Food and Behaviour Research

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Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions

Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodríguez-Puertas R, Layé S, Manzoni OJ (2011) Nature Neuroscience 14(3): 345-50. Epub 2011 Jan 30. 

Web URL: View this and related abstracts via PubMed here


The corollaries of the obesity epidemic that plagues developed societies are malnutrition and resulting biochemical imbalances.

Low levels of essential n-3 polyunsaturated fatty acids (n-3 PUFAs) have been linked to neuropsychiatric diseases, but the underlying synaptic alterations are mostly unknown.

We found that lifelong n-3 PUFAs dietary insufficiency specifically ablates long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens.

In n-3–deficient mice, presynaptic cannabinoid CB1 receptors (CB1Rs) normally responding to endocannabinoids were uncoupled from their effector Gi/o proteins.

Finally, the dietary-induced reduction of CB1R functions in mood-controlling structures was associated with impaired emotional behavior.

These findings identify a plausible synaptic substrate for the behavioral alterations caused by the n-3 PUFAs deficiency that is often observed in western diets.


This groundbreaking research shows a clear mechanism by which diets deficient in omega-3 fatty acids (and with a corresponding excess of omega-6 fats) can profoundly and permanently alter brain development and functioning in ways that predispose to anxiety, depression and other mental health conditions.

The mechanism involves the 'endocannabinoids' - i.e. cannabinoid-like substances that are produced within the body and brain from omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFA).  

The researchers showed that omega-3 deficiency in early life prevents the establishment of normal endocannabinoid signalling in brain areas important for emotional regulation, and furthermore, that this abolition of function is permanent.

Although caution is always needed in generalising from studies of animals to humans, the researchers note that these findings could help provide a mechanistic explanation for the high rates of anxiety, depression and related conditions already associated with omega-3 deficiencies in both animals and humans. 

It is also very sobering to note that relative omega-3 deficiencies are a key characteristic of modern, western-type diets eaten by most humans in developed countries (and increasingly in developing countries too).

For an accessible news article explaining this research, and its very important implications for the links between nutrition and mental health, see: