Balancing (and Imbalancing) Your Endocannabinoid System

Written by: Genevieve R. Moore PhD

Many of us are searching for balance: mind/body balance, work/life balance, balance in relationships, a balanced diet, a balanced immune system…

If you’ve been searching for balance, you already may have heard that CBD is a valuable ally on your quest. Cannabidiol (CBD) is used by more and more people around the world — for everything from regulating stress and mood, to managing pain, fighting runaway inflammation, and more.

But do you know why CBD is so beneficial for your physical & psychological well-being?

Just like you, your body is in a constant quest for balance — or in Biological terms, “homeostasis.” Homeostasis depends on your body maintaining a stable internal environment. Overall homeostasis is dependent on the homeostasis of each variable within your body — countless things like blood glucose, body temperature, blood pressure and more.

It turns out that one of the most important tools your body uses to achieve homeostasis is the endocannabinoid system (ECS). This natural system was only recently discovered — what started as an investigation into how cannabis “works” quickly revealed a complex interplay of neurotransmitters called endocannabinoids (eCB) and their receptors throughout the body.

There are now thousands of scientific articles, mostly published in the last decade, detailing the many ways that endocannabinoids support the health of our bodies and minds. eCBs are deeply rooted in our evolutionary pasts and are used to bring balance to many different tissues of the body. Here are just a few of your body’s functions that endocannabinoids help balance:

  • The immune system
  • Cardiovascular health
  • Digestion
  • Mental health
  • Eye health and intraocular pressure
  • Memory
  • Appetite
  • Reward circuits (which make exercise, sex, or drugs enjoyable)
  • Skin health
  • Neuroprotection after trauma
  • … and more.

Your Body’s Constant Balancing Act

So how does your body function if its endocannabinoid system gets out of balance? Why doesn’t everything break down completely?

Consider this analogy: you walk miles to work every day, until you hurt your left ankle. Whereas normally your weight was balanced evenly on your right and left legs, now you limp & your right leg takes almost all the weight.

Now even though your weight is imbalanced, you are able to walk because your body has found a new, temporary adaptation. However, if you don’t heal the injured ankle and continue limping, the strain could irritate & damage your muscles & joints over time...

Similarly, your body’s neurotransmitters — substances like serotonin, dopamine and endocannabinoids — can sometimes be thrown out of balance. Your body’s well-intentioned attempt to compensate, like limping, can be detrimental to your long-term health.

For example, if your neurotransmitter levels are too low or high, your cells might adjust by increasing or decreasing their receptors — becoming over- or under-sensitized.

Alternatively, other tissues and systems within your body might have to compensate in other ways — which could manifest as physical and psychological maladies.

One of the first steps you can take to disrupt this pattern and restore balance to your body is to figure out where the imbalance originated. The endocannabinoid system is complex and there is not a one-size-fits-all solution to an imbalanced ECS — some of us will benefit from boosting our bodies’ production of eCBs, while others might benefit more from relieving the burden of an overstimulated ECS.

Causes of ECS Imbalance

Emotional Stress:

Most of us think of “stress” purely as a negative. However, when faced with danger, the stress response is incredibly useful and helps humans to quickly respond to threats and survive. The real problem is when that survival mode becomes constant, unrelenting.

At first, when exposed to stress, your body reduces levels of anandamide (the feel-good eCB) — triggering feelings of agitation, anxiety or “stress.” Simultaneously, your body increases levels of 2-AG, which dampens your perception of pain and activates memory to help you escape the situation and avoid danger in the future.

Eventually, if stress becomes chronic, your body must adapt to the fact that it cannot escape from the stressor. Chronic stress and high 2-AG levels wind up overstimulating CB1 receptors in the brain, so the brain compensates by decreasing its CB1 receptors.

With fewer eCB receptors in your brain, it can be difficult to maintain the emotional balance that eCBs normally provide. Indeed, mice with limited CB1 receptors are used to study depression. Similarly, people with unusual versions of the CB1 gene are more susceptible to addiction, bipolar disorder and major depression.

