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The Endocannabinoid system and Epilepsy

Updated: Feb 22

The potential of Endocannabinoid system therapies in epilepsy.



The human body is complex system of rapidly communicating cells that work together in synchronicity with other cells throughout the body comprising the body’s various tissue and organs. This constant cellular communication requires a constant and intricate balancing act which we now know to be regulated by the Endocannabinoid System (ECS). Our knowledge of the endocannabinoid system has advanced rapidly since its initial discovery some 50 years ago. The emergence of the ECS has afforded researchers an exciting new therapeutic target which holds a vast array of treatment strategies and gives new hope to patients suffering from diseases for which treatments do not currently exist.


“Many of these oils often contain high concentrations of the psychoactive cannabis constituent tetrahydrocannabinol (THC), raising a great deal of concern amongst medical professionals who fear its long-term effects on brain development.”

In conditions such as epilepsy, there are certain disorders for which existing treatments offer little to no respite from life threatening seizures. In recent years we have seen an emergence of these such patients crudely utilizing cannabis oils therapeutically to alleviate their symptoms. Though these patients, sometimes children, may derive great benefit from these crude methods. Many of these oils often contain high concentrations of the psychoactive cannabis constituent tetrahydrocannabinol (THC), raising a great deal of concern amongst medical professionals who fear its long-term effects on brain development. Such medical professionals raise legitimate concerns but are often perceived to be inhibiting access to a legitimate medicine. In challenging circumstances such as these patients and parents often feel unable to relate to the hesitant medical professionals due to their desperation. This, in many cases, has resulted in patients knowingly breaking the law in order to self-administer these crude treatments. Much heated debate currently surrounds the medical cannabis, with both sides providing legitimate rationale. At the core of this debate, however, is the knowledge that this field of medicine is still in its infancy. Decades of research years have been lost. A direct result of the war on drugs and the misidentification of cannabis as a substance that holds no therapeutic value. This disparity in understanding will rapidly close and as it does, likely provide answers to many of the health concerns raised by healthcare professionals.



What is epilepsy?


One of the most interesting aspects of the ECS is its ability to regulate the neuronal signalling network. In diseases such as epilepsy, the tight regulatory balance of this neural network is often compromised in some way, leading to rapid surges of uncontrolled neural signalling. The effect of this is a neural “storm” that induces severe and sometimes chronic seizing. In some cases, conventional pharmaceutical treatments do exist, often providing much needed relief to vulnerable patients. In the absence of effective treatments however, many patients have, out of desperation, looked to the internet for answers and discovered an online community of patients crudely utilising raw cannabis products with promising results. The hesitation in adopting these treatments is, in part, due to the underlying exposure of the brain to THC. Though some may derive serious benefit, patient responsiveness varies substantially with some treatments exacerbating seizures (Rosenberg et al., 2015). In terms of our understanding of cannabis, the use of raw cannabis oils as a therapy for disease would be comparable to the crude use of opium extracts in the 1940’s. Cannabis treatments are many years from being refined pharmaceuticals, but in their current crude form provide a vital source of early relief to a large population of patients across the globe.


Decoding the Endocannabinoid system


Given our currently questionable understanding of the ECS, it is safe to say that though doctors and medical cannabis advocates both have their legitimate causes for concern. It is true, medical cannabis, in its current form, is not yet fit for the NHS’s high standards. It has however provided a tremendous platform from which the ECS can be discussed and opened up to international investigation. Medical cannabis has already paved the way for ECS based therapies which will one day enable us to sidestep the perceived perils of unrefined medical cannabis. As our technologies develop, we will slowly decode the intricacies of the ECS, enabling us to target elements of the ECS with specific drugs that can precisely manipulate this system therapeutically. Our current knowledge is limited but crude supplementation with systemic cannabis oil treatments, which can still provide life changing results. As the ECS decoding process matures, we will be able to traverse the unwanted side effects of current cannabis-based therapeutics using precise and targeted manipulation of the ECS.



For some years now, work has been underway to translate the anecdotal evidence for cannabis therapies into evidence-based therapies. Explorative studies investigating how the ECS may be altered in the epileptic brain have shown that elements of the ECS may be damaged or under expressed. The CB1 receptor has been repeatedly observed to be deficient in the epileptic human hippocampus (Ludányi et al., 2008). The significance of this is that THC, the most abundant compound in cannabis, targets and activates the CB1receptor. This binding of THC to CB1 initiates this anti-epileptic effect. Though this is a generalisation, the effect depends on the characteristics of the individual’s ECS. The CB1 distribution across the various neuronal tissues will vary, and this underlying “deficiency” will vary, case by case, depending specifically on which types of neurons in the brain are deficient in these cannabinoid receptors. It is becoming clear that this same relationship is true for many diseases, ranging from cancer to arthritis. For this reason, it is imperative that we discuss the ECS in greater detail when debating medical cannabis. Truly, it is the ECS that offers the greatest therapeutic potential.


Cannabis and epilepsy


Cannabis offers relief to so many as it contains phytocannabinoids (such as THC), which mimic the signalling molecules (endocannabinoids) of the ECS. Specifically, THC mimics the effects of the Endocannabinoid, Anandamide, which is naturally produced in the body. Under standard physiological conditions, anandamide binds to and activates the CB1 receptor. It was this relationship led to the initial identification of the ECS in 1964 (Gaoni and Mechoulam, 1964). Though this is just one example of this relationship, there are multiple other cannabinoid receptors with corresponding endocannabinoids that interact with phytocannabinoids in this way.


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. On one hand, cannabis has genuine medical benefits, on the other hand, we have no refined therapies. Our archaic affirmation that cannabis has no medical value has meant that we are decades behind in our medical understanding of cannabis medicines. this may mean that we move away from these crude cannabis treatments and use a variety of more streamlined pharmaceutical methods to manage diseases.

“Our archaic affirmation that cannabis has no medical value has meant that we are decades behind in our medical understanding of cannabis medicines.”

In Conclusion


We already have the capacity to manufacture endocannabinoids. These endocannabinoids are already in the process of being redesigned to improve therapeutic accuracy of cannabis treatments. Given the current complications and controversies of cannabis, one would expect that we shall eventually graduate from the use of medical cannabis products and adopt a new branch of synthetically engineered endocannabinoid therapies. Unfortunately, we are many years away from receiving these refined cannabinoid treatments through the NHS. Our current assessment and treatment of cannabis users is damaging to a significant number of patients across the UK who are desperate to utilise these crude ancient methods of cannabinoid therapy as it is their only hope.


References:

  1. Gaoni, Y. and Mechoulam, R. (1964) ‘Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish’, Journal of the American Chemical Society. American Chemical Society , 86(8), pp. 1646–1647. doi: 10.1021/ja01062a046.

  2. Ludányi, A. et al. (2008) ‘Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus.’, The Journal of neuroscience : the official journal of the Society for Neuroscience. Society for Neuroscience, 28(12), pp. 2976–90. doi: 10.1523/JNEUROSCI.4465-07.2008.

  3. Rosenberg, E. C. et al. (2015) ‘Cannabinoids and Epilepsy’, Neurotherapeutics. Springer US, 12(4), pp. 747–768. doi: 10.1007/s13311-015-0375-5.


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