100% of vertebrates have an endocannabinoid system

We humans are machines. A tightly coordinated biological machine comprised of trillions of cells. Each of these cells is in a constant state of communication with its immediate neighbours as well as with the central controlling system that is the brain.

These communications are tightly regulated and balanced by the body. We are now realising that in disease, this tightly coordinated communication is often compromised and dysregulated in some way. The identification of the cannabis-based cannabinoid or phytocannabinoid, tetrahydrocannabinol (THC) ultimately led to the discovery of the system that is responsible for this delicate balancing act, the Endocannabinoid System (ECS). Since its initial discovery in the late 1900’s, our knowledge of the endocannabinoid system has advanced at a startling pace. We now know the ECS to be involved in almost all diseases. This provides researchers with the unique opportunity to begin reanalysing methods of treating a variety of diseases. This is particularly exciting for conditions for which no treatments currently exist.

The ECS is comprised of 3 elements that provide a feedback loop for all cellular communication, reducing signalling when cells become overstimulated, and increasing signalling when stimulation is needed. Proteins called enzymes are responsible for synthesizing and degrading the internal signalling molecules known as Endocannabinoids. These endocannabinoids are rapidly exchanged between cells where they bind to specific cannabinoid receptors to regulate the strength of cellular communication. The binding endocannabinoids to these receptors triggers a series of further messages that regulates the over all strength of the signal being sent. The proportions of these endocannabinoid molecules, enzymes and receptors is in a state of constant dynamic change, alternating the various proportions of each of the three elements to maintain the overall balance of communications.
Medical professionals are beginning to appreciate the therapeutic potential of manipulating this system to treat disease.

Patients suffering from inflammatory diseases such as Rheumatoid arthritis stand to benefit greatly from the discovery of the ECS. Few treatments currently exist for arthritis and as a result there are roughly 400,000 people in the UK suffering daily with this debilitating condition. As a result, large numbers of arthritis patients have taken to the internet in pursuit of some form of symptom relief. This has led numerous patients to explore the potential of cannabis oils to alleviate their pain. The pain these patients experience stems from the irritation of sensory neurons and damage to the sensory circuitry connected to the body’s  joints (McDougall, 2006). In healthy tissue these nervous cells are only stimulated during injury, but in arthritic joints there is a sustained uncontrolled inflammatory response which leads to painful, hyper-sensitive joints which falsely stimulate pain when performing day to day movements. This joint inflammation is a falsely triggered natural immune response which has misidentified none harmful stimuli. The ECS provides a unique mechanism by which we can manipulate the falsely triggered inflammation and sensory pain. This method offers an exciting potential treatment strategy for thousands of people which has gathered support through the use of animal studies we have identified that the elements of the ECS exhibit a variety of imbalances in inflammatory diseases such as Rheumatoid arthritis. Specifically, these animal studies have observed an increased number of ECS receptors in the tissue of arthritic joints. More specifically, the tissue of arthritic joints contains a higher proportion of Cannabinoid Receptor 1 (CB1) and the cannabinoid receptor 2 (CB2)(Barrie and Manolios, 2017). It is thought that the increase in receptors expression is the body’s natural response to a decrease in the availability of endocannabinoids that would usually bind to these receptors.

The phytocannabinoids found in cannabis oil share unique chemical properties with endocannabinoid that allows them to bind to these cannabinoid receptors within the body. Specifically, THC mimics the chemical effects of the endocannabinoid, Anandamide, which is naturally produced in the body, and usually activates the CB1 receptor.  This binding has a calming effect on the irritated neurons and reduces pain by reducing the firing rate of nerve fibres, inhibiting the heightened pain detection. This increase in cannabinoid receptors, is believed to be the response to a reduction in the overall production of endocannabinoids within the nervous system of joints.The significance of this is that THC and other such phytocannabinoid can be used in a variety of diseases where the ECS exhibits signs of imbalance. This binding of THC to CB1 is what provides this therapeutically in a variety of diseases. Though this may be a generalisation, the effects of cannabinoids depend wholly on the characteristics of each person’s ECS. For instance, the distribution of cannabinoid receptors across the various bodily tissues will vary, and this underlying “abnormality” will vary, case by case, depending specifically on which elements of the ECS are lacking or overabundant. And so for this reason it is imperative that we discuss the ECS in greater detail when discussing medical cannabis. The ECS offers some truly revolutionary therapeutic options to researchers. The unrefined nature of medical cannabis is one of the key reasons it has been so ethically challenging for NHS medical professionals to informedly prescribe cannabis-based therapeutics. Our archaic affirmation that Cannabis had no medical value has meant that we are decades behind in our medical understanding of cannabis medicines.

Ultimately, we may move away from these crude cannabis treatments and use a variety of more streamlined pharmaceutical methods to manage diseases. We already have the capacity to manufacture cannabinoids using bacteria and yeast, yielding cannabinoids at a far more profitable ration than classical farmed methods. These endocannabinoids are currently in the process of being refined to provide more therapeutic accuracy than their natural counterparts. Given the complications and controversies of cannabis currently, one would expect that we shall eventually move away from unrefined cannabis products in medicine. We are years away from receiving refined ECS therapies through the NHS, and asa result we are limiting early treatment access to a significant number of patients across the UK. The reluctance of British medicine to incorporate cannabinoids is driving desperate patients to alleviate their suffering by self-administering these crude ancient methods of cannabinoid therapy. This regularly places patients in a position where they are forced to break the law in order alleviate their suffering. Clearly there is a tremendous space for medical advancement in ECS therapies, this is currently overshadowed by misinformation and stigma surrounding the public perception of Cannabis based medicines. By raising awareness for the endocannabinoid system you may be able to contribute in your own way to the national appreciation of ECS therapies and cannabis based medicines. 

Findings

Resources

Barrie, N. and Manolios, N. (2017) ‘The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease.’, European journal of rheumatology. AVES, 4(3), pp. 210–218. doi: 10.5152/eurjrheum.2017.17025.McDougall, J. J. (2006) ‘Arthritis and Pain. Neurogenic origin of joint pain’, Arthritis Research & Therapy 2006 8:6. BioMed Central, 8(6), p. 220. doi: 10.1186/AR2069.

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