In this episode we introduce the endocannabinoid system; the part of your body that responds to CBD and THC.
Episode 9 – The Endocannabinoid System
Hi there and welcome to the Hemp Community podcast, my name is dan and on this week’s episode we’re going to be discussing the part of your body that responds to cannabis, namely the endocannabinoid system.
For a little bit of context, The Hemp Community is a social enterprise in Edinburgh Scotland, and we sell a range of CBD products including oils, pastes, gummies and more. We work with a wide range of individuals and families who use CBD for their health. CBD is one of many compounds produced on flowering tops of cannabis plants, including hemp plants. It doesn’t get you high like THC, but CBD is rightly a very popular consumer product and a key ingredient in many cannabis based medicines. The majority of people that I work with are cannabis naïve meaning they have either never used it or have very little experience of cannabis. Some of our customers have used cannabis in the course of their youth, and there are equally as many of our customers who are regular consumers. The vast majority of new customers we receive at the hemp community are people who have never taken a deliberate dose of CBD. Perhaps not surprising is that we get a lot of questions about cannabis and cannabinoids and one of the most common questions we get relates to how CBD works. This question can express itself through different vocabulary, for example people might ask “does CBD work for pain” or “can I use CBD for sleep”. In my view there is something in the phrasing of these questions implies that CBD is a compound that does something to your body, as if it is something new and unrelated that exerts a powerful chemical effect on you. This mode of thinking is useful for pharmaceutical drugs which have spent thousands of hours in a lab being designed for specific indications, but the approach misses the mark when we discuss the relationship between cannabis and its effects. My understanding of how cannabis works focuses not on what cannabis does to your body, but rather what your body does with cannabis, and hopefully by the end of this episode of the podcast you’ll understand why I prefer to approach cannabinoid therapy with a focus on physiology and not pharmacology.
As a quick reminder for those of you are new to the podcast the term “cannabinoid” refers to a group of chemical compounds found throughout nature. Animals, plants and even some fungi produce cannabinoids, but they were first found on the cannabis plant, hence the name. Cannabinoids like CBD and THC come from the cannabis plant, and we can call them phytocannabinoids, where the prefix “phyto” comes for the Greek for “plant”. CBD and THC were first isolated in 1969, and for many years the popular belief in the scientific community was the effects of cannabis, both medical and recreational, were facilitated by these plant compounds acting on our brains through a yet unknown mechanism. Not long after the discovery of cannabinoids, US President Richard Nixon declared War on Drugs, and around the world zero-tolerance anti-drugs policy became the standard, including in the UK in the form of the Misuse of Substances Act 1971. Having just discovered the active ingredients in cannabis, the scientific community found itself unable to continue research into cannabinoids, except under strict conditions. In the UK, research licenses for cannabis are controlled by the Home Office who over the decades have remained aggressively reluctant to look at new evidence.
In the late 80s and early 90s there were a series of developments in neuroscience that confirmed the existence of cannabinoid receptors; sites in the brain that respond to the chemicals expressed on the cannabis plant. Researchers determined that the mammalian brain has 2 cannabinoid receptors, neatly labelled CB1 and CB2. The significance was immediately understood even at this early stage, due to the prevalence of these receptors in the central nervous system and immune system respectively.
With confirmation that the human brain has its own cannabinoid receptors, researchers suspected that the brain might be making its own cannabinoids to service these receptors, and they were right. It turns our cannabis isn’t the only earthling that produces cannabinoids; humans do too! In fact, every animal on the planet that has a spine makes its own cannabinoids; endocannabinoids, the prefix endo is short for endogenous meaning these cannabinoids are made within the body. So not only do we produce our own cannabinoids receptors, we make the cannabinoids to activate them and we also come equipped with enzymes and transporter molecules to break down and relocate the compounds ad hoc. Altogether, these ingredients make up the endocannabinoid system, which is of course the subject of today’s podcast.
