Cannabis

CB1 and CB2 – The Hidden Health Guardians

The CB1, and CB2 receptors, and the endocannabinoid system are three of the greatest biological discoveries of the 20th century. Science has discovered that nearly all animal and insect species on Earth have an endocannabinoid system. These species – including humans – also produce and modulate their own endocannabinoids which govern organ function, immune function, cognition, digestion, sexual function and much more.

A great number of organisms on the planet produce cannabinoids, but not all can directly benefit from them as they seem to lack their own endocannabinoid systems. One such organism that lacks the endocannabinoid system that has been found to produce over 113 cannabinoids without the ability to directly benefit from them is the hemp/marijuana plant. 

Science has yet to discover why this may be, but a likely theory is that cannabis and humans have such a long history, that symbiosis may be the reason. If two organisms can benefit from each other – in this case cannabis provides cannabinoids and humans in turn cultivate cannabis which in turn helps the plants survive and reproduce – this could well be the reason for cannabis producing so many cannabinoids that it itself cannot benefit from directly.

How CB1 and CB2 were discovered is a bit of a backwards accident which occurred while scientists began trying to isolate why weed gets us high. 

The discovery of the endocannabinoid system, CB1, and CB2 receptors, began in the late 1960s at the Weizmann Institute in Israel. In 1969 scientists Raphael Mechoulam and Yechiel Gaoni first isolated the psychoactive cannabinoid THC, finally having found the first major clue towards the psychoactive properties of marijuana. In discovering THC, Mechoulam and Yechiel’s names entered the history books for opening the door to the beginnings of understanding cannabis, not just as a psychoactive plant but what would later be hypothesised to be a symbiotic partner of humanity. 

The next major discovery of the relationship between cannabinoids and humans next came in 1990 with the discovery of the CB1 receptor, followed by the discovery of the CB2 receptor in 1993, followed then by the discovery of the endocannabinoid system. A bit of a backwards progression to be sure. 

So what do CB1 and CB2 receptors do, exactly? Let’s go over each one separately. There is much more information on each of them than is presented, but for the sake of simply understanding the basics of each one, only brief overviews will be outlined.

 

CB1 Brief Overview

CB1 receptors are one of the oldest systems known to biology and are present in species as old as elephant sharks that have not changed evolutionarily in over 100 million years. CB1 receptors are highly concentrated in the central nervous system throughout the brain, and are also spread out across junctures of the peripheral nervous system. The primary function of CB1 is to act as a sort of input control valve – a volume dial if you will – on the inputs and outputs of the central nervous system which in turn governs behaviour as well as other vital centralised functions. 

How does CB1 get affected when we introduce outside cannabinoids from something like cannabis intake? 

When we smoke, ingest, or vape weed and start to get high, what we’re experiencing is the change in volume on the dial of the central nervous system as THC begins to act upon our CB1 receptors – modulating the flow of enzymes into the receptors. Through this interaction, different things in the body start to happen as the nervous system modulates. Some of the known effects are: a change in pain response, a change in glucose uptake, hunger response, reduction in gut permeability, and even reduction in core organ spasms such as ones prevalent in individuals with crohn’s disease. 

Interestingly, CB1’s effect on blood sugar metabolism, glucose uptake, and appetite regulation is sparking additional studies into why cannabis users tend to have lower BMI in contrast to non-cannabis users with similar diets. What’s strange about this is CB1 seems to play a role in increasing rather than decreasing lipid storage – yes, you read that correctly.

Research into CB1 is still in it’s very early stages with many decades of discovery ahead. One thing that is known for certain is how central it is to the bio-functions of nearly all vertebrate species on the planet. 

A great example of this is if a bird is given a CB1 moulation or blocking treatment, it changes its song pattern. Meaning – for better or worse – the expression of it’s natural and essential instinctual behaviours can be temporarily altered by modulating or blocking the CB1 receptor, because doing so changes endocannabinoid expression postsynaptically, which then changes behaviour.   

 

CB2 Brief Overview 

CB2 has even more limited data available to science than CB1 as it has not been studied in as much detail due to it being a secondary system that is thought to have evolved as a mutation to CB1. Although it can be found in some basic organisms, it’s mostly found in animals with more complex nervous systems like sharks and mammals.

The primary function of CB2 receptors – from the still limited data that are available – appears to be the role of cytokine control and immune signaling response. Unlike the CB1 receptor, CB2 is believed to be affected by the THC cannabinoid (although some speculations to this may still yet be discovered), but rather seems to be largely influenced by the CBD cannabinoid. Although only a theory, the mutation of CB1 into CB2 may have allowed the evolution of more complex organisms like humans by splitting the load of the nervous system over two receptors sites with specialised functions CB1 for cognition and central nervous system functions, and CB2 for immune and inflammatory responses functions. 

The splitting of these two systems at the synaptic level could lead to further research into how CB2 dysfunctions could be the root causes of chronic inflammatory diseases, or maybe even all diseases. As with CB1, many decades of research into this theory needs to be done to have a better picture of how these synaptic receptors function.

What is known is that CB2 appears to play a major role in immune signaling to fight diseases, gut inflammation conditions such as IBS, bacterial/viral infections, cancers, and inflammatory brain diseases such as epilepsy and autism. Which could help explain further the link to CBD and its role in treating seizures.

 

Summary

Although many years of research lie ahead to further decode the mysteries of endocannabinoids, CB1 and CB2 receptors and their various functions, the promise of the potential discoveries could one day reshape the landscape of modern medicines and help bring back the ancestral beliefs that plant medicines such as cannabis play a legitimate role in medicine in the same way modern pharmaceuticals do. 

As important as modern medicines are, there needs to be an ongoing discussion about incorporating ancient medicines that have already proven their value, as we would likely not be where we are today without them.

 

References and Citations

Steve Ottersberg – Physiological Basis of the Endocannabinoid System and Phytocannabinoids – AHS19, Ancestry Foundation, 2019 https://www.youtube.com/watch?v=0fzy93F2das

Chopra A. N-[(1s)-1-[4-[[4-methoxy-2-[(4-[11C]methoxyphenyl)sulfonyl]-phenyl]sulfonyl]phenyl]ethyl]methanesulfonamide. 2010 May 12 [updated 2010 Jun 3]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. PMID: 20642014.

https://pubmed.ncbi.nlm.nih.gov/20642014/

Leung K. 2,2,3,3-Tetramethylcyclopropanecarboxylic acid [3-(2-[11C]methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide. 2010 Dec 6 [updated 2011 Jan 27]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. PMID: 21290620.

https://pubmed.ncbi.nlm.nih.gov/20945557/

Hércules Rezende Freitas, Alinny Rosendo Isaac, Renato Malcher-Lopes, Bruno Lourenço Diaz, Isis Hara Trevenzoli & Ricardo Augusto De Melo Reis (2018) Polyunsaturated fatty acids and endocannabinoids in health and disease, Nutritional Neuroscience, 21:10, 695-714, DOI: 10.1080/1028415X.2017.1347373

https://www.tandfonline.com/doi/abs/10.1080/1028415X.2017.1347373?journalCode=ynns20

Leung K, Donohue S. (3R,5R)-5-(3-[18F]Fluoromethoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one. 2010 Aug 6 [updated 2010 Oct 7]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. PMID: 20945557.https://pubmed.ncbi.nlm.nih.gov/21290620/

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