The genetics of your endocannabinoid system can influence your cognitive abilities. Here are 3 examples with variants in the CB1 receptor gene.

The endocannabinoid system underlies many aspects of learning, memory, and other aspects of cognition. We know this partially because THC impacts many different types of memory. lt should be no surprise then that genetic variants in the endocannabinoid system also influence cognition.

I won’t go as far as to say that your endocannabinoid system determines your IQ, since there are many other factors that contribute to this. But the studies below indicate a clear association between optimal functioning of your endocannabinoid system and cognitive processes which contribute to IQ.

The cannabinoid CB1 receptor is a particularly important player  here.  The gene for the CB1 receptor (known as CNR1) has several genetic polymorphism which affects its function. The following 3 CB1 receptor polymorphisms were examined in the studies below:

  • AATn repeat: This is a microsatellite repeat polymorphism in the 3′ untranslated region of the gene. It is an “AAT” sequence which repeats itself anywhere from a low number of times (<5) to a high number of times (>15). The number of repeats may influence gene translation.
  • rs2180619: A single nucleotide polymorphism (A or G) in the promoter region of the gene, which potentially affects receptor expression
  • rs1406977: Another single nucleotide polymorphism (A or G) in the promoter region of the gene, which potentially affects receptor expression


1. Working Memory & CB1 Genetic Variants


Working memory is what allows us to consciously manipulate information. Doing math in your head uses working memory, although there are many other examples.

Four different studies have examined the relationship between human CB1 receptor genetics and working memory in healthy subjects. Importantly, subjects were not currently using cannabis, which could skew results.

The first two studies (a 2013 study and 2014 study) examined CB1 receptor polymorphisms that were previously studied in other contexts. Here is what they found:

  • Subjects with fewer AAT repeats had significantly better working memory performance than subjects homozygous for long AAT repeats.
  • Subjects with the rs2180619 A/A genotype performed better in a task of working memory compared to G/G subjects, particularly when they needed to handle a high amount of information at one time.

2015 study took a slightly different approach. Instead of starting with a particular CB1 polymorphism in mind, they searched a gene expression database from human cadavers. They looked specifically at expression in the prefrontal cortex, where most of the information processing in working memory occurs.

They discovered that the rs1406977 polymorphism was associated with CB1 gene expression in this brain area and subsequently tested its effect on the working memory of (live) human subjects. They found that A/A subjects had better working memory performance than G carriers. This was subsequently confirmed by a 2016 study.

Interestingly, A/A was the genotype associated with higher CB1 gene expression in the prefrontal cortex. These results indicate that a higher level of CB1 receptor may lead to better working memory.


2. Executive Functioning & CB1 Genetic Variants


Executive functioning is a set of processes needed for goal-directed behavior. These include things like attentional control and planning. Executing functioning is impaired in various diseases such as ADHD, addiction, and schizophrenia.

One marker of executive functioning is the auditory event-related potential (ERP). The basic idea is that a specific EEG brain wave (the P300 wave) is measured while the subject listens for different tones which they have to respond to as quickly as they can. Higher P300 wave amplitudes are associated with better attentional resource allocation.

Two studies have shown an association between CB1 receptor genetics and ERP:

  • 1997 study performed in a population of drug addicts showed that longer AAT repeats were associated with decreased P300 amplitude in the frontal lobes.
  • A 2011 study similarly revealed a marked decrease in frontal lobe P300 amplitude in healthy subjects homozygous for longer AAT repeats

These results indicate that the CB1 receptor is involved in attention and likely other executive functions.


3. Procedural Learning & CB1 Genetic Variants

[Wikimedia Commons]

Procedural learning is the process of acquiring new motor sequences. Learning to drive, play a sport, roll a joint, or do a dab all require this procedural learning.

A 2011 study examined the association between procedural learning and the AATn polymorphism. Healthy non-cannabis users performed a procedural learning task and were divided into high and low performance groups depending on how well they did.

The carriers of longer AAT repeats were more frequent in the high performance group and carriers of shorter AAT repeats were more frequent in the low performance group. The authors speculate that the long AAT carriers may have higher CB1 expression in their striatum, allowing greater coordination of learned movements.


Conclusion on Endocannabinoid Genetics and Cognition

Your endocannabinoid genetics are important for several aspects of learning, memory, and attention. If you have genotyped yourself with 23andMe, you can determine which of these variants you have (although 23andMe does not test for all 3 of these). I will soon add details on my running list of cannabinoid-related polymorphisms genotyped by 23andMe.

Things become more complicated when you add THC and CBD to the mix. I have already covered how a COMT polymorphism influences susceptibility to memory impairments of THC. There is a lot more research in this area that I will write about soon!

Last modified: January 5, 2018

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