Fraser Horton
Fraser Horton
Last Updated on September 23, 2021

The cannabis plant contains hundreds of different compounds of which the cannabinoids and terpenes are the most important ones. THC (tetrahydrocannabinol) and CBD (cannabidiol) are the primary cannabinoids largely responsible for the recreational and medicinal properties of the plant. 

Even though most cannabis users know that THC remains in the body for a while because of the way it’s metabolized, not many are familiar with the process itself. Whether weed is consumed via inhalation or ingestion, the body metabolizes THC so it can eliminate it more efficiently. Knowing the phases of this process can help you understand why THC lingers for so long in your system. 

Therefore, in this article, we’ll explain all about how THC is metabolized, from start (when you consume weed) to finish (when you eliminate it).

An Overview of THC

THC (full name delta9-tetrahydrocannabinol or delta9-thc) is the primary psychoactive cannabinoid in the cannabis plant. It causes feelings of bliss, euphoria, and relaxation, also known as getting high. However, THC can also have some anti-inflammatory properties, although this characteristic is more emphasized in CBD.

Cannabinoids, including THC, have a unique way of producing their effects on the body by interacting with the cannabinoid receptors as part of the body’s endocannabinoid system. In particular, these receptors are the CB1 and CB2 receptors located in the central nervous system and the peripheral nervous system and immune cells, respectively.

THC attaches to both types of receptors, although its effects on the CB1 receptors are much more pronounced because a large part of them are found in the brain. THC temporarily alters the function of the receptors which, in turn, influence key parts of the brain, such as mood, motor control, time perception, etc. The intensity of THC is attenuated by CBD, although sometimes too much THC can cause side effects such as anxiety and paranoia.

How THC Gets Activated – The First Conversion

One very important piece of information is that raw cannabis isn’t psychoactive. The cannabinoids in raw cannabis are present in their inactive forms, or acidic precursors, and this applies to all varieties of weed (Cannabis indica and Cannabis sativa).

That being said, the acidic precursor of THC is called THCA (tetrahydrocannabinolic acid). It has the same anti-inflammatory properties as THC, but it’s not psychoactive. So, for example, if you consume raw weed, you won’t get high.

What converts THCA into THC is a chemical process caused either by aging (for example, curing weed) or by coming into contact with heat. This process is called decarboxylation and it’s necessary to make weed psychoactive. 

When you smoke or vape weed, the high temperature is what activates the cannabinoids. Similarly, weed needs to be decarboxylated prior to making edibles like cannabutter or brownies.

How Is THC Metabolized In the Body?

Things get interesting once THC is introduced into the body. First of all, its bioavailability and peak concentration largely depend on the method of consumption (inhalation or ingestion). And second, how it gets metabolized also depends on how you consume it, meaning it takes different metabolic pathways.

In short, when you inhale weed, THC enters the bloodstream directly through the lungs, and then it gets carried to the brain and the rest of the body. When you ingest weed, it goes through the digestive system first, and then to the brain and the other parts of the body. 

In any case, THC must go through the liver to be metabolized and turned into byproducts, also called metabolites, to make it easier to eliminate. Note that THC gets converted into different types of metabolites twice.

On average, it takes about 1.5 hours for THC to be processed when inhaled, and 3.5-10 hours when it’s ingested.

Phase I – Conversion into Metabolites

When THC gets to the liver, the liver enzymes immediately start to metabolize it. THC gets metabolized by the so-called cytochrome P450 system which is a superfamily of enzymes responsible for metabolizing cannabinoids, but also other types of substances (such as alcohol). In particular, THC gets metabolized by the CYP2C9 enzymes, a member of the P450 superfamily.

This part of the conversion process is also called hydroxylation because the enzymes first add a hydrogen molecule and then an oxygen molecule to the structure of THC to make it larger (so it can be more easily eliminated). 

11-OH-THC – The Active Metabolite

During the first conversion, when a hydrogen molecule is added, the resulting metabolite is a modified version of THC called 11-OH-THC (full name 11-hydroxy-delta-9-tetrahydrocannabinol or 11-hydroxy-THC).

