Our work

Your brain own 'drugs'

Endocannabinoids are important regulators of metabolism – both in brain and in peripheral tissues. To understand the effect of a certain (dietary) intervention, it is important to get the bigger picture of the endocannabinoid system. TNO developed a robust and validated LC-MS/MS based platform to evaluate multiple compounds at the localization that matters in metabolism.

The endocannabinoid system refers to a group of neuromodulatory lipids that are widely present throughout the body. This important group of bio-active molecules is involved in a variety of physiological and biological processes, including mood, inflammation, regulation of food intake and metabolism. Endocannabinoid are considered to be synthesized 'on demand' in various localized tissues but are also rapidly broken down again, putting high demands on analytics and interpretation. The cannabinoid type-1 receptor (CB1) is mediating these physiological and biological processes, but endocannabinoids and related compounds are also known to bind to other receptors, such as GPR119, PPAR-gamma and TRPV-1.
The effects of these compounds can be contrastive: increased brain levels of AEA are known to promote food intake, but OEA reduces food intake and body weight gain(1).

Analytics at TNO

TNO offers a robust and validated LC-MS/MS based platform for the simultaneous quantification of AEA, O-AEA, 2-AG, 2-AG ether, DHEA, EPEA, DEA, DLE, NAGly, NADA, OLDA, OEA, PEA, and SEA in plasma, liver, ileum, and adipose tissue(2). With this analysis technique, we have established that adipocytes can convert n-3 fatty acids to their endocannabinoid analogues(3). In other work, we investigated fasting and post-prandial endocannabinoid levels in humans, showing a correlation with specific fatty acids(4). This study also demonstrated that AEA and OEA are correlated with BMI. TNO has the knowledge and analytical capability to clarify the complex role of this import group of neuromodulatory lipids on vital physiological processes such as mood, inflammation, regulation of food intake and metabolism and how to put these signal molecules into practice by dietary intervention and healthy food concepts.

Scientific references

1) Li, Jones and Persaud
Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas.
Pharmacol Ther 2011

2) Balvers, Verhoeckx and Witkamp
Development and validation of a quantitative method for the determination of 12 endocannabinoids and related compounds in human plasma using liquid chromatography-tandem mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci 2009

3) Balvers, Verhoeckx, Plastina, Wortelboer, Meijerink and Witkamp
Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties.
Biochim Biophys Acta 2010

4) Joosten, Balvers, Verhoeckx, Hendriks and Witkamp
Plasma anandamide and other N-acylethanolamines are correlated with their corresponding free fatty acid levels under both fasting and non-fasting conditions in women.
Nutr Metab 2010


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