Locks and keys of the endocannabinoid system: Cannabinoids bind to “cannabinoid receptors” in your body and brain.
Think of cannabinoid receptors like little locks, and your body’s cannabinoids fitting naturally into these locks like keys. These locks and keys make your endocannabinoid system, which can influence appetite, pain, inflammation, sleep, stress responses, mood, memory, motivation, reward and more.
There are two main cannabinoid receptors – cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2).
CB1 receptors are mostly found in the brain and impact a number of neurotransmitters.
Q. Wait what’s a neurotransmitter? A. It’s a chemical messenger that allows one neuron (a nerve cell) to talk to another neuron, brain or muscle cell).
The neurotransmitters CB1 receptors act on are:
- GABA, the body’s most important neurotransmitter that helps to calm down activity in the brain, allowing us to relax and sleep. Low GABA can lead to stress and anxiety.
- Glutamate which excites the brain and in normal levels is essential for learning and memory. Too much is negative and can lead to restlessness, anxiety, amplified pain and an inability to focus.
- Dopamine, responsible for making you feel awake and alert, but mostly known for the role it plays in motivation and reward. Nearly every pleasurable experience we enjoy - from achieving a goal, eating a great meal to having sex - involves a dopamine release. Chasing a dopamine high can cause addiction from activities like gambling or shopping. Dysfunction of the dopamine system may contribute to bipolar and schizophrenia.
- Serotonin, which affects how you process your emotions and your overall mood. Interestingly, 95% of your serotonin is found in the gut - it’s released when food enters the small intestine and helps to stimulate contractions to push food through your intestine. When a toxin enters the gut, your body produces more serotonin to push it through more quickly, usually through vomiting or diarrhoea. Low serotonin is associated with constipation. Research shows a relationship between low serotonin binding and and increased incidence of anxiety, OCD, autism and also bipolar disorder. The gut has been called your “second brain” and increasing evidence is linking these disorders to gut health.
CB2 receptors, on the other hand, are mostly found within the immune system and blood cells and aren’t associated with getting high. However, they potentially play an even more interesting role, with CB2 receptor dysfunction associated with almost all disease affecting humans - from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone and skin disease as well as pain and even cancer.
It’s important to note that some CB1 receptors are located outside the brain, and some CB2 receptors can be found within the brain. So, there is some overlap.
There are two different types of cannabinoids that can activate these receptors in your body:
Phytocannabinoids – plant-derived cannabinoids, such as tetrahydrocannabinol (THC) found in marijuana and cannabidiol (CBD) found in hemp.
- Endocannabinoids – cannabinoids produced naturally by our body. There are 5 kinds of cannabinoids that our body produces, anandamide and 2-AG being the most well researched:
- Anandamide is the main endocannabinoid in your body. It can be found in humans, but also many other animals and plants. It binds more-so to CB1 than CB2 receptors and has similar effects to THC - in fact, the name anandamide is based on the Sanskrit word ananda meaning “inner bliss.”
- 2-AG (2-arachidonoylglycerol) also binds to the CB1 and CB2 receptors and is the most abundant endocannabinoid found in the body. It doesn’t have such cool name as anandamide, but it has been shown to play an important role in regulation of appetite, immune system function and pain management. It is also thought that 2-AG may play a role in the inhibition of cancer cell proliferation - but more research is needed there.
- Virodhamine - named from the Sanskrit word virodha, which means opposition, as it does the opposite of anandamide i.e. it partially blocks the CB1 receptor and binds mostly to the CB2 receptor. One study has shown that Virodhamine can relax pulmonary arteries, helping to relieve hypertension.
- NADA (N-arachidonoyl-dopamine) - a recently discovered cannabinoid that binds to the CB1 receptor and has antioxidant and neuroprotective properties.
- 2-AGE (2-arachidonyl glyceryl ether or noladin ether) also acts on both the CB1 and CB2 receptors.
To sum all of this up in practical terms… Low levels of endocannabinoids = disease
There is an increasing amount of research linking a number of illnesses and symptoms to low endocannabinoids levels, including:
Generalized anxiety disorder
Post-traumatic stress disorder (PTSD)
Attention-deficit/hyperactivity disorder (ADHD)
Some researchers are convinced that when your body doesn’t produce enough endocannabinoids you’re more likely to develop these diseases.
This led to terms being coined like "clinical endocannabinoid deficiency" and "endocannabinoid tone" to describe the health of a person's endocannabinoid system and potentially to use as a way to measure overall health as well.
The endocannabinoid system and stress
If there's one thing most of us can agree on, it's that we're all stressed. And whether it’s a small thing like getting stuck in traffic, or major stressors like losing a loved one, we encounter stress in one form or another on a daily basis. Fascinating research has identified that the endocannabinoid system plays a major role in the way our body responds to stress.
This could have major implications for how we diagnose and treat illnesses. Almost every health problem out there—including extremely common ones like anxiety, depression, heart disease, GI issues, asthma, and headaches—can be exacerbated by stress and are likely even caused by it.
So cannabinoids are the keys to our endocannabinoid system’s locks. There are over 120 cannabinoids found in cannabis and other plants, plus 5 known endocannabinoids made naturally by our body. There’s lots more to learn, but we do know that not only can cannabinoids like THC get us high, others like CBD and 2-AG can help to reduce stress and anxiety, regulate serotonin levels in our gut, support our immune system and help us sleep, ultimately equipping us to manage daily stressors better and improve our health.