Food and Behaviour Research

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Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice

Hao S, Avraham Y, Mechoulam R, Berry EM. (2000) Eur J Pharmacol.  392(3): 147-56. 

Web URL: View this and related abstracts via PubMed here


This investigation reports the possible role of the endocannabinoid anandamide on modulating the behavioral and neurochemical consequences of semi-starvation.

We studied the effect of very low dose anandamide (0.001 mg/kg) administration on food intake, cognitive function and catecholaminergic and serotonergic pathways in two murine brain areas concerned with appetite (hypothalamus) and learning (hippocampus), and the peripheral corticosterone response to the stress of 40% diet restriction.

Anandamide-treated mice consumed 44% more food (P<0.05) during 1 week of 2.5-h feeding each day.

In the hypothalamus, there were significantly increased concentrations of norepinephrine (P<0.01), dopamine (P<0.05) and 5-hydroxytryptamine (5-HT) (P<0.001).

In the hippocampus, anandamide increased significantly norepinephrine and dopamine, but decreased 5-HT (all at P<0.001). Diet restriction was accompanied in both areas by a significant decrease in all neurotransmitter concentrations that were partially restored by anandamide for dopamine and 5-HT, but not for norepinephrine.

In animals on diet restriction, anandamide significantly improved impaired maze performance. Norepinephrine turnover and plasma corticosterone levels were also raised significantly by anandamide.

The fact that low dose anandamide improved food intake, cognitive function and reversed some of the neurotransmitter changes caused by diet restriction, might have implications for the treatment of cachexia associated with acquired immunodeficiency syndrome (AIDS) and cancer, for mood changes sometimes associated with dieting, and in the extreme case, of patients with anorexia.


Anandamide is one of the main 'endocannabinoids' - substances which activate the same receptors as the active ingredients in cannabis or marijuana.  It was the first of them to be discovered, less than 10 years ago, and it is made within the body from the main long-chain omega-6 fatty acid, arachidonic acid.

This and other endocannabinoids are now known to help regulate numerous brain and body functions including perception, cognition motor control, pain, temperature regulation, sleep - and appetite.

Anandamide acts to increase appetite - and in diet-restricted animals, this study showed that even at low levels, it significantly boosted food intake, improved learning, and affected the concentration of key neuroransmitters in brain areas important for normal appetite and learning.

As the authors note, these findings could have important implications for conditions involving starvation malnutrition, such as the wasting associated with both cancer and HIV, as well as severe dieting for weight loss, and anorexia.