Effects of Cannabinoids on Metabolic Enzymes

Cannabinoids contained in cannabis impact the bodys endocannabinoid system, producing the characteristic effects of using cannabis, or cannabis containing products.

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Their binding to receptors within the endocannabinoid system is considered to be the main underlying mechanism dictating the characteristic effects of the cannabinoids, such as THC and CBD, however, they also impact the metabolic enzymes whose role it is to break down endocannabinoids after they have served their purpose.

The role of metabolic enzymes in the endocannabinoid system

Metabolic enzymes are a certain class of enzymes that regulate the metabolic pathways involved in homeostasis. They are of particular research interest because they have been shown to be useful targets for drugs treating metabolic diseases and illnesses like diabetes, cardiovascular diseases, obesity, and more.

Within the endocannabinoid system, metabolic enzymes serve to break down the endocannabinoids after they are used.

In a normally functioning endocannabinoid system, metabolic enzymes are deployed to remove the endocannabinoids when they are no longer serving a purpose.

FAAH is one of the major metabolic enzymes, it downgrades anandamide, MAGL is another common metabolic enzyme, and it works to break down 2-AG.

THC, CBD, and FAAH

When smoking cannabis, a high” is induced in the brain of the user because of delta-9-tetrahydrocannabinol, also known as THC, binding to the CB1 receptor in the endocannabinoid system.

THC is a cannabinoid that is introduced into the body through smoking cannabis and consuming cannabis products. It activates the bodys endocannabinoid system in a similar way to how the bodys naturally produced cannabinoids trigger it, through attaching to the various receptors around the body.

THC is known to attach the same receptor as the endocannabinoid known as anandamide, which is the Sanskrit word for bliss - used to describe the calming and pleasant feelings it induces.

When THC attaches to the same receptor, it has the effect of creating a high, however, anandamide does not have the same effect.

This is because anandamide is broken down by the metabolic enzyme FAAH, which means once its done its job it is removed from the system, preventing it from maintaining its blissful” effects. THC on the other hand effects FAAH differently.

In fact, THC does not allow FAAH to break in down in the way it does with anandamide, allowing it to remain in the system and accumulate a much greater effect.

Conversely, the other major component of cannabis, CBD, or cannabidiol, works differently on FAAH. It prevents the enzyme from breaking down anandamide in the brain, allowing it to have more of an impact.

This preventative action on the FAAH enzyme, therefore, results in some of the therapeutic characteristics of cannabis use, such as in reducing anxiety.

However, this discrepancy between the impact of THC and CBD on FAAH is important to note when considering therapeutic interventions, because THC does not induce these therapeutic characteristics. For this reason, many CBD focused products have emerged in recent years to try and capitalize on this effect, without the undesirable effects of THC.

Because of this known function of the cannabinoid CBD on FAAH, it has become a focus of research developing cannabinoid products for therapeutic use.

Many CBD-based products are now available on the market, both via prescription, and for general consumer use, that advertise their use in areas such as anxiety relief and pain relief, as well as being considered effective acne treatments, and are even being considered as potential alternative treatments for illnesses such as cancer, epilepsy, and neurodegenerative disorders such as Alzheimers disease, multiple sclerosis, Parkinsons disease, and stroke.

THC and 2-AG

Less is known about the effects of THC on the endocannabinoid systems other main metabolic enzyme, 2-AG.

However, studies have shown this metabolic enzyme to be expressed in greater quantities within the brain, which has led to suggestions that it may be involved in mechanisms regulating the reward response.

It has also been suggested that THC is able to hijack the normal function of 2-AG. While 2-AG is associated with many functions, such as in mediating the immune functions in the body, and triggering the transportation of immune cells to affected areas to promote healing, some scientists believe that in hijacking the normal function of 2-AG THC may be able to produce its euphoric effects.

However, it is thought that THCs effects on both FAAH and 2-AG are likely to combine to result in THCs sometimes euphoric effects.

Currently, there is a need for more research into the effects of cannabinoids on metabolic enzymes to establish the underlying mechanisms of how substances like THC and CBD impact the body. Once these are determined, researchers will be better positioned to develop new therapeutic treatments that exploit these mechanisms.

Sources:

  • Basavarajappa, B. (2007). Critical Enzymes Involved in Endocannabinoid Metabolism. Protein & Peptide Letters, 14(3), pp.237-246. https://www.ncbi.nlm.nih.gov/pubmed/17346227
  • De Petrocellis, L., Ligresti, A., Moriello, A., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. and Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid-enrichedCannabisextracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology, 163(7), pp.1479-1494. https://www.ncbi.nlm.nih.gov/pubmed/21175579
  • Hryhorowicz, S., Walczak, M., Zakerska-Banaszak, O., Słomski, R. and Skrzypczak-Zielińska, M. (2017). Pharmacogenetics of Cannabinoids. European Journal of Drug Metabolism and Pharmacokinetics, 43(1), pp.1-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794848/

Further Reading

Last Updated: Mar 18, 2020

Sarah Moore

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Sarah Moore

After studying Psychology and then Neuroscience, Sarah quickly found her enjoyment for researching and writing research papers; turning to a passion to connect ideas with people through writing.

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