):633–635.}. It’s not the body switching THC off; it’s the body making a second active molecule.

It’s only the next step that deactivates things: 11-OH-THC is oxidised further into THC-COOH (11-nor-9-carboxy-THC), which is inactive ^{1Reference 1Grotenhermen F · 2003Pharmacokinetics and pharmacodynamics of cannabinoids2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics}. THC-COOH is then tagged with a sugar group (glucuronidation, by UGT enzymes) to make it water-soluble enough to excrete ^{10Reference 10Mazur A et al. · 2009Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids}.

So the chain is: inactive acid → active THC → active 11-OH-THC → inactive THC-COOH → excreted conjugate. Two active molecules, not one — which matters enormously once we compare routes.

Inhaled vs Oral: Why the Same Drug Feels So Different

Most people notice that smoking and edibles are almost different experiences. That isn’t in your head — it’s pharmacokinetics.

1. Inhalation

When you smoke or vaporise, Δ9-THC crosses the lungs and appears in the blood within seconds, peaking in about 3–10 minutes ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}. Effects build a little behind that plasma peak, maxing out around 10–30 minutes ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics}, then taper over a couple of hours. Because THC is absorbed straight into circulation, it mostly bypasses the liver’s first pass — so relatively little 11-OH-THC is made (only about 10% of the THC level) ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics}. Fast, sharp, and comparatively short.

2. Oral Ingestion

Eat THC and the story changes. It has to survive the stomach, be absorbed through the gut, and travel to the liver before it reaches the rest of the body. That’s slower — effects can take 1–2 hours (sometimes longer) to arrive, but they’re steadier and last longer ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}.

The catch is that first liver pass. On the way through, a large fraction of THC is converted to 11-OH-THC — so much that oral doses can produce more 11-OH-THC than THC itself ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics4Reference 4Schwilke EW et al. · 2009Schwilke EW, Schwope DM, Karschner EL, et al. Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Clin Chem. 2009;55(6):1177–1187. PMID 19833841.}. Since 11-OH-THC is fully psychoactive, edibles deliver a different blend of active molecules than smoking does. That — not some mythical “stronger THC” — is the real reason edibles feel more intense and more body-heavy, and why they’re so easy to overdo. The trade-off for that potency is a much lower overall bioavailability (~4–12%), because first-pass metabolism also destroys a big share of the dose ^{1Reference 1Grotenhermen F · 2003Pharmacokinetics and pharmacodynamics of cannabinoids3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}.

Why THC Lingers: Stored in Your Fat

THC is strongly fat-soluble (lipophilic). The moment blood levels are high, it diffuses out of the blood and into fatty tissue throughout the body — and into the brain, itself a fatty organ. Its volume of distribution is large (on the order of ~10 L/kg) precisely because so much leaves the blood to sit in tissue ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}.

Then the process runs in reverse. As blood THC falls, the drug slowly diffuses back out of fat into circulation, to be metabolised bit by bit. This slow release is why THC’s elimination half-life is so long and so variable — measured in days, and longer the more regularly someone uses:

It’s also the source of a persistent myth. THC being “in your system” for weeks does not mean you’re impaired for weeks — the effects are long gone. What lingers is mostly the inactive metabolite THC-COOH, slowly trickling out of fat stores. (A small note: THC circulates almost entirely in blood plasma, where it is ~95–99% bound to lipoproteins — not, as older articles claim, “90% protein-bound.” The 90% figure refers to something else: the split of THC between plasma and red blood cells ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}.)

The Liver’s Role — And Drug Interactions

The heavy lifting of metabolism happens in the liver, through cytochrome P450 enzymes. Two matter most:

• CYP2C9 is the main enzyme that hydroxylates THC into active 11-OH-THC ^{7Reference 7Watanabe K et al. · 2007Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes}.
• CYP3A4 handles oxidation at other positions on the molecule ^{7Reference 7Watanabe K et al. · 2007Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes}.

Because those enzymes are the bottleneck, genetics and co-medications can shift how you respond. People carrying the low-activity CYP2C9*3 variant clear THC more slowly — one study found roughly 3× higher THC exposure and a trend toward greater sedation ^{9Reference 9Sachse-Seeboth C et al. · 2009Interindividual variation in the pharmacokinetics of Δ9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9}. And in principle, strong CYP3A4/2C9 inhibitors (e.g. ketoconazole) can raise THC levels while inducers (e.g. rifampin) lower them — though the clinical size of these interactions in everyday use isn’t fully established, so this is worth awareness rather than alarm ^{8Reference 8Stout SM · 2014Systematic reviewExogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review}.

(For contrast: alcohol is handled by an entirely different enzyme family — alcohol dehydrogenase — not the P450 system.)

Excretion: How THC Finally Leaves

Once THC is fully broken down and made water-soluble, it’s excreted two ways. The larger share — roughly 65–80% — leaves in the stool, and about 20–35% in the urine ^{1Reference 1Grotenhermen F · 2003Pharmacokinetics and pharmacodynamics of cannabinoids3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}. The predominant form differs by route: 11-OH-THC dominates in feces, while THC-COOH (as its glucuronide) dominates in urine ^{2Reference 2Huestis MA · 2007Human cannabinoid pharmacokinetics3Reference 3Sharma P et al. · 2012Chemistry, metabolism, and toxicology of cannabis: clinical implications}. That urinary THC-COOH-glucuronide is exactly what a standard drug test looks for — which is why tests detect past use, not current intoxication.

The Bottom Line

THC’s effects are shaped less by the plant than by your own metabolism. Heat activates it; the liver both sustains the high (via active 11-OH-THC) and eventually ends it (via inactive THC-COOH); your fat stores stretch the timeline; and the route you choose decides whether all of that unfolds in minutes or hours. Understanding that chain explains almost every practical question people have — why edibles creep up on you, why the high fades long before a drug test clears, and why the same dose lands so differently from one person to the next.