The endocannabinoid system is understood to have evolved some billion-odd years ago in a small squidgy marine creature called a “Sea Squirt”; they might look quite alien to us, but we are in fact very distantly related, as are all vertebrate animals. Modern studies of Sea Squirt physiology have identified that their brains, hearts, digestive tracts and reproductive organs are saturated with cannabinoids and receptors. What I find even more interesting, is that the endocannabinoids produced by the sea squirt are the same as in humans; 2AG and Anandamide.
To keep things simple I’m going to summarise that 2AG and Anandamide are your body’s equivalents of CBD and THC. They’re not exactly the same, but today’s podcast is not about the minutiae of cannabinoid chemistry and pharmokinetics. I like the visualise CBD and THC as blue and green molecules, and while the human cannabinoids 2AG and Anandamide might be a slightly different shape, they are the same colour and at sufficient distance we can overlook the differences between them and just watch them dance.
2AG and Anandamide are neurotransmitters; chemicals that your brain uses to regulate all the electrical activity that goes on between your ears. The human brain produces many types of neurotransmitters that work on different receptors to achieve specific ends. One of the things that makes cannabinoids interesting is that they are found almost everywhere and seem to do a little bit of everything. As a matter of fact, the endocannabinoid system plays a regulatory role in the production of many of your other neurotransmitters. For example; about half of your serotonin pathways are managed by endocannabinoids, and ALL of your brain’s dopamine requires endocannabinoid signalling to function. The endocannabinoid receptors are believed to be among the most common in the central nervous system, and they are also found in varying concentrations in multiple tissues in every other physiological system including the digestive tract, reproductive organs, pulmonary & circulatory system and the list goes on.
There are thought to be as many as 5 different types of cannabinoid receptor, but by far the most common and best udnerstood are CB1 and CB2. Generally where you find one type of receptor you will find the other, although the ratio of the receptors varies depending on the tissue; for example CB1 receptors are dominant in the central nervous system, whereas the immune system uses mostly CB2 receptors. Accordingly the cannabinoid transmitters themselves are expressed near the receptors so they can produced on demand.
Understanding that we have a lot of cannabinoid receptors is one thing, but it does beg the question “what are they doing?”; Billions of cannabinoid receptors and a seemingly neverending production line of cannabinoid neurotransmitters; why?
Your brain is constantly sending and receiving electrical impulses, and every individual brain cell oscillates between “on” and “off”. The endocannabinoid system introduces more nuanced control of this signalling, much like a dimmer switch on a lamp; in doing so the cannabinoids becomes the regulator of a plethora of neural activity including many processes that are part of our conscious experience. The sum total of the endocannabinoid system’s function can be summed up in the word homeostasis, which means “balance”.
So lets have some examples; a whistle-stop tour of the endocannabinoid system starting in the brain. As mentioned, almost every tissue of the brain uses cannabinoids for something or other and in fact that the only part of the brain that doesn’t have cannabinoid receptors is the brainstem which itself controls a range of vital function such as breathing and keeping your heart beating. The absence of cannabinoid receptors on the brainstem is why it is considered impossible in practical terms to overdose on cannabis. Outwith the brainstem there are a few interesting cannabinoid hotspots in the brain, such as the hippocampus which regulates memory; your brain is constantly making decisions about which sets of information are to be stored long term, and what details can be forgotten. Imagine if you will, being able to remember every car registration plate you’d ever seen but never being able to remember where you left your keys; the ability to forget is as important as the ability to recall. Cannabinoids are also an important part of the process of memory consolidation, which is one of the reasons why many people with PTSD and mood disorders use cannabis as medicine. Similarly, cannabinoids are important in the regulation of mood, motivation, appetite and sleep, all processes that can struggle to maintain balance when reacting to an unpredictable world. Every time we encounter a change in our internal or external environment, our endocannabinoid systems respond by shaping and guiding our neurophysiological response, and at the end of a long day cannabinoids will even tuck us into bed.
