August 4, 2020

Cannabinoid Receptor Genetics and Stress Response

Cannabinoids can be profoundly helpful for some people to help them relax or deal with stress.

The endocannabinoid system is an important part of the stress response. Cannabinoids and receptors inhibit neurons in the Hypothalamic-Pituitary- Adrenal (HPA) axis. This influences the release of stress hormones like cortisol and ACTH.

And it turns out that variants in the cannabinoid 1 receptor gene (CNR1) may impact your ability to calm down after a stressful event.

CNR1 Genetics

The CNR1 gene codes for the cannabinoid receptor 1, one of two main receptors that are responsive to both endo (produced by the human body) and exo (plant-based) cannabinoids. Small variations in the code of this gene or SNPs that vary naturally from person to person can create differences in the way the receptor functions. And, these variations can create different outcomes in how people respond to stress.

In a study published in the Nature journal Translational Psychiatry, Scientists exposed 150 healthy subjects to a "startle event" and measured startle response and subjective fear reporting over time. 

The capacity to calm back down is known as "fear extinction." Or, the ability to return a non-fear/anxiety state after experiencing fear-based arousal.

They found that people with the AA variant in rs2180619 took a long time to extinguish their fear. On average, they were still in an elevated state after the testing was done.

And, people with the GG or AG variants were able to come back to baseline quickly. 

(Heitland et al, 2012)

But, it's not all good or bad. In another study, it was found that AA variants were likely to have superior working memory. 

And, interestingly, the G allele is hypothesized to code for lower density of CB1 receptors in the brain while AA may code for higher density.

Most genetic variants carry an adaptation advantage for different traits or environments. For a more thorough discussion of this on cannabis and human genetics in another article I wrote, click here.


So, what does this mean?

Well for one, it's possible that AA variants might benefit more from using CBD or THC for stress relief. 

And, it’s possible that GG or AG variants might not get as much benefit. 

There's not clear evidence of this either way yet, but from my personal experience and limited clinical observations with clients, this seems to hold true so far.

In a more general sense, AA carriers would benefit from developing self-regulation skills and focusing on improving vagal nerve tone.

Of course, these aren’t the only genetic factors. Traits are complex and there are other genes known to impact stress response. 

For example, is there an interaction between a gene like FAAH that influences endogenous endocannabinoid levels and the CNR1 varaint discusse above? Do people with higher anandamide levels, which is associated with typically a better stress/anxiety response, have better fear extinction regardless of their CNR1 variant?

Taking a polygenic approach that looks at the interaction between genes is important, and this is the approach I'm teaching in the upcoming 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.

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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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