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Biochem Pharmacol. 2018 Nov;157:43-50. doi: 10.1016/j.bcp.2018.08.040. Epub 2018 Aug 30.

When orexins meet cannabinoids: Bidirectional functional interactions.

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Faculty of Experimental Sciences, Universidad Francisco de Vitoria, UFV, 28223 Pozuelo de Alarcón, Madrid, Spain; Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, 08003 Barcelona, Spain. Electronic address:
Institute of Neurosciences, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Integrative Pharmacology and Systems Neuroscience, IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain. Electronic address:


A growing body of evidence suggests the existence of biochemical and functional interactions between the endocannabinoid and orexin systems. Cannabinoid and orexin receptors have been shown to form heterodimers in agreement with the overlapping distribution of both receptors in several brain areas, and the activation of common intracellular signaling pathways, such as the MAP kinase cascade. The activation of orexin receptors induces the synthesis of the endocannabinoid 2-arachidonoyl glycerol suggesting that the endocannabinoid system participates in some physiological functions of orexins. Indeed, functional interactions between these two systems have been demonstrated in several behavioral responses including nociception, reward and food intake. The present review is focused on the latest developments in cannabinoid-orexin cross-modulation and the implications of this interesting interaction.


Cannabinoid; Feeding; Heterodimers; Nociception; Orexin; Reward


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