Ten Ways Fatty Acids and the Endocannabinoid System Influence the Brain Together

The brain, the endocannabinoid system, and levels of omega-3 fatty acids in the body are connected through multiple pathways, but the exact nature of these pathways is still to be determined because of the complexity of the endocannabinoid system.

Arachidonic acid (AA), an omega-6 fat, and docosahexaenoic acid (DHA), an omega-3 fat are the two main fats in the brain, and both are essential for optimal brain development and function. However, it's necessary to maintain a crucial balance between omega-6 fats and omega-3 fats. The average Western diet has a ratio of 15:1, and the ideal ratio is thought to be closer to 4:1. This unbalanced intake indicates a person has low to very low tissue levels of DHA and EPA, and also means people consume too much omega-6 fats, primarily from soybean oil and other vegetable oils. The unbalanced fatty acid may be involved in the etiology of chronic diseases such as cardiovascular disease, cancer, and inflammatory and autoimmune diseases.

What does this mean for the endocannabinoid system? Well, research indicates the endocannabinoid system can be regulated by manipulating the dietary omega-6:omega-3 ratio. A diet high in the omega-3 fatty acids, DHA and EPA, have beneficial effects on learning, memory, neuroinflammatory processes and synaptic plasticity and neurogenesis.


The endocannabinoid system (ECS) consists of three primary elements: CB1 and CB2 cannabinoid receptors, endocannabinoid molecules (AEA and 2-AG) the body produces naturally, and the enzymes necessary to ensure endocannabinoids and cannabinoids get used when needed, but quickly destroyed once they’re used.

Read more about these three elements here


One of the ways omega-3s and omega-6 fatty acids work is through the endocannabinoid system, especially when it comes to neuroinflammation, neurogenesis and brain aging (1).  

Ten ways fatty acids and the endocannabinoid system influence the brain:

1. The fatty acids AA, DHA and EPA are precursors to the important endocannabinoids, AEA and 2-AG.

2. Both DHA and EPA significantly increase 2-AG levels.

3. DHA and EPA regulate CB1 and CB2 receptor activity and levels.

4. CB1 receptors, found primarily in the brain and nerves, decrease with age, which may accelerate cognitive decline. Remember, CB1 receptors are shown to be responsive to omega-3 fatty acid intake.

5. There’s research indicating how the endocannabinoid system can be regulated by manipulating the dietary omega-6:omega-3 ratio. The ideal ratio is thought to be around 4:1.  

6. Omega-3 fats and the two endocannabinoids, 2-AG and AEA, play important roles in the regulation of the inflammatory response that happens in the brain.

7. An enzymatic pathway converts omega-3-derived endocannabinoids into more potent anti-inflammatory molecules that predominantly bind to the receptors found in the immune system (2).

8. Together, omega-3 fatty acids and the endocannabinoid system positively modulates many aspects of synaptic plasticity in the brain. A long-term omega-3 fat deficiency may prevent endocannabinoid-mediated synaptic function.

9. The hippocampus is essential for learning, memory formation and consolidation and also important in regulating aspects of emotion, fear, anxiety and stress. DHA and EPA both positively affect the hippocampus by promoting neurogenesis (the process by which new neurons are formed in the brain). Similarly, the endocannabinoid system is essential for neurogenesis in the hippocampus.

10. FAAH is an enzyme that breaks down the endocannabinoid AEA, which means it's quickly turned into arachidonic acid (AA), an omega-6 fatty acid. When AA is broken down, it produces pro-inflammatory prostaglandins, leukotrienes, and thromboxanes – all which intensify inflammation in the brain. This scenario is what makes omega-3 fats so important for maintaining that crucial fatty acid balance. Ingesting cannabinoids (ie: from CBD oil) downregulates the FAAH enzyme and allow more AEA to stick around so less of it is converted into inflammatory AA. 

You thought fish oil was good for the brain before, now we know it’s a natural way to stimulate the ECS, which is even better. Much more research is required to develop the mechanism for how the ECS maximizes the therapeutic potential of omega-3 fats in brain protection and repair.


Supplementing with 3 grams of EPA and DHA per day (the amount the FDA generally recognizes as safe) will drive the body’s % of omega-6’s down to desirable levels or better. Here is more info about DHA and EPA.  

There’s a cool website called essential fatty acid education (efaeducation.nih.gov), which will estimate your omega-3 levels. This allows you to know whether your omega-3’s and omega-6’s are balanced.

Growing evidence suggests a complex interplay between omega-3 and omega-6 fats and the endocannabinoid system. Although the exact mechanism is still to be determined, we do know maintaining adequate levels of the essential fats DHA and EPA, along with arachidonic acid (ARA) is crucial for optimal health.

In Health and Happiness,

Kelly Harrington, MS, RDN

Registered Dietitian Nutritionist for Healthy Goods


1. Dyall S. Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair. Lipids. 2017;52(11): 885-900. 

2. University of Illinois at Urbana-Champaign. Omega-3 fatty acids fight inflammation via cannabinoids. ScienceDaily. ScienceDaily, 18 July 2017.

3. Caramia G. Essential fatty acids and lipid mediators. Endocannabinoids. Pediatr Med Chir. 2012 Mar-Apr;34(2):65-72.

4. Farooqui AA, Horrocks L, Farooqui T. Modulation of inflammation in brain: a matter of fat. J Neurochem. 2007 May;101(3):577-99.

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