The Ultimate Guide to Marijuana Metabolism

This article summarizes scientific research on how our body processes and stores marijuana, visualized and explained in simple language.

What Will You Learn

  • What happens to weed in the body.
  • Understand the pathway of THC in the human body.
  • How marijuana metabolites are stored.
  • How these metabolites are excreted.

Marijuana metabolism scheme

Summary

The pathway of marijuana in our body can be split into 3 phases:

  • Consumption – this is what happens when we consume weed
  • Metabolism – this is how our body processes weed components
  • Excretion – this is how marijuana metabolites are removed from the body

We will describe each of these phases. Here’s the brief summary:

When we smoke, THCA in weed is decarboxylated and becomes THC.

THC gets into the lungs and then into the blood. From the blood, it gets into the liver, where it is metabolized in 2 phases. Then it’s released out of the body via urine and feces.

Consumption

THCA (tetrahydrocannabinolic acid) is a cannabinoid found in raw and live cannabis. It’s not psychoactive and doesn’t cause a “high” effect.

As the plant dries, THCA slowly converts to THC (delta-9-tetrahydrocannabinol). The process of converting THCA to THC is called decarboxylation.

During decarboxylation (decarbing), the carbon dioxide molecule is removed from THCA, becoming psychoactive THC.

Heat hastens this process.

As THCA becomes THC when we smoke, the THC travels into the lungs and next to the blood.

According to the study, we inhale only about 50% of the formed THC. 30% is destroyed by burning. Others are lost in sidestream and incomplete absorption in the lungs.

Then only a small proportion reaches body circulation due to what is called the first-pass metabolism.

As a result, only 25-30% of smoked THC gets into the blood. Studies show that heavy users receive ~25% of THC while occasional users get ~12% of THC. That’s because heavy users are able to smoke more efficiently.

amount of THC lost

With the blood, the THC travels to the heart and then to the brain, where the high effects occur.

Only about 1% of THC gets into the brain.

With the blood it gets into the liver and undergoes 2 phases of metabolism. Then
it is released via feces and urine.

How the THC is stored in the body

THC and some of its metabolites are fat-soluble. Meaning, they can dissolve in fats or oils.

THC rapidly penetrates highly vascularized tissues like lungs, liver, heart, body fat.

About 70% of the THC is taken up by tissues(mostly by body fat), and 30% are metabolized.

Then, THC is slowly released back into the blood from fat. So THC is continuously moving from fat into the blood and back again.

THC distribution chart

 

Metabolism

There are two phases of marijuana metabolism in the liver.

During these phases, cytochromes P450 convert THC to 11-Hydroxy-THC and then into 11-nor-9-carboxy-THC. After that, these metabolites are marked for excretion out of the body.

Cytochromes P450 are the major enzymes involved in drug metabolism.

Phase 1

At this phase, CYP2C9 enzymes convert THC to 11-OH-THC ( 11-Hydroxy-THC ).

Then, CYP2C19 and CYP3A4 enzymes convert 11-OH-THC to 11-COOH-THC (11-Nor-9-carboxy-thc).

THC phase 1 metabolism

Phase 2

During this phase, THC metabolites are prepared for excretion. UGT enzymes add a glucuronide molecule to metabolites. This process is called glucuronidation.

11-COOH-THC is metabolized mostly by the UGT1A3 enzyme and forms THC-COO-Gluc. In comparison, 11-OH-THC is metabolized mainly by UGT1A9 and UGT1A10 enzymes and forms THC-O-Gluc.

These metabolites are soluble in water. Therefore, they are dissolved in the bile and water and excreted via urine and feces.

THC phase 2 metabolism

Excretion

Most of the metabolites are excreted with the feces, about 65%.

About 20% of metabolites are excreted in the urine.

The remaining 15% are reabsorbed back into the blood from the kidneys and gastrointestinal tract.

Excretion By Kidneys

11-COOH-THC is the primary metabolite excreted in the urine and detected by drug tests.

It’s excreted in the form of THC-COO-Gluc.

Part of the metabolites is reabsorbed back to the blood through the process called tubular reabsorption.

Tubular reabsorption is the process that moves solutes and water out of the pre-urine back into your bloodstream.

tubular reabsorbtion

Biliary Excretion

After 11-OH-THC is converted to THC-O-Gluc, it becomes water-soluble and is dissolved in the bile.

With bile, it goes into the gastrointestinal tract.

Part of THC-O-Gluc is reabsorbed back into the blood through the process called enterohepatic circulation.

The remaining metabolites are excreted with the feces.

THC enterohepatic circulation