The interesting thing about 11-OH-THC is that it’s an active metabolite, meaning that it’s capable of binding to the receptors and just like THC, it’s psychotropic. It’s also thought to produce slightly stronger effects than THC and to be more abundant when you consume weed via oral administration. 

The plasma concentration of this metabolite is higher when ingesting weed than when smoking it because it passes through the liver before it gets to the bloodstream, unlike when you smoke or vape weed. That’s why edibles are said to be way more powerful and longer-lasting than dry herbs.

THC-COOH – The Inactive Metabolite

The same family of enzymes then proceed to further modify the active metabolite 11-OH-THC by oxidation or adding an oxygen molecule to it. The result is the THC metabolite called THC-COOH (full name 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid 11-nor-9-carboxy-THC). This metabolite is the final version of THC before it’s prepared to be eliminated.

THC-COOH is an inactive metabolite, meaning that through this final process, it has lost its ability to bind to the cannabinoid receptors (and it’s no longer psychoactive).

Phase II – Preparing for Elimination 

Once the first phase of the metabolic process is finished, different types of enzymes called UTP enzymes prepare the THC-COOH metabolite for elimination. They do this by attaching a glucuronide molecule to THC-COOH, making it a water-soluble molecule. This means that it’s ready for excretion through urine and feces.

The average half-life of THC metabolites depends on many things, but generally, within five days, 80-90% of THC and its metabolites are eliminated from the body. The remaining metabolites get stored into the adipose tissue (fat storage) in the body because both THC and its metabolites are lipid-soluble. Over time, these compounds will get slowly released and finally eliminated from the body.

Frequent cannabis users and users who consume weed with high THC levels will have accumulated more THC metabolites than infrequent users.

The Most Commonly Used Drug Tests Screen for THC Metabolites

Drug tests (or immunoassays) are commonly used in the workplace to detect drug use, including cannabis because it’s still illegal on a federal level. Since THC metabolites linger for a period of time in your system, it makes sense that the most commonly used drug tests look for THC metabolites instead of THC itself.

The concentration of THC metabolites is detected by specific confirmation methods such as gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS).

For example, the urine test is designed to measure the concentrations of THC metabolites in your urine sample. Similarly, the hair follicle test also looks for THC byproducts. These two types of drug tests are used to detect the habitual use of cannabis.

On the other hand, blood tests and oral fluid (saliva) tests are designed to look for THC itself to discover either current impairment or very recent marijuana use (up to 3 days).

Conclusion – The Metabolism of THC Is Complex

Whether you use recreational or medical cannabis, you must be aware that due to the complex metabolism of THC, its byproducts remain in the body for a long period of time. The liver enzymes convert THC to its metabolites twice in order to make it easier to eliminate from the body, but despite this, there is still a small percentage of THC metabolites that stay behind and get stored into the fatty tissue. 

Additional Sources

Grotenhermen F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clin pharmacokinet, 42(4), 327–360. https://doi.org/10.2165/00003088-200342040-00003

Farokhnia, M., McDiarmid, G. R., Newmeyer, M. N., Munjal, V., Abulseoud, O. A., Huestis, M. A., & Leggio, L. (2020). Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study. Translational psychiatry, 10(1), 71. https://doi.org/10.1038/s41398-020-0756-3 

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. British journal of clin pharmacol, 84(11), 2477-2482.

Huestis MA (2007). Human cannabinoid pharmacokinetics. Chemistry & biodiversity, 4(8), 1770–1804. https://doi.org/10.1002/cbdv.200790152 

Pertwee R. G. (2006). The pharmacology of cannabinoid receptors and their ligands: an overview. International journal of obesity (2005), 30 Suppl 1, S13–S18. https://doi.org/10.1038/sj.ijo.0803272

Sharma, P., Murthy, P., & Bharath, M. M. (2012). Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iranian journal of psychiatry, 7(4), 149–156.

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