{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:30:11Z","timestamp":1766719811846,"version":"3.40.4"},"reference-count":32,"publisher":"American Veterinary Medical Association (AVMA)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine the effect of premedication followed by isoflurane (ISO) versus sevoflurane (SEVO), length of general anesthesia (GA), and the amount of IV fluid administered on plasma endocannabinoid arachidonoyl ethanolamide (anandamide; AEA) concentrations in dogs undergoing GA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study was an analysis of samples collected during a previously designed prospective, randomized, single-blinded experimental study involving 21 client-owned dogs undergoing GA. Samples were collected from March through October 2021. Dogs were randomized to ISO or SEVO as the inhalant anesthetic. Blood samples collected before and after GA were used to measure plasma AEA concentrations using HPLC-MS-MS. Data included signalment, length of GA (minutes), surgery performed, fluid volume administered (milliliters per kilogram), and treatment with NSAIDs or steroids. Statistical analyses included power analysis, normality testing, and adjusted linear mixed models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>Plasma AEA concentrations significantly decreased after GA in both groups. Least squares mean AEA concentration decreased from 29 to 12.3 ng\/mL in the ISO group and from 26.6 to 11.1 ng\/mL in the SEVO group. There were no significant differences between groups or associations with anesthesia duration, fluid volume, surgery, or NSAID\/steroid use.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Plasma AEA concentrations were significantly reduced after GA in both the ISO and SEVO groups. This reduction may be influenced by other anesthesia agents, such as dexmedetomidine, hydromorphone, and propofol.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>This study is the first to highlight a potential interaction between premedication, GA, and endocannabinoid signaling. Further research is needed to explore these findings and their implications for pain management and neuroprotection.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.11.0366","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T14:00:02Z","timestamp":1740664802000},"source":"Crossref","is-referenced-by-count":1,"title":["Premedication and general anesthetic agents decrease plasma concentration of the endocannabinoid anandamide in dogs"],"prefix":"10.2460","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5773-4246","authenticated-orcid":true,"given":"Andrew","family":"Chua","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen A.","family":"McMichael","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0124-4926","authenticated-orcid":true,"given":"Tom","family":"Jukier","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-3991","authenticated-orcid":true,"given":"Robert D.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Chu Ellan","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2276-9676","authenticated-orcid":true,"given":"Hedie Almagro","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"7","key":"B1","series-title":"Biol Psychiatry","first-page":"516","article-title":"An introduction to the endogenous cannabinoid system","volume":"79","author":"Lu HC","year":"2016","unstructured":"Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 2016;79(7):516\u2013525. doi:10.1016\/j.biopsych.2015.07.028"},{"issue":"1","key":"B2","series-title":"J Psychoactive Drugs","first-page":"23","article-title":"The religious and medicinal uses of Cannabis in China, India and Tibet","volume":"13","author":"Touw M","year":"1981","unstructured":"Touw M. The religious and medicinal uses of Cannabis in China, India and Tibet. J Psychoactive Drugs. 1981;13(1):23\u201334. doi:10.1080\/02791072.1981.10471447"},{"issue":"8","key":"B3","series-title":"J Am Chem Soc","first-page":"1646","article-title":"Isolation, structure, and partial synthesis of an active constituent of hashish","volume":"86","author":"Gaoni Y","year":"1964","unstructured":"Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. 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Nature. 1993;365(6441):61\u201365. doi:10.1038\/365061a0"},{"issue":"3","key":"B6","series-title":"Neuroscience","first-page":"969","article-title":"Cannabinoid CB1 receptors are localized primarily on cholecystokinin-containing GABAergic interneurons in the rat hippocampal formation","volume":"93","author":"Tsou K","year":"1999","unstructured":"Tsou K, Mackie K, Sa\u00f1udo-Pe\u00f1a MC, Walker JM. Cannabinoid CB1 receptors are localized primarily on cholecystokinin-containing GABAergic interneurons in the rat hippocampal formation. Neuroscience. 1999;93(3):969\u2013975. doi:10.1016\/S0306-4522(99)00086-X"},{"issue":"11","key":"B7","series-title":"J Neurosci","first-page":"4544","article-title":"Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons","volume":"19","author":"Katona I","year":"1999","unstructured":"Katona I, Sperl\u00e1gh B, S\u00edk A, et al. 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