Poor Diet:

You probably have heard that eating a western diet packed with sugars and unhealthy fats is bad for your health and your waistline. Did you know that these diets are also rough on your endocannabinoid system? eCBs control your appetite (which is why THC stimulates hunger), and western diets can lead to increased production of eCBs in the intestine and circulatory system, making them hungrier.

Added to this problem is the finding that fat cells produce even more eCBs, which means that overweight people often have higher levels of eCBs stoking their hunger, making it harder to lose weight.

Fortunately, increasing consumption of omega-3 polyunsaturated fatty acids (PUFA) and shifting the ratio away from omega-6 PUFAs can improve the situation. Though omega-3s won’t lower your overall production of eCBs, your body will produce a better ratio of “good” eCBs. These better eCBs have lower binding affinities for many of your body’s eCB receptors (which reduces the burden of an overstimulated ECS).


Recreational and pharmaceutical drugs can sometimes help us feel better, but scientists are only starting to uncover how their long-term use can have profound effects on the endocannabinoid system. Some drugs, like alcohol, stimulate our bodies to increase production of endocannabinoids.  Chronic consumption of recreational (and perhaps some pharmaceutical) drugs like alcohol and THC can overstimulate our eCB receptors, leading to a tolerance effect where CB1 receptors become downregulated in the brain.

This also might be a large reason for the addictive nature of certain drugs. Studies with rodents suggest that CB1 receptors become even more sparse when alcoholics go into withdrawal, and don’t return to normal levels for weeks or longer.


Our endocannabinoid systems can become imbalanced for many reasons that are beyond our control. People suffering from a wide variety of physical diseases and psychological disorders find relief from their symptoms with cannabis or CBD — which suggests an imbalance in their endocannabinoid systems. Indeed, research is just starting to find these associations for cancer, Parkinson's disease, multiple sclerosis, depression, PTSD, glaucoma, arthritis, and schizophrenia, to name a few.

Scientists are still deciphering which diseases are caused by imbalances in the ECS, and which diseases cause the ECS to become imbalanced (but it’s probably a bit of both in most cases). Either way, many diseases are an indication that your endocannabinoid system may also be impaired.


Unfortunately, some people are born with sub-optimal endocannabinoid systems. Your DNA contains the blueprint for all the pieces of your body, including your neurotransmitters and receptors. There are millions of locations along your DNA that differ from the average person and all these many differences add up to create endocannabinoid systems that are unique to each individual.

An example of how this works was recently discovered — about 20% of Americans have a mutation in a single gene that degrades anandamide, one of your body’s endocannabinoids. People with this mutation end up with higher levels of anandamide in their systems and a reduced reaction to stress, although other effects of this gene could include a higher risk for obesity.

Restoring Balance to Your ECS

Many of us struggle with at least one of the problems mentioned above. Unfortunately, that means that many of us also struggle with imbalances in our endocannabinoid system — which makes sense given the large number of people who are currently using CBD supplements and other cannabis products to restore balance into their lives.

If you want to restore a healthy balance to your endocannabinoid system, here are some natural ways that you can adjust your body’s endocannabinoid levels:


You know how people claim to get an endorphin rush from intense physical activity? Well, scientific evidence indicates that the “runner’s high” is actually caused by endocannabinoids. An hour or more of moderate intensity exercise can raise your blood levels of anandamide. The runner’s high can bring temporary pain reduction, reduced anxiety (post-exercise “glow”), and/or euphoria.

Even if you dislike intense physical activity and exercise less than an hour per week, whatever amount (and whatever type) of exercise you do will increase your levels of both anandamide and 2-AG and help boost your mood. Regular exercise can also help you maintain a healthy weight and manage your stress levels, both of which should help keep your ECS balanced.

Fish oil:

Most American diets contain an unnaturally high ratio of omega-6:omega-3 fatty acids. This has an inflammatory effect on the body. By consuming foods that have a high omega-3 content, like seafood and fish oil, you can bring this ratio back into balance.

