BEHIND THE SCIENCE

THE ENDOCANNABINOID SYSTEM: PART I 

Cannabis is a very old plant that has been used for thousands of years. Its ability to influence the mind has been known for a long time, but due to a lack of knowledge and technology, research and attempts to understand how cannabis works have been very slow. The first breakthrough came in 1964 when scientist R. Mechoulam and his team discovered and then chemically produced one of the phytocannabinoids in cannabis, THC. Subsequent research has also led to the discovery of the receptors with which phytocannabinoids interact and it was observed that our bodies produce cannabinoid compounds themselves. This led to the discovery of the endocannabinoid system, named after cannabis (‘endo’ is short for ‘endogenous’, which means produced within us, and ‘cannabinoids’ refers to cannabis) (Mechoulam and Parker, 2013).

BEHIND THE SCIENCE

THE ENDOCANNABINOID SYSTEM: PART I 

Cannabis is a very old plant that has been used for thousands of years. Its ability to influence the mind has been known for a long time, but due to a lack of knowledge and technology, research and attempts to understand how cannabis works have been very slow. The first breakthrough came in 1964 when scientist R. Mechoulam and his team discovered and then chemically produced one of the phytocannabinoids in cannabis, THC. Subsequent research has also led to the discovery of the receptors with which phytocannabinoids interact and it was observed that our bodies produce cannabinoid compounds themselves. This led to the discovery of the endocannabinoid system, named after cannabis (‘endo’ is short for ‘endogenous’, which means produced within us, and ‘cannabinoids’ refers to cannabis) (Mechoulam and Parker, 2013).

What is the endocannabinoid system?

The endocannabinoid system is a signalling system that is involved in homeostasis – the maintenance of steady-state conditions in the body. The endocannabinoid system consists of 3 main components:

  • Endocannabinoids, 
  • Receptors, 
  • Enzymes (Klumpers and Thacker, 2019).

As mentioned above, endocannabinoids are produced by our body from fatty acids. Endocannabinoids are chemical compounds that bind to receptors and trigger or block further actions. The earliest discovered and most studied compounds are N-arachidonoyl-ethanolamine (abbreviated AEA or anandamide) and 2-arachidonoyl glycerol (abbreviated 2-AG) (Zou and Kumar, 2018).

Receptors are the site that receives a chemical signal, which causes the corresponding effect. Cannabinoid receptors belong to the so-called G-protein family (abbreviated as GPCRs) and 2 cannabinoid receptors have been discovered – CB1 and CB2. CB1 receptors are mainly found in the brain and have been with us since the beginning of life when we were still in the embryonic stage. CB2 receptors, on the other hand, are much more widely spread, being found in the immune and circulatory systems and the central nervous system (Mechoulam and Parker, 2013; Pacher et al., 2006).

Enzymes are proteins that are responsible for releasing and destroying endocannabinoids once they have performed their function. Enzymes control the level of endocannabinoids as needed, maintaining a balance between production and degradation (Zou and Kumar, 2018).

The simplest mechanism to explain the action of endocannabinoids is the metaphor of a key and a lock.  Endocannabinoids bind to receptors and this binding initiates a response. Accordingly, the endocannabinoids act as the key and the receptors as the lock, and once the key reaches the lock, the next event occurs. 

Why do we need an endocannabinoid system?

We mentioned that endocannabinoids are involved in homeostasis, but what does that mean? Homeostasis, translated from Greek, means ‘similar state’. Homeostasis refers to the complex regulatory processes in the body that maintain constant internal environmental conditions. For example, in a healthy adult, blood glucose levels can fluctuate between 3.3 and 5.5 mmol/l and should always remain so. After a meal, glucose levels rise, insulin is released and other biological processes take place to bring glucose back to ‘normal’ levels. Similarly, when glucose levels fall below ‘normal’, glycogen (the glucose stores in the liver and muscles) is broken down into glucose, thus keeping blood glucose levels steady. Our body systems such as the digestive, cardiovascular and circulatory systems need to regulate and maintain the right conditions for optimal functioning. Since homeostasis involves our entire body, it is natural that the endocannabinoid system is involved in many biological processes including digestion, immunity and inflammation, motor regulation, brain function and others (Pagotto et al., 2006).

Why do we need an endocannabinoid system?

We mentioned that endocannabinoids are involved in homeostasis, but what does that mean? Homeostasis, translated from Greek, means ‘similar state’. Homeostasis refers to the complex regulatory processes in the body that maintain constant internal environmental conditions. For example, in a healthy adult, blood glucose levels can fluctuate between 3.3 and 5.5 mmol/l and should always remain so. After a meal, glucose levels rise, insulin is released and other biological processes take place to bring glucose back to ‘normal’ levels. Similarly, when glucose levels fall below ‘normal’, glycogen (the glucose stores in the liver and muscles) is broken down into glucose, thus keeping blood glucose levels steady. Our body systems such as the digestive, cardiovascular and circulatory systems need to regulate and maintain the right conditions for optimal functioning. Since homeostasis involves our entire body, it is natural that the endocannabinoid system is involved in many biological processes including digestion, immunity and inflammation, motor regulation, brain function and others (Pagotto et al., 2006).

Read about the working principle of the endocannabinoid system and how cannabis interacts with it

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References

Klumpers, L.E. and Thacker, D.L. 2019. A brief background on cannabis: From plant to medical indications. Journal of AOAC International. 102(2), pp.412–420. 

Mechoulam, R. and Parker, L.A. 2013. The endocannabinoid system and the brain. Annual Review of Psychology. 64(1), pp.21–47. 

Pacher, P., Bátkai, S. and Kunos, G. 2006. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews. 58(3), pp.389–462. 

Pagotto, U., Marsicano, G., Cota, D., Lutz, B. and Pasquali, R. 2006. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocrine Reviews. 27(1), pp.73–100. 

Zou, S. and Kumar, U. 2018. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International Journal of Molecular Sciences. 19(3), article no: 833 [no pagination].