Globally, understanding and acceptance of the important role of cannabis is gradually improving – a fact that is long overdue, considering our long history with the plant. A growing number of patients are accessing life-changing cannabis medications, and casual users are slowly shedding the stereotypes and stigma associated with its recreational use. However, despite this steady trend of liberalisation, our understanding of how cannabis actually interacts with the body is still relatively underdeveloped. What we do know is that the endocannabinoid system (ECS) plays a pivotal role.
But what is the endocannabinoid system? Let’s find out.
What is the endocannabinoid system?
The ECS is a receptor system in the bodies of humans, as well as many other animals. It is made up of receptors, neurotransmitters and enzymes that are expressed primarily throughout the immune system and the central nervous system. Research into the ECS has found that it likely plays an important role in a large number of physiological and cognitive processes, including sleep, mood, and pain signalling. It is often credited with maintaining the body’s homeostasis. These findings have prompted further research to learn how the ECS could be an effective therapeutic target for the treatment of various health conditions.
There are two known receptors in the ECS – these are aptly named ‘cannabinoid receptor 1’ (CB1) and ‘cannabinoid receptor 2’ (CB2). The neurotransmitters that interact with these receptors are called endogenous cannabinoids, or ‘endocannabinoids’; however, these are not the only compounds that have been found to interact with the cannabinoid receptors.
The two most well-known of the endocannabinoids are 2-AG and anandamide – two compounds that have similar chemical structures to compounds found in the cannabis plant. These compounds are known as phytocannabinoids, or simply ‘cannabinoids. Interactions between cannabinoids (endo and phyto) are thought to trigger a number of responses throughout the body and are largely responsible for the diverse effects of cannabis.
Cannabinoids and the ECS
The discovery of the active compounds in cannabis – particularly cannabidiol (CBD) in 1940 and delta-9 tetrahydrocannabinol (THC) in 1964 – were largely influential in the discovery of the endocannabinoid system. Nonetheless, it wasn’t until 1988 (almost half a decade after the discovery of CBD!) that scientists proved the existence of cannabinoid receptors in mammals. Then began the quest to discover whether the mammalian body also produces an agonist of these receptors.
Eventually, researchers Raphael Mechoulam – who was also behind the 1964 isolation of THC – and Bill Devane isolated a candidate from a pig brain. In 1992, this compound was confirmed to be a partial agonist of the CB1 receptor; it was named ‘anandamide’, taken from the Sanskrit word ‘ananda’ meaning ‘bliss’. Shortly afterwards, another endocannabinoid was discovered – 2-Arachidonoylglycerol (2-AG). These two compounds remain the most researched endocannabinoids.
Phytocannabinoids
For many decades, interest in THC’s psychoactive effects meant that it remained the most researched phytocannabinoid, despite the ongoing discovery of new compounds in the cannabis plant. Soon, evidence was collected to suggest exactly how THC might interact with the endocannabinoid system. THC is primarily a CB1 receptor agonist, however, it can also bind to CB2 receptors. It is partly through these interactions that THC instils its infamous “high”. In contrast, CBD does not bind directly with cannabinoid receptors’ active site. Instead, it is believed that CBD inhibits endocannabinoid signalling by binding to the CB1 receptors allosteric site (a site other than the active site). This may lead to heightened levels of endocannabinoids such as anandamide.
But far from solely triggering a serious case of the munchies, interactions between cannabinoids and the endocannabinoid system have been found to have some impressive therapeutic effects.
The ECS and CBD
The use of CBD is now widespread amongst the general public. Estimates vary, but it is thought that between 1.3 and 6 million people in the UK turn to CBD oils, gummies, drinks or other delivery methods to get a dose of this popular cannabinoid.
As we’ve learnt, CBD can increase levels of the body’s own cannabinoid anandamide. High levels of anandamide allow your homeostatic mechanisms to work effectively by allowing your body to respond quickly and efficiently to imbalances in your body. When you are feeling run down, stressed or unwell your body often has a low level of anandamide and is less able to effectively recover from the stress you are under.
When our body is put under any kind of stress from anxiety, tiredness, disease or chronic condition it produces anandamide to support your body’s responses. However, it is usually produced just for the immediate situation which means that it has a short life. Once it has completed its task it’s broken down by enzymes into its parts.
If CBD is present, it acts to prevent these enzymes from starting the breakdown of anandamide. Once the enzymes stop working, the level of anandamide builds up. Higher levels of anandamide allow your body to improve its well-being. CBD gives your body the tools it needs to provide its own support.
The ECS and medical cannabis
Cannabis has been consumed medicinally for thousands of years by many civilisations around the world. Yet, before the discovery of the endocannabinoid system, it remained unclear exactly how the plant is able to have such an incredible impact. Furthermore, a primary focus on the psychoactive effects of the plant left the therapeutic potential of cannabinoids under-explored until relatively recently. Nonetheless, we now know that cannabinoids, from CBD and THC and beyond, may have a significant role to play in the treatment of many conditions.
So, let’s take a look at some of the evidence for how cannabinoids, and their interactions with the endocannabinoid system, could benefit our health.
Pain Relief
Today, chronic pain is the most commonly reported reason for medical cannabis use globally. This shouldn’t be surprising, given the plant’s long history as a natural analgesic. This potential benefit of cannabis may lie with the ECS’s role in regulating pain signalling; however, despite an abundance of anecdotal evidence from patients who report having benefitted from the potential pain-relieving effects of cannabis, clinical evidence is still scarce.
A 2016 study on the long-term effects of cannabis on pain and related functioning found that the treatment was associated with improvements in both areas, as well as a reduction in opioid results. Other studies have demonstrated similar findings and real-world evidence is adding to the evidence base to support the use of medical cannabis in this setting. To learn more about medical cannabis for chronic pain, take a look at ‘Medical cannabis and chronic pain – everything you need to know’.
Epilepsy
Medical cannabis has been found to be effective at reducing seizure severity and frequency in some treatment-resistant forms of epilepsy. This anti-convulsant potential, which was highlighted by the campaigns of families in the UK, played a significant role in the legalisation of medical cannabis in 2018.
It is not fully understood how cannabis works to control epileptic seizures; however, its efficacy has been demonstrated in a number of clinical trials and real-world studies. Furthermore, while some patients may benefit from isolated CBD, others find that whole-plant extracts are more effective. To learn more about medical cannabis for epilepsy, take a look at ‘Can medical cannabis be prescribed for epilepsy in the UK?’.
Anxiety
Anxiety disorders are the most common mental health condition, affecting an estimated 4% of the global population – a figure that has been on the rise in recent years. Many people who suffer from anxiety favour natural remedies, making cannabis a popular option. In recent years, in particular, the rising popularity of CBD saw the number of people utilising cannabis to relieve their anxiety skyrocketing. According to a 2021 survey of CBD users in the UK, anxiety was the top reason for using CBD products.
Since the legalisation of medical cannabis in the UK in 2018, medical cannabis can now also be prescribed for anxiety disorders. To learn more about medical cannabis for anxiety, read ‘Can I get a medical cannabis prescription for anxiety in the UK?’.
Other conditions for which medical cannabis may be helpful include multiple sclerosis, depression, obsessive-compulsive disorder, Parkinson’s disease, insomnia, PTSD and more. For more information on medical cannabis prescriptions in the UK, take a look at the comprehensive leafie guide.
