{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:18:06Z","timestamp":1757611086111,"version":"3.44.0"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,9,5]]},"abstract":"<jats:p>\n            Despite effective antiretroviral therapy (ART), people with HIV (PWH) experience persistent inflammation and metabolic dysfunction, increasing their risk for non-AIDS comorbidities. Accordingly, we evaluated the effects of long-term\/low-dose \u0394\n            <jats:sup>9<\/jats:sup>\n            -tetrahydrocannabinol (THC) supplementation in simian immunodeficiency virus (SIV)\u2013infected, ART-treated rhesus macaques (RMs). THC significantly increased plasma\/jejunum serotonin and indole-3-propionate, enhancing gut-brain communication through up-regulation of serotonin receptors (HTR4\/HTR7) and aryl hydrocarbon receptor (Ahr) signaling via a cannabinoid receptor (CBR)-2\u2013mediated mechanism. Furthermore, THC enriched cholesterol-metabolizing\n            <jats:italic toggle=\"yes\">Oscillibacter<\/jats:italic>\n            and reduced plasma cholesterol and toxic secondary bile acids (SBAs), thus improving cholesterol and SBA homeostasis. Furthermore, THC increased \u03b2-hydroxybutyrate (BHB) levels via a CBR1-mediated mechanism, suggesting enhanced hepatic fatty acid oxidation for metabolic and cardiovascular health. THC restored ART\/SIV-induced elevation of pro-inflammatory and cardiotoxic long-chain acylcholines to preinfection levels. THC-treated RMs maintained viral suppression despite reduced plasma ART levels, suggesting diminished ART-related toxicity. Our findings demonstrate phytocannabinoids to be a safe adjunct therapy alongside ART to mitigate chronic inflammation and metabolic dysfunction in PWH.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adw4021","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:58:46Z","timestamp":1756922326000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-5208","authenticated-orcid":true,"given":"Lakmini S.","family":"Premadasa","sequence":"first","affiliation":[{"name":"Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX 78227, 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