Fatty acids are converted by your body into endocannabinoids, and increasing your omega-3 consumption can bias your body towards making endocannabinoids that are ideal for people with overactive ECS and/or inflammatory issues. These “better” endocannabinoids have lower binding affinities for many of your body’s eCB receptors (which reduces the burden of an overstimulated ECS), but also a higher affinity for the eCB receptors of the immune system, where they have an anti-inflammatory effect. Not into eating fish? Try supplementing your diet with flaxseed oil, chia seeds, and especially hemp milk.


Chronic abuse of THC and alcohol can over-activate your CB1 receptors, causing your brain to decrease the number of receptors it makes available. Although this imbalance is particularly difficult during the withdrawal period, evidence shows that the receptors can return to their natural levels after a month of abstinence.


A surprising number of spices and exotic ingredients contain phytocannabinoids — plant compounds that interact with the endocannabinoid system. In addition to cannabis, phytocannabinoids (both receptor-stimulators as well as enzyme-inhibitors) can be found in: chocolate, maca, black pepper, nutmeg, kava kava, truffles, ginger, hops, and many essential oils (beta caryophyllene). Because each phytocannabinoid interacts with the ECS in a slightly different way, self-experimentation is the best way for you to discover which of these phytocannabinoids are best-suited for your needs.


Although CBD is technically also a phytocannabinoid, its effects on the endocannabinoid system are very different from other classic phytocannabinoids like THC. Instead of stimulating your ECS (and potentially overstimulating it), CBD modifies CB1 receptors so that they are harder to activate and over-activate. CBD also helps boost your natural levels of endocannabinoids by inhibiting their reuptake and degradation. This dual activity of CBD on the endocannabinoid system, as well as its myriad benefits on other systems (like serotonin and pain receptors) has a balancing effect for many people.


Many of us know that sunlight helps our bodies produce Vitamin D and can boost our moods — especially in the winter. It turns out that 15 minutes of solar ultraviolet radiation also raises levels of 2-AG, an important endocannabinoid. If you’re looking for a boost, have lunch outside or take a stroll in the sunshine. (However, long-term UV exposure can damage your cells’ DNA and contribute to skin cancer, so make sure your skin drinks the sunlight responsibly!)


Okay, there isn’t any scientific evidence per se that meditation influences your endocannabinoid levels (at least not yet), but taking steps to reduce your stress levels WILL help prevent the overstimulation (and the subsequent downregulation or “de-sensitization”) of your eCB receptors.


Surprisingly, there is evidence that for both women & men, orgasms from masturbation increase the circulating levels of the endocannabinoid 2-AG. Although this link hasn’t been established yet for partner-triggered orgasms, the ECS is intimately tied to sexual pleasure and reproduction.


A 24-hour fast will temporarily boost your levels of 2-AG (although a good portion of those endocannabinoids will be employed with the task of making you hungry). However, it is intriguing that many of the touted benefits offered from intermittent fasting — inflammation reduction, heart health, cancer prevention, neuroprotection — overlap with the benefits of a balanced endocannabinoid system.

Balance: the Secret to Sustainability

If you want your body to function optimally — and to function optimally for a good long time — then it’s important to take care of the different systems within your body that help it maintain homeostasis.

If your ECS imbalance stems from lifestyle influences like your diet, then finding a healthy balance can be achieved by adjusting your lifestyle — easier said than done, but doable.

Unfortunately, it’s difficult to change your environment and virtually impossible to change your genetics. If your imbalance comes from a stressful work environment, disease, the luck of your genetics, or some other factor beyond your control, then you might consider trying a combination of some of the options discussed in this article.

Researchers are still deciphering the nuances of the endocannabinoid system. Science doesn’t yet have the complete solution for restoring balance to the endocannabinoid system — and the solution will most likely be unique to each person.

We wish you the best of luck on your search for balance!

More articles by: Genevieve R. Moore PhD

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