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However, the underlying mechanisms have not been completely elucidated, which is critical to understanding their utility. The orexin\/hypocretin (OH) system of the lateral hypothalamus (LHA) has known anatomical, biochemical, and physiological interactions with the endocannabinoid system, and has an established role in promoting appetitive behavior; yet, it is still unknown if the OH system mediates food intake following cannabinoid administration. Herein, we validated an oral method of cannabinoid receptor agonist, CP55940, administration via gelatin\u2010based edibles, showing that voluntarily consumed cannabinoid\u2010containing edibles produce acute hyperphagia via an increase in meal number in male rats. Following cannabinoid administration, rats displayed an upregulation in the immediate early gene c\u2010Fos in OH neurons compared to vehicle\u2010treated animals. We further employed a within\u2010subjects design to investigate whether orexin\u20101 (OX1) receptor signaling was necessary for cannabinoid\u2010induced hyperphagia by coadministering a subeffective dose of an OX1 receptor antagonist, SB334867, with the cannabinoid\u2010containing edible. Data were collected from metabolic monitoring cages, simultaneously capturing chow intake, locomotor activity, and metabolic variables. Results showed that the OX1 receptor antagonist blocked cannabinoid\u2010induced hyperphagia and the transient increase in locomotor activity following cannabinoid administration. Furthermore, both the edible cannabinoid receptor agonist and the OX1 receptor antagonist individually reduced energy expenditure several hours following administration. Taken together, we conclude that the OX1 receptor is required for the hyperphagic response to exogenous cannabinoid administration.<\/jats:p>","DOI":"10.1002\/prp2.70171","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T13:19:37Z","timestamp":1757078377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabinoid\u2010Induced Hyperphagia is Mediated by Increased Meal Frequency and the Orexin\u20101 Receptor in Male Rats"],"prefix":"10.1002","volume":"13","author":[{"given":"Magen N.","family":"Lord","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences University of Georgia  Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace C.","family":"Madu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Georgia  Athens Georgia 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