{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:00:03Z","timestamp":1782849603270,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T00:00:00Z","timestamp":1661040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open University of Israel","award":["2-2021-2022"],"award-info":[{"award-number":["2-2021-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common form of dementia, but there is still no available treatment. \u03949-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg\/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus. We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC. The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset.<\/jats:p>","DOI":"10.3390\/ijms23169449","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["An Ultra-Low Dose of \u22069-Tetrahydrocannabinol Alleviates Alzheimer\u2019s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-9431","authenticated-orcid":false,"given":"Keren","family":"Nitzan","sequence":"first","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Ellenbogen","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-6800","authenticated-orcid":false,"given":"Ziv","family":"Bentulila","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-9145","authenticated-orcid":false,"given":"Dekel","family":"David","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motty","family":"Franko","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela P.","family":"Break","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Zoharetz","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon","family":"Shamir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Technion\u2013Israel Institute of Technology, Haifa 3200003, Israel"},{"name":"Mazor Mental Health Center, Akko 2423314, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosef","family":"Sarne","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6523-9886","authenticated-orcid":false,"given":"Ravid","family":"Doron","sequence":"additional","affiliation":[{"name":"Department of Education and Psychology, The Open University, Ra\u2019anana 4353701, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.1132814","article-title":"A Century of Alzheimer\u2019s Disease","volume":"314","author":"Goedert","year":"2006","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jalz.2010.04.006","article-title":"Alzheimer\u2019s Disease, a Multifactorial Disorder Seeking Multitherapies","volume":"6","author":"Iqbal","year":"2010","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/ddr.21652","article-title":"Alzheimer\u2019s Disease: A Need for Personalized Therapeutic Approaches","volume":"81","author":"Frenkel","year":"2020","journal-title":"Drug Dev. 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