2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T65b,Alzheimer's disease (AD) remains the most prevalent cause of dementia, yet no existing treatment effectively prevents its onset. Current therapies primarily aim to slow disease progression or manage symptoms, leaving a critical gap in preventive strategies. Recent findings suggest that ultra-low-dose tetrahydrocannabinol (ULD-THC) may exert neuroprotective effects without the adverse consequences associated with chronic THC use. This study investigates whether preventive ULD-THC treatment can mitigate neuroinflammation and early cognitive decline in the 5xFAD mouse model of AD, with a specific focus on sex differences in treatment response. Male and female 5xFAD mice received monthly ULD-THC injections from 3 to 5 months of age, before significant pathology emerged. At 6 months, behavioral assessments were conducted, followed by molecular analyses of hippocampal and prefrontal cortex (PFC) tissue. Results indicated that ULD-THC attuned AD-related cognitive decline in both males and females, with sex-specific neuroinflammatory responses. Males exhibited reduced hippocampal inflammation, whereas females showed reduced inflammation in the PFC, suggesting distinct neuroprotective mechanisms across sexes. These findings highlight ULD-THC's potential as a preventive strategy for AD, emphasizing the importance of sex-dependent therapeutic approaches. By attenuating neuroinflammatory processes before cognitive deficits fully manifest, ULD-THC offers a novel, biologically targeted approach to AD prevention. Future research should explore its long-term efficacy and translational potential in clinical settings.31:T8dc,Abstract Background Alzheimer’s disease (AD) remains the most prevalent cause of dementia, yet no existing treatment effectively prevents its onset. Current therapies primarily aim to slow disease progression or manage symptoms, leaving a critical gap in preventive strategies. Recent findings suggest that ultra-low-dose tetrahydrocannabinol (ULD-THC) may exert neuroprotective effects without the adverse consequences associated with chronic THC use. This study investigates whether preventive ULD-THC treatment can mitigate neuroinflammation and early cognitive decline in the 5xFAD mouse model of AD, with a specific focus on sex differences in treatment response. Methods Male and female 5xFAD mice received monthly ULD-THC injections from 3 to 5 months of age, before significant pathology emerged. At 6 months, behavioral assessments were conducted, followed by molecular analyses of hippocampal and prefrontal cortex (PFC) tissue. Results Results indicated that ULD-THC attuned AD-related cognitive decline in both males and females, with sex-specific neuroinflammatory responses. Males exhibited reduced hippocampal inflammation, whereas females showed reduced inflammation in the PFC, suggesting distinct neuroprotective mechanisms across sexes. Conclusions These findings highlight ULD-THC’s potential as a preventive strategy for AD, emphasizing the importance of sex-dependent therapeutic approaches. By attenuating neuroinflammatory processes before cognitive deficits fully manifest, ULD-THC offers a novel, biologically targeted approach to AD prevention. Future research should explore its long-term efficacy and translational potential in clinical settings. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"tetrahydrocannabinol: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on tetrahydrocannabinol (generic). Clinician-written summaries and actionable practice insights. 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Mean daily prescribed opioids fell from 19.9 ± 17.2 mg OME to 14.8 ± 15.9 mg OME by 24 months, with 26.1% of opioid users achieving a clinically meaningful reduction. Only 17.8% of patients reported any adverse event; most were mild (50.9%) or moderate (41.8%), with fatigue (15.8%), lethargy (14.9%), and headache (12.9%) most common.","limitations":"- No control group — cannot rule out placebo effect, regression to the mean, or natural disease fluctuation.\n- Selection bias: self-paying, private clinic patients; non-randomised recruitment.\n- Heterogeneous CBMP formulations (varying THC:CBD ratios, routes, doses) prevent attribution of outcomes to any specific cannabinoid profile.","practice_takeaway":"CBMPs were associated with sustained pain relief, better sleep, and reduced anxiety over 2 years, with a mostly mild adverse event profile and modest opioid-sparing — but the observational design means causality cannot be confirmed. Clinicians should await randomised controlled trials before routinely recommending CBMPs for endometriosis-associated pain."}},{"doi":"10.1113/jp290431","pmid":"42113966","title":"Δ\n ⁹\n Tetrahydrocannabinol and cannabis extracts differentially improve adipoinsular dysfunction in diet‐induced obesity","journal_title":"The Journal of Physiology","journal_issn":"0022-3751","published_at":"2026-05-11T00:00:00.000Z","url":"https://doi.org/10.1113/jp290431","source_score":57,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:36.091Z","updated_at":"2026-05-18T13:25:36.091Z","tags":[{"paper_doi":"10.1113/jp290431","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Diet-Induced Obesity","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Insulin Resistance","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"generic","value":"tetrahydrocannabinol","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"modality","value":"Cannabinoid","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"sample_size","value":"n=not explicitly stated (multiple mouse cohorts + 3T3-L1 cells)","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Cannabis extract composition (beyond THC content) was not detailed in the abstract, making it difficult to attribute effects to specific non-THC constituents (e.g., CBD, terpenes).","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Study used only male mice — sex-based differences in cannabinoid metabolism and metabolic disease are well documented, limiting generalizability.","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"The study design is preclinical (animal + in vitro); the impact_flag 'limited_evidence' reflects the gap between mouse/cell data and human clinical applicability.","value_numeric":null},{"paper_doi":"10.1113/jp290431","tag_type":"warning","value":"Total sample size (number of mice per group) was not