August 13, 2020

Genetic influences on THC Craving and Withdrawal

THC, while not physically addictive in the way of alcohol or opiates, can be habit-forming for some people. As someone who's pro-legalization and pro-cognitive liberty, I think it's just as important to talk about the risks of cannabis use just as much the benefits. While addiction is a complex, multi-factor issue, some people may be more or less genetically prone to craving and withdrawal effects of THC.

Taking a break from cannabis is easy for some people. But, for others it can be a real challenge. 

Anyone who's used cannabis for any amount of time knows there's a sweet spot of frequency and dose that's different for each person.

For some people, it's much hard to regulate that ideal frequency, and find themselves consuming more than they want to. The dopaminergic effects of THC can reinforce addictive behavior just like any other substance that catalyzes a pleasure/reward response.

But, why is it so easy for some people to take a break and regulate their useage while it's more difficult for others?

As practitioners begin to use psychoactive cannabinoids like THC for treating different conditions, it's important to help clients understand how to appropriately regulate their use as well.

Genetic Influences on Craving and Withdrawal

Variants in the FAAH and CNR1 genes are associated with greater withdrawal symptoms. So, craving THC may be partially genetic in origin. 

The cannabinoid receptor 1 gene (CNR1) codes for one of two main endocannabinoid receptors in the body. Subtle variations in the receptor structure seem to influence a number of different traits, including craving and withdrawal.

And, the FAAH gene codes for the fatty acid amide hydrolase enzyme, an important enzyme that breaks down anandamide, one of the body's main endocannabinoids.

The CC variant of FAAH rs324420 is associated with greater withdrawal symptoms. Those with the CC variant tend to carry lower levels of their own endocannabinoids to begin with. While this is an oversimplification, it's possible that the craving/withdrawal effects come from having a more exaggerated response to exogenous cannabinoids when removed, due to the wider gap in cannabinoid tone verses those with preexisting higher levels of anandamide.

And, when combined with the risk allele of CNR1 rs2023239, it becomes more intense. Brain scans have shown greater activation in craving-related parts of the brain 3 days after abstinence. 

The greater the total number of risk alleles in CNR1 rs2023239 and FAAH rs324420, the greater activation of critical reward processing areas of the brain (NAc, thalamus, OFC, ACG) with cannabis-related visual cues 3 days after abstinence in regular daily users
CNR1 rs2023239 C carriers show higher withdrawal and higher depression scores after 5-abstinence from THC. From doi:10.1111/j.1360-0443.2008.02292.x 

How to Use this Information

So, how to use this information? Can understanding these dynamics actually help regulate cannabis use in a positive way?

I've worked with many clients that would say "yes!"

Understanding how you're wired can help you make different decisions. Or help you find different coping strategies. 

These two genetic variants aren't the whole picture either. In my comprehensive endocannabinoid training I cover 8 other variants related to craving. And, over 50 other variants related to other areas.

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.


Filbey, F., Schacht, J., Myers, U. et al. Individual and Additive Effects of the CNR1 and FAAH Genes on Brain Response to Marijuana Cues. Neuropsychopharmacol 35, 967–975 (2010).

Haughey, H. M., Marshall, E., Schacht, J. P., Louis, A., & Hutchison, K. E. (2008). Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes. Addiction, 103(10), 1678–1686. doi:10.1111/j.1360-0443.2008.02292.x

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