Beat “Brain Fog” With The Cannabinoid System (CNR1)

In this post, we’ll be talking about the CNR1 gene, the general role it plays in the brain’s cannabinoid system, and how certain variants may increase your risk of experiencing “brain fog” and other chronic cognitive issues.

However, it is important to keep in mind that the brain’s cannabinoid system is very complex, and can influence many different aspects of your health! Therefore, for a more detailed look at the cannabinoid system and the many different roles it plays in your body and brain, our comprehensive SelfHacked post on the cannabinoid system would be a great place to start!

You might also want to check out our other SelfDecode blog posts on CNR1, which go into even greater detail about the influence this important gene can have on important health issues, such as lectin sensitivity.

In this post, we’ll focus specifically on the role of the CNR1 gene in brain fog and other cognitive issues – but this gene also has many other important functions that are worth looking into!

The CNR1 gene codes for the type-1 cannabinoid receptor (CB1 receptor), one of the main receptors responsible for stimulating the brain’s cannabinoid system [R, R].

Cannabinoid receptors are highly expressed in the brain’s limbic system, which is why the cannabinoid system is highly involved in mood, wakefulness, and the regulation of the stress response [R, R, R, R].

These receptors are also prominent in several key areas of the brain involved in cognitive processes, such as the hippocampus. This gives the cannabinoid system a key role in several important biological and cognitive processes, including synaptic plasticity, learning, and memory [R, R].

Cannabinoid receptors are also widespread throughout the gut nervous system, where they play a major role in counteracting inflammation [R, R, R].

In general, the variants that people carry in the CNR1 gene determine how well their cannabinoid receptors work. Because this system has so many different roles in the body, abnormal cannabinoid receptor activity can lead to a complex variety of symptoms, such as increased inflammation, fatigue, elevated stress, impaired learning and memory, and even mood problems [R, R, R].

Interestingly, this range of symptoms closely matches those commonly seen in people who have “brain fog”. Therefore, the variants you carry in this gene can affect your cognitive ability by determining how vulnerable you are to brain fog.

The CNR1 gene codes for one of the main types of receptors involved in stimulating your brain’s cannabinoid system. Abnormalities in the cannabinoid system can lead to a wide variety of symptoms, many of which are often seen in people with “brain fog” and other tricky cognitive issues.

You can see your genotype for the CNR1 SNP rs1049353 in the table below:

The two possible alleles to have are ‘C’ and ‘T’. When it comes to avoiding chronic cognitive issues such as brain fog, it’s better to have the more common ’CC’ genotype (as about 55% of people of European descent do).

This is because the minor ‘T’ allele has been linked to reduced CB1 receptor activity. In turn, reduced CB1 activity has been linked to a wide variety of conditions that can all contribute to the overall pattern of symptoms seen in “brain fog” and other tricky cognitive issues [R].

How Does CNR1 Cause Brain Fog?

First, reduced CB1 activation can have a variety of significant negative effects on mood.

For example, a large number of animal studies have found that reducing, blocking, or knocking out CB1 receptors can cause a number of negative mood-related effects, such as:

• Increased symptoms of depression [R]
• Increased sensitivity to stress [R, R, R]
• Increased vulnerability to anxiety [R, R, R]

Similar findings have also been reported in humans as well. For example, blocking CB1 receptors results in significantly reduced overall motivation and a lack of positive emotion (“anhedonia”) [R] – two symptoms that can definitely interfere with your mood!

Similarly, another study found that blocking CB1 receptors increases anxiety and other negative mood symptoms (such as dysphoria) in humans [R], which further reinforces the connection between the cannabinoid system and common mood problems.

Second, lower cannabinoid receptor activity can have significant negative cognitive effects as well.

For example, knocking out CB1 receptors in mice results in significantly reduced levels of BDNF, a brain growth compound (neurotrophin) that is critical for neurogenesis and synaptic plasticity [R, R].

Relatedly, knocking out CB1 receptors in mice also contributes to more severe age-related cognitive impairments [R, R, R]. These negative cognitive effects are likely due to increased (neuro-)inflammation [R], which CB1 receptors normally play a role in counteracting [R].

All together, the negative effects of reduced cannabinoid system activity overlap with many mood-, cognitive-, and inflammation-related symptoms commonly associated with brain fog. This means that people who carry the ‘T’ allele are likely at greater overall risk for brain fog and other chronic cognitive issues.

Carriers of the ‘T’ allele for rs1049353 are at relatively increased risk of experiencing brain fog and other tricky mood- and cognitive issues – most likely because their brain’s cannabinoid system is under-active.