Can genetics explain why I don’t feel ‘chilled’ even when I’m relaxing?
by Nicqui Grant, RD(SA), IFNCP
Your Body’s Internal Conductor: Understanding the Endocannabinoid System and Genetics
Imagine your body as a vast symphony orchestra, with countless instruments playing in harmony. Now imagine there's a conductor silently guiding every section, adjusting tempo, and responding to shifts in the environment. That conductor is your Endocannabinoid System (ECS), and it plays a key role in keeping your body and mind in balance.
What Is the Endocannabinoid System?
The ECS is a complex cell-signaling system present throughout the body, including the brain, organs, tissues, and immune system. It was only discovered in the 1990s, but scientists now know it's critical in regulating functions like mood, memory, sleep, pain, appetite, and even inflammation.
Think of it as your body’s internal regulator. When something changes, whether it's external (like stress) or internal (like inflammation), the ECS kicks in to help your body respond and return to balance. This constant process of maintaining internal stability is known as homeostasis.
ECS in Action: A Familiar Example
Let’s consider the classic “fight or flight” response. If you hear a loud bang or feel threatened, your amygdala (a part of your brain) quickly sends out alarm signals. Your body responds by producing adrenaline, which primes your muscles, speeds up your heart rate, and prepares you to react.
That adrenaline acts like a key, and your body’s receptors are the locks it fits into. The ECS works in a similar way using its own set of chemical messengers and receptors.
Meet Your Endocannabinoids
Your body naturally produces molecules called endocannabinoids the most well-known being anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These are made on demand (not stored) in the brain and other tissues whenever the body needs them like when you're under stress, in pain, or need to calm down.
Anandamide gets its name from the Sanskrit word ananda, meaning “bliss.” It’s even found in small amounts in chocolate!
These molecules interact with two main types of receptors:
- CB1 receptors, mostly found in the brain and nervous system.
- CB2 receptors, more common in the immune system and inflammation-related pathways.
When endocannabinoids bind to these receptors, they help reduce pain, regulate mood, manage memory, and modulate inflammation.
The ECS and the Brain
In the brain, the ECS is crucial for development. It helps form and prune synapses, which are the connections between brain cells, and supports the creation of new brain cells. It also modulates neurotransmitters, helping your brain balance excitatory and inhibitory signals.
It’s especially important for learning and memory. For example, endocannabinoids are released in response to stressful events. The more often the stress happens, the more efficient your ECS becomes at dampening that stress. In other words, your ECS learns from experience.
They also help filter traumatic memories, reducing the likelihood of forming emotionally harmful associations from overwhelming situations.
Enter Cannabis: THC and CBD
So where does cannabis come into the picture?
Cannabis contains compounds called cannabinoids, the most famous being THC and CBD. THC is a chemical cousin of your body’s endocannabinoids, it can bind to the same CB1 receptors, mimicking natural responses.
However, unlike your own carefully timed and targeted endocannabinoids, THC floods the system all at once. This can disrupt the delicate balance the ECS maintains. Over time, the body compensates by producing fewer receptors and fewer endocannabinoids, leading to tolerance. That’s why frequent users often need more cannabis to get the same effect and why long-term use can impair memory, reduce motivation, and increase the risk of mental health issues in vulnerable individuals.
Genetics Matter Too
Not everyone responds to cannabis in the same way and that’s where genetics come in. Some people have variations (called SNPs) in genes related to the ECS that can affect their vulnerability to cannabis' effects.
For example:
- COMT gene: This gene helps regulate dopamine, the brain’s “reward” chemical. Certain COMT variants break down dopamine more quickly or slowly. Cannabis can boost the effects of dopamine in the brain, and in some people, especially with high doses, this may increase the risk of experiencing things like confusion, paranoia, or even psychosis.
- AKT1 gene: This gene also affects dopamine signaling. Studies show that people with the C-allele variant of AKT1 may be more likely to experience temporary psychotic symptoms (like paranoia or hallucinations) after using cannabis. The risk is especially significant in regular users or those who start using cannabis at a young age. People with this gene who don’t use cannabis generally aren’t at increased risk of psychosis suggesting it’s the interaction between genes and cannabis that matters.
- FAAH gene: Impacts the enzyme that breaks down anandamide (your natural “bliss” molecule). People with a FAAH variant that reduces enzyme activity tend to have higher natural levels of anandamide, which may make them more emotionally resilient but, it also means they may be more sensitive to THC or more prone to addiction. Since FAAH plays a key role in regulating reward and stress, its variants can influence how intensely you feel cannabis's effects.
- EPHX1 gene: This gene plays a regulatory role in the ECS, though it’s not as directly linked to cannabis as the others. EPHX1 affects how the brain responds to inflammation and oxidative stress both of which are influenced by endocannabinoids. Researchers believe EPHX1 may help determine how well your brain copes with the long-term effects of cannabis or stress-related damage.
A Powerful, Delicate System
The takeaway? Your endocannabinoid system is an incredible natural mechanism designed to help you respond to life emotionally, physically, and mentally. Cannabis can tap into this system, but it’s not a perfect substitute for what your body creates.
THC doesn’t "listen" to the body the way your own molecules do. It doesn’t show up only when needed or leave quietly when the job is done. And while cannabis may help some people medically, its use especially in younger brains or without medical guidance can come with real risks.
How to Support Your ECS Naturally
- Exercise – especially aerobic and moderate-intensity workouts
- Omega-3 fatty acids – support endocannabinoid production
- Stress management – chronic stress can disrupt ECS signaling
- Sleep – quality sleep enhances ECS balance
- Mind-body practices – yoga and meditation may help regulate ECS activity
Understanding your ECS and the genetics behind it helps us make better choices about how we manage stress, and health. Just like a symphony, your body needs harmony, and your endocannabinoid system is the conductor helping to keep everything in tune.