THC metabolism

Cannabis is a slurry of over 421 chemicals [6] that each exert different effects on the body. Macros such as carbohydrates, fiber, protein, and lipids are present in high amounts, as well as trace minerals and vitamins. The main components, however, in the cannabis plant that most people are interested in, are the cannabinoids, of which there are about 61 (Sharma, Murthy, and Bharath 2012).

THC is the main psychoactive cannabinoid found in the Cannabis genus, but how is it processed within the body? And what are the differences in this process when eaten, or smoked/vaporized? We will discuss this further below.

A close up of the THC containing trichomes on the bud (flower) of a cannabis plant. (Cannabis Culture, 2009)

A close up of the THC containing trichomes on the bud (flower) of a cannabis plant. (Cannabis Culture, 2009)

What is a cannabinoid?

In every one of us, there exists what is called the “endocannabinoid” system. Endo (relating to endogenous) means “within”, so this really just means the “cannabinoid system within”. It is a natural part of our anatomy that is involved in a huge number of functions.

When we consume exogenous-cannabinoids (cannabinoids from outside the body) such as from the cannabis plant, these chemicals interact with this system to exert its effects.

Cannabinoid receptors (CB) can be found throughout the body. CB1 is mainly found in the brain where it interacts with various neurotransmitters to control appetite, pain-sensation, mood, and memory. CB2, on the other hand, is found in the peripheral tissues (outside the brain) such as the spleen and offers immune system support [4].
 

How is it metabolised within the body?

Cannabinoids generally enter the body in 2 ways: inhalation, where absorption occurs in the lungs, or orally where the absorption occurs in the small intestine. It can also be injected or used as an enema, but these routes are less common.

Depending on where these chemicals are absorbed, is what determines which process it needs to go through to be used and excreted from the body. Both, however, ultimately result in metabolism taking place mainly in the liver.

The  phytocannabinoid acid (phyto refers to plant sourced) (Δ9-THC-Acid) is the inactive form found in the fresh plant. Once burned it becomes “decarboxylated” and forms the active Δ9 THC. In this process, the acid group is broken off to form Δ9 THC.

This can also be achieved by heating the plant in other ways such as baking. This Δ9 THC molecule is responsible for many of the psychoactive effects. It is then metabolized into the active form 11-OH-THC (11-hydroxy-Δ9-THC), which mimics the effects of Δ9 THC in the body and has very similar effects on the brain. Further breakdown then occurs to produce THCCOOH (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) which is considered the inactive metabolite. [6].

It should be noted that there are other metabolites produced as well, but in much less amounts. 

It should be noted that there are other metabolites produced as well, but in much less amounts. 

Inhalation:

During pyrolysis (smoking), over 2000 chemicals are produced as the constituents are basically ripped apart and oxidized [6]. Δ9-THC is absorbed very quickly in the lungs and reaches a high concentration in the blood almost immediately. It is then spread throughout the body through the blood plasma (90%). Δ9-THC is detectable in the blood within seconds after inhalation, and peaks within 3-10 minutes. The breakdown of the constituents are as follows:
 

THC metabolism inhalation

Oral Ingestion:

Oral consumption of activated (decarboxylated) Δ9-THC is much slower than inhalation. The decarboxylated Δ9-THC must first travel through the digestive system, where it is then absorbed through the small intestine (likely into the lymph), from there it travels up the lymph and is deposited at the thoracic duct into the bloodstream where it goes to the liver to be processed. This means it has more steps, and on top of that, each step takes longer. Making the effects come on much slower but at a more steady pace. 

Δ9-THC is then converted to 11-OH-THC very quickly (much faster than by the inhalation route). It is found in higher concentrations from oral ingestion than from inhalation [6] . As the THC is deposited into the blood it tends to penetrate into fat tissues (such as the brain which is roughly 60% fat) [2], and adipose tissues (fat storage) throughout the body which reduces the concentration of THC in our blood. Over time, this THC is redistributed into the blood as levels drop. 

Due to the fact that our fat absorbs THC when we have high amounts of it in our blood, and lets it go when we have less, THC can be seen in our bodies for a long time after the effects have worn off.

Metabolism peaks of THC after oral ingestion

Here is a diagram showing the diffusion of THC into our fat cells when blood concentrations are high, only to be diffused back into the blood when concentrations are low again.

Adipose tissue storage of THC

Processing in the liver

The liver converts  Δ9-THC into its metabolites (11-OH-THC, and THCCOOH) through the same enzymes that process alcohol (cytochrome P450 (CYP) complex). [6]. 

 

Excretion of Cannabis

Roughly 65% of cannabis metabolites are excreted fecally, and the rest through urine. 11-OH-THC is the predominant form in feces, and THCCOOH is found in higher concentration in urine [6]. 

 

In Conclusion

THC metabolism goes through the same steps whether ingested or inhaled, but the duration and speed of delivery can vary greatly.

By inhaling THC, the effects are felt almost immediately, where it is then broken down into the second metabolite over the course of 15 minutes. The secondary metabolite is still highly active, and is broken down over the next few hours to the third and inactive metabolite THCCOOH (which peaks at 81 minutes after inhalation). From here the THCCOOH is excreted out of the body.

With oral ingestion, the effects are felt much later, (up to 1.5 hours), and can last several hours, but have a much steadier intensity and duration of effects. There are a lot more factors in determining the length of effects with oral ingestion due to the extra steps involved with digestion, and individual differences in liver metabolism, and digestion. Even still, the breakdown follows the same process once reaching blood circulation, and ultimatly the liver. 

How long it takes to metabolize thc infographic

Justin Cooke @JuzzieCooke

The Sunlight Experiment @TheSunlightExp

References:

  1. Cannabis Culture. (2009). Evolution of Trichomes [Photograph]. Retrieved from http://www.cannabisculture.com/content/2009/06/12/inside-trichome
  2. Chang C.Y, Ke D.S, and Chen J.Y. (2009). Essential fatty acids and Human Brain. 18(4):231-41.
  3. Gertsch, J., Pertwee, R. G., & Di Marzo, V. (2010). Phytocannabinoids beyond the Cannabis plant - do they exist? British Journal of Pharmacology, 160(3), 523-529. doi:10.1111/j.1476-5381.2010.00745.x
  4. Greydanus D.E, Hawver E.K, Greydanus M.M, and Merrick J. (2013). Marijuana:current concepts. Frontiers in Public Health. 1. 42.
  5. Russo E. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 163. 1344-1364.
  6. Sharma P, Murthy P, Bharath M.M.S. (2012). Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications. Iran J Psychiatry 2012; 7:4: 149-156