July 20, 2020

Do You Have High or Low Endocannabinoid Levels? The FAAH Gene

Fed up with hearing how CBD is the cure for... EVERYTHING? How it can help you win the lottery, have your house clean itself, and make your crush fall wildly, deeply in love with you? (These claims are not FDA approved.) 

Well, although it's NOT a miracle elixir for everyone, there's a good reason why it can help with anxiety, sleep, pain, inflammation, depression, and more.

See, endocannabinoids play a role in nearly every system in the body. Cannabinoid receptors have been found on almost every cell type


Anandamide, one of the main endocannabinoids in our body, is involved in stress response, anxiety, depression, ADHD, pain response, appetite regulation, vasorelaxation and blood pressure regulation, immune response, and addictive behavior and more. 

It acts as a homeostatic regulator. Or, a balancing agent, in the body. For example, it turns off neurons that are over-firing. And, it can help turn on ones that are under-firing. 

A common genetic variant in the FAAH gene (rs324420) is associated with levels of anandamide.

The FAAH Gene

The FAAH (Fatty Acid Amide Hydrolase) enzyme helps break down anandamide. So, people with higher levels of FAAH (rs324420 CC variants) tend to have lower levels of anandamide. And, people with lower levels of FAAH (rs324420 AC or AA variants) tend to have moderate to higher levels of anandamide. 

For a primer on what an "rs number" or SNP is, read this article here.

Neither one is good or bad. There are different traits and effects associated with both low and higher levels. 

FAAH and Happiness

Anandamide has many functions but is heavily involved in mood, stress and anxiety. 

A 2017 study looked at how many "A" variants were present in different countries around the world. The more A variants, the higher levels of self-reported happiness. The results showed a strong correlation. 

From: https://doi.org/10.1007/s10902-015-9712-y

Other studies have shown that A carriers tend to have less anxiety and better stress management. 

FAAH and Fear Extinction

The AA and AC variants of FAAH (higher anandamide variant) have also been associated with generally lower anxiety and better fear learning according to this study.

Rare Case Study

Additionally, there is a case study of woman with rare microdeletion in FAAH, not a common variant, that caused total loss of enzyme function. This causes her to have extremely high endocannabinoid levels and she essentially feels no pain and doesn’t experience anxiety or low moods.

She was genotyped after she required no post-operative anesthesia for a normally painful procedure and had a lifelong history of painless wounds that healed quicker than normal.

While it seems like anandamide might some kind of miracle compound based on her story, there are also potential downsides to higher levels.

FAAH and Obesity

Another important aspect of anandamide seems to be involved in metabolism, fat storage, eating behavior.

While the A allele of FAAH is associated with lower anxiety and higher happiness, it also is associated with higher rates of obesity and decreased leptin sensitivity, especially the AA variant.

So, like many other gene variants, the differences in the FAAH rs324420 are not good or bad, but simply create different tendencies that are better suited for different environments and different lifestyles.

A carriers may be more stress resilient, but more prone to metabolic issues. And, on the flip side, CC carriers may be less prone to obesity, but more prone to anxiety and stress.

CBD can act as an FAAH inhibitor and increase anandamide levels, so considering that in combination with someone's FAAH variant can be helpful.

FAAH and Response to THC

Finally, another thing that FAAH and anandamide levels seems to influence is overall response to THC.

A 2008 study looked at 40 regular cannabis users who abstained for 24 hours and then smoked a joint and rated their mood after smoking.

The CC carriers tended to report a higher mood rating after consuming cannabis, but a lower rating before hand.

And, the AC and AA carriers reported the opposite, having a higher mood score beforehand, dropping significantly about 30-60 minutes after smoking.

Does this mean CC carriers do better with THC in general? Perhaps, but it also could mean that A carriers get more general mood benefit when not directly high (abstaining for 24 hours) but not necessarily while they're high. And, it might mean the opposite for CC carriers. That they get a better mood boost while under the influence of THC, but lower mood when abstaining.

This is a limited study, and more work needs to be done, but consider this in the context of the endocannabinoid deficiency hypothesis. Those with lower levels of anandamide might get more of an acute mood benefit from activating CB1 receptors with THC, but when that wears off experience a sharper drop in mood. And on the flip side, AA and AC carriers might be prone to experiencing more imbalance from acute THC use. This is an oversimplified model, but it's still use to consider.

Other studies do support the idea that CC carriers can experience more withdrawal and craving symptoms when ceasing THC use. So, again, it's a complex balance.

Using this Information

Understanding these tendencies (in combination with the myriad of other genes that influence these dynamics) can help you or your clients more precisely align with the right health-creating inputs. For example, if an rs324420 AA client wants to lose weight, adding more cannabinoids into their system, already higher in endocannabinoids, may be counterproductive. And, on the flip side, if a CC carrier wants to gain weight, adding cannabinoids into the system may be a helpful strategy.

Or, if improving mood and resilience is a goal, it might be helpful to know FAAH genotype as well. 

But, FAAH is only one component - there are numerous other genes and factors that need to be taken into account. It's helpful to learn their individual functions, but when assessing a person, taking a polygenic approach that looks at the interaction between genes is important. This is the approach I'm teaching in the CannaDNA training.

The Big Picture

Response to cannabinoids has many components. I like to think of it as a combination of:

  • Set (Mindset, psychology)
  • Setting (Where and when are you using it)
  • Genetics (Your baseline tendencies)
  • Epigenetics (Your current health status)
  • Strain (Combination of cannabinoids and terpenes)
  • Method of Ingestion (vaped vs oral vs smoked)
  • Dose
  • Quality of Product

Some of these factors you may have more control over than others. You can't control your genetics but you can match the right inputs to your genetics.

This means potentially choosing a different food, herb, supplement, or lifestyle choice to create better epigenetic expression.

Having a better understanding of ALL the components listed above can help you optimize you or your client's health in a more strategic, precise way.

If you're curious about analyzing your endocannabinoid genes, send me a message. I helped develop the Apeiron Endocannabinoid Genetic Panel that can give you a better understanding of the dynamics of how you respond to THC, CBD, and naturally create your own endocannabinoids. I look at this and 50+ other variants for a comprehensive look into how to best use cannabinoids.

Or if you're a practitioner and are interested in providing your clients with better answers about cannabinoids, you can learn more about a comprehensive training on precision genetic analysis I've put together with Dan Stickler, MD by clicking here.

Discover the Next Version of Yourself
Are you ready to feel and perform better today while investing in your future self? Would you like more clarity and presence to flow into your relationships, productivity, and greater purpose? I blend data-driven testing, holistic coaching, and a complex-systems perspective to create custom protocols that take your whole being into account. I'm skilled at navigating personal growth and transformation, and can help pair you with the right techniques for the development of your physiology, mind, and spirit. Can you imagine feeling 100%? If so, I can help you get there.
Legal Disclaimer: I am not a doctor and do not treat, diagnose or cure any disease, illness, or condition. I work from a whole-systems perspective to optimize physiological function in order to promote wellness. Nothing on this site should be misconstrued as medical advice or therapy of any kind. All information on this website is for educational and/or entertainment purposes only. Talk to your doctor before making any changes to your diet, habits, or routine that may impact your health. 
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