Outside of the brain cannabinoids perform a spectacular array of odd jobs; CB1 receptors in your eyes are used to facilitate the activity of the photo-sensitive retina that allow us to see in colour. CB2 receptors are found on every immune cell throughout the body making sure they maintain a firm but fair approach to fighting infection and regulating inflammation. Cannabinoid receptors are found throughout the tissues in your gut and liver, and with that in mind it comes as no surprise that we see so many people at the hemp community with digestive health issues including IBS and Crohn’s disease. While we’re discussing endocannabinoid physiology in the abdomen, it may be of interest to you that human reproductive organs and in particular female reproductive organs use cannabinoids to maintain their healthy function. It is not a coincidence that for millennia women have used cannabis as a treatment for menstrual discomfort and for managing symptoms of the menopause.
The endocannabinoid system is versatile and pervasive; it does lots of jobs and it does them all over your body and around the clock. For most people, their own cannabinoids are enough and a plant like cannabis is just a curiosity, but for anyone with an unbalanced or depleted endocannabinoid system, cannabis is godsend; a bountiful source of cannabinoids like CBD and THC, which can fill in for the endocannabinoids and then some. When we use cannabis, we are feeding our endocannabinoid systems with nutrients that it can use to continue its important work of keeping us in a healthy state of balanced function.
As with any system of the body, the endocannabinoid system is not perfect and it can malfunction; the concept of clinical endocannabinoid deficiency was first articulated in 2004 by a researcher at a British Pharmaceutical Company who postulated that a range of treatment resistant and apparently idiosyncratic disorders may in fact be connected through a shared dysfunction in the endocannabinoid system. In particular, conditions like IBS, Migraine and Fibromyalgia all share similar bio-chemical and pathophysiological characteristics, and importantly a significant number of patients use cannabis to manage these conditions, and report great success in doing so. The more coincidences you see, the fewer there are.
An endocannabinoid deficiency may be something an individual is born with, but equally it may be acquired in later life. There is also a debate to be had over whether or not endocannabinoid disorders are a cause or symptom of other diseases. For example, in 2007 neuroscience researchers in Italy identified that there are significant differences between the endocannabinoid systems of people with and without Multiple Sclerosis; in particular, brains with MS produce and maintain significantly higher levels of the endocannabinoid Anandamide. My reasoning tells me that this enhanced cannabinoid activity is in response to the conditions of MS and not the other way around. To support my argument I would introduce the story of Jo Cameron, a Scottish Nurse who has a rare genetic defect which means her brain is swimming in anandamide; her endocannabinoid system is missing the enzyme that breaks down anandamide after it has been used and the end result is that Jo doesn’t feel pain or anxiety. She has even given birth without any kind of pain management describing the experience as being “a bit ticklish”. If excess anandamide were causative of MS, Jo Cameron would be a prime candidate, and yet the septuagenarian is a picture of physical and mental health because of an overactive endocannabinoid system.
I find it difficult to imagine a health condition that is not effected by cannabinoid signalling. The endocannabinoid system is found throughout the body and is foundational to human health and well-being. We know as a certainty that every human being has an endocannabinoid system, and we know that the cannabis plant is capable of producing a stunning and prolific variety of safe cannabinoids that our bodies can utilise. There is no doubt that cannabis has been, and continues to be used by millions of humans the world over to manage a range of health conditions including minor ailments, life changing diseases and everything in between. The prohibition of cannabis is based on decades of bad faith and prejudice, but despite international governmental conspiracies to quiet research into the cannabis plant, the answer was inside us all along.
One of my favourite characteristics of the endocannabinoid system is its discerning nature, and by that I mean the way in which it is able to detect and appreciate good cannabinoids, whist rejecting bad cannabinoids. By good and bad, I mean natural cannabinoids versus synthetic cannabinoids. We’ve not gone into a lot of detail on synthetic cannabinoids in the podcast series yet, but I’ll quickly summarise. Following the prohibition of cannabis, pharmaceutical companies made their own cannabinoids but as a group, synthetic cannabinoids have a questionable safety record and are unpleasant to consume. Loopholes in the law allowed synthetic cannabinoids to flood the consumer market in the form of legal highs in the early years of the 21st century, leading to an epidemic of harm, particularly in vulnerable groups. The human endocannabinoid system does not react favourably to synthetic cannabinoids, and the disruptions in endocannabinoid function can be highly distressing and even life-threatening. Thankfully natural, plant based cannabis products are growing in popularity as enthusiasm for prohibition wanes.
