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Three\u2010month\u2010old female Wistar rats were randomly assigned to four experimental groups: SHAM\u2010Veh (Vehicle), OVX\u2010Veh, OVX\u2010E2 (estradiol), and OVX\u2010CBD. Animals underwent either bilateral ovariectomy or sham surgery. Following a three\u2010week recovery period, rats received daily subcutaneous injections of CBD (10\u2009mg\/kg), estradiol (10\u2009\u03bcg\/kg), or vehicle for 21 consecutive days. Behavioral assessments included object recognition and fear\u2010motivated memory tests. Twenty\u2010four hours after the final treatment, animals were euthanized for neurochemical and molecular analyses. Levels of the endocannabinoids anandamide (AEA) and 2\u2010arachidonoylglycerol (2\u2010AG) were measured using high\u2010performance liquid chromatography. Gene expression of cannabinoid receptors CB1 and CB2, as well as enzymes involved in the synthesis and degradation of endocannabinoids (NAPE\u2010PLD, DAGL\u2010A, FAAH, and MGLL), was evaluated in the hippocampus by RT\u2010qPCR. The results demonstrated that CBD treatment produced memory improvements in the object recognition task comparable to those observed with estradiol. Ovariectomy\u2010induced impairments in fear\u2010motivated memory were completely reversed by both CBD and estradiol treatments. Additionally, CBD reduced the expression of FAAH and MGLL, resulting in increased hippocampal levels of AEA and 2\u2010AG, effects similar to those observed with hormone therapy. Estradiol also increased NAPE\u2010PLD expression, contributing to elevated AEA levels. Overall, the findings suggest that CBD exerts a protective effect on memory comparable to standard estrogen therapy, supporting its therapeutic potential for menopause\u2010related cognitive impairments.<\/jats:p>","DOI":"10.1111\/jne.70234","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T02:58:52Z","timestamp":1784602732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of cannabidiol in comparison to hormonal therapy on estrogen decline\u2010induced memory impairments and endocannabinoid system in rats"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1579-1856","authenticated-orcid":false,"given":"Fernanda Borsatto","family":"Caruso","sequence":"first","affiliation":[{"name":"Laboratory of Memory Dysfunctions, Department of Physiology, Institute for Basic Health Sciences Federal University of Rio Grande do Sul  Porto Alegre 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