{"doi":"10.1126/sciadv.adw4021","title":"Supplementing HIV-ART with cannabinoids increases serotonin, BHB, and Ahr signaling while reducing secondary bile acids and acylcholines","abstract":"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 Δ 9 -tetrahydrocannabinol (THC) supplementation in simian immunodeficiency virus (SIV)–infected, 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–mediated mechanism. Furthermore, THC enriched cholesterol-metabolizing Oscillibacter and reduced plasma cholesterol and toxic secondary bile acids (SBAs), thus improving cholesterol and SBA homeostasis. Furthermore, THC increased β-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.","journal":"Science Advances","year":2025,"id":574206,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1481642,"name":"Luis Romero","orcid":"0009-0005-4754-0287","position":1,"is_corresponding":false},{"id":296006,"name":"Mahesh Mohan","orcid":"0000-0003-4360-3277","position":2,"is_corresponding":false},{"id":761022,"name":"Lakmini S. Premadasa","orcid":"0000-0001-7435-5208","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"40901952","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}