Hopefully you have followed the podcast so far and you will be aware that there are thousands of varieties of cannabis, some high in THC, some high in CBD and many balances in between. You will also be aware that cannabis can be prepared and consumed in as many ways as the human imagination will allow. There are tens of thousands of research papers investigating the particular qualities and utility of individual cannabinoids on various symptoms and diseases, and research is ongoing trying to join the dots and identify which balance of which cannabinoids will give individuals the best health outcomes. It is crucial that we have as much evidence as possible so that decision makers are well informed, but I think that when it comes to the real-world interaction between plant and patient much of the current research is of little use. For example, studies that seek to investigate cannabis’ efficacy as a treatment for pain often show the plant to be wonting in effect, and yet pain management remains one of if not the most common reason why people use medical cannabis. If you find this counter-intuitive you’re not the only one; the solution to this problem lies not in the pharmacology of the cannabinoids, but within the physiology of the person taking the cannabinoids; simply put there is more to suffering than just physical pain. Cannabis works as a pain killer by redirecting attention way from the source, and then by gently scrubbing the brain’s memory of the pain in such a was as to minimise it’s impact. Cannabinoids can also have an effect on pain by reducing inflammation, or inducing sleep, but whatever we use cannabis for it is our own bodies that do the work; cannabinoids are merely the tools that the endocannabinoid system uses.
The implications of the endocannabinoid system are huge, and may even qualify as a paradigm shift in western medicine. There are innumerable doses of pharmaceutical medications that could be replaced by non-toxic, non-addicting and generally pleasant cannabis. Every ward in the hospital could benefit from an cannabinoid therapist; whether its pain management, or reproductive health or psychiatric illness, every patient faces compromises in their quality of life when they are in unwell. Cannabis may not work for every one of these patients, but given cannabis medicines record thus far these patients have nothing to lose and perhaps everything to gain.
Every endocannabinoid system is different; my receptors are set up different to yours and yours are different to the next person’s and so on. Different cannabinoid preparations will yield varying results depending on how they are administered and also to whom they are given. This is why consumers of cannabis, be they medical patients or so-called recreational users, should have choices regarding the types of products that they use, because subjective experience is so varied in the cannabis world. Some people will need more THC, some people may not need as much, but my intuition says and my experience thus far has taught me that you can’t always predict what is going to work for someone walking in the door. Like I have said for many years now; CBD is not just a product, it is a process.
There are of course some general rules that hold for most people, and while individual differences are commonplace in cannabinoid therapy I suggest the following guidelines for anyone interested in using cannabis for their health. First of all start low and go slow; your endocannabinoid system is incredible and can do amazing things with phytocannabinoids, but it will probably want a little practice first. Start with a small dose and use routinely, and gradually increase until you find what works best. The second important tip is to be consistent; time is the secret ingredient, and particularly when using CBD progress is best measured in weeks and months. My third suggestion is somewhat antithetical to the preceding tip and that is don’t be afraid to mix it up every once in a while! Your endocannabinoid system likes routine and consistency it also likes a little change now and then so by all means feel free to experiment with different products and approaches and give your endocannabinoid system something to chew on.
When we consciously set out to look after our endocannabinoid systems, an incredible thing happens; it starts to look after us in return. This is the big secret behind cannabis; it doesn’t do the work, you do. You are an active participant in the exchange between cannabis and your endocannabinoid system, and by focusing on the underlying physiology that facilitates the effects of cannabis you can get a better understanding of both the plant and the people that use it.
In future episodes I hope to go into more detail about the endocannabinoid system, but hopefully you’ve learned something today and as always if you have any questions regarding CBD, THC cannabis and health, then please get in touch via our website, social media or email us at Podcast@hempcommunity.scot