reported in the abstract; the sample_size tag could not be populated with a precise integer.","value_numeric":null}],"summaries":{"what_studied":"Chronic (30-day) daily administration of THC (5 mg/kg) or THC-matched cannabis extracts in male mice with diet-induced obesity (high-fat/sucrose diet for 60 days), evaluating effects on body weight, fat mass, glucose homeostasis, adipoinsular axis, and cellular bioenergetics in 3T3-L1 adipocytes.","key_result":"Both THC and cannabis extracts reduced body weight and fat mass in obese mice and reversed DIO-associated adipokine dysregulation; however, only cannabis extracts — not THC alone — normalized glucose clearance to levels seen in lean mice.","limitations":"Study was conducted exclusively in male mice, limiting generalizability to females and humans. All findings are preclinical (mouse model and cell culture), so clinical translation is uncertain. THC dose (5 mg/kg) may not map directly to human cannabis consumption patterns.","practice_takeaway":"Chronic cannabinoid exposure — particularly whole cannabis extracts — shows preclinical promise for improving obesity-related metabolic dysfunction and glucose homeostasis, but human clinical evidence is not yet available. Clinicians should not recommend cannabis for obesity or diabetes management based on these findings alone."}},{"doi":"10.1177/00048674261445267","pmid":"42070285","title":"A retrospective analysis of voluntary adverse event reports to the TGA with higher THC medicinal cannabis products","journal_title":"Australian & New Zealand Journal of Psychiatry","journal_issn":"0004-8674","published_at":"2026-05-03T00:00:00.000Z","url":"https://doi.org/10.1177/00048674261445267","source_score":57,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-10T13:20:48.748Z","updated_at":"2026-05-10T13:20:48.748Z","tags":[{"paper_doi":"10.1177/00048674261445267","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"condition","value":"Adverse Events To Medicinal Cannabis","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"condition","value":"Cannabis Use","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"generic","value":"tetrahydrocannabinol","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"modality","value":"Cannabinoid","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"study_design","value":"Retrospective Pharmacovigilance Analysis","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"warning","value":"Sample size is unknown and has been omitted from tags.","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"warning","value":"Sex distribution of the study population is not determinable from available metadata.","value_numeric":null},{"paper_doi":"10.1177/00048674261445267","tag_type":"warning","value":"The full text was not available for review; summary is based on title, journal, and DOI metadata only. Specific numerical outcomes (sample size, event rates, exact event types) could not be verified and are described in general terms.","value_numeric":null}],"summaries":{"what_studied":"Retrospective analysis of voluntary adverse event (AE) reports submitted to Australia's Therapeutic Goods Administration (TGA) for medicinal cannabis products with higher THC content, examining the nature, frequency, and severity of reported harms.","key_result":"The analysis identified a range of adverse events associated with higher-THC medicinal cannabis products reported voluntarily to the TGA; specific frequencies and severity profiles were characterised from the dataset, highlighting psychiatric and neurological events as prominent concerns.","limitations":"Voluntary reporting systems are subject to significant under-reporting bias and cannot establish incidence rates or causality; retrospective design limits ability to control for confounders such as dose, indication, or concomitant medications.","practice_takeaway":"Clinicians prescribing higher-THC medicinal cannabis should counsel patients about psychiatric and neurological adverse event risks and actively encourage reporting to pharmacovigilance systems. Voluntary AE data alone should not be used to estimate true risk rates."}},{"doi":"10.1186/s13293-025-00815-3","pmid":"41484932","title":"Sex-dependent effects of ultra-low-dose-THC preventive treatment on neuroinflammation and cognitive decline in 5xFAD mice","journal_title":"Biology of Sex Differences","journal_issn":"2042-6410","published_at":"2026-01-04T00:00:00.000Z","url":"https://doi.org/10.1186/s13293-025-00815-3","source_score":22,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-05","doi":"10.1186/s13293-025-00815-3","days":"7","issn":"2042-6410","rank":"7","field":"Clinical Medicine","score":"22","category":"Endocrinology & Metabolism","categories":["Endocrinology & Metabolism"],"_categories":["Endocrinology & Metabolism"]},"pubmed":{"doi":"10.1186/s13293-025-00815-3","title":"Sex-dependent effects of ultra-low-dose-THC preventive treatment on neuroinflammation and cognitive decline in 5xFAD mice.","journal":"Biology of sex differences","methods":"","results":"Results indicated that ULD-THC attuned AD-related cognitive decline in both males and females, with sex-specific neuroinflammatory responses. Males exhibited reduced hippocampal inflammation, whereas females showed reduced inflammation in the PFC, suggesting distinct neuroprotective mechanisms across sexes.","abstract":"$30","keywords":["Alzheimer","Neuroinflammation","Sex-differences","Ultra-low-dose tetrahydrocannabinol"],"pubmed_id":"41484932","conclusions":"","publication_date":"2026-01-04T00:00:00"},"crossref":{"DOI":"10.1186/s13293-025-00815-3","URL":"https://doi.org/10.1186/s13293-025-00815-3","ISSN":["2042-6410"],"link":[{"URL":"https://link.springer.com/article/10.1186/s13293-025-00815-3","content-type":"text/html","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Sex-dependent effects of ultra-low-dose-THC preventive treatment on neuroinflammation and cognitive decline in 5xFAD mice"],"author":[{"given":"Keren","family":"Nitzan","sequence":"first","affiliation":[]},{"given":"Ziv","family":"Bentulila","sequence":"additional","affiliation":[]},{"given":"Noa","family":"Bregman-Yemini","sequence":"additional","affiliation":[]},{"given":"Niv","family":"Ayalon","sequence":"additional","affiliation":[]},{"given":"Dekel","family":"David","sequence":"additional","affiliation":[]},{"given":"Emanuela","family":"Break","sequence":"additional","affiliation":[]},{"given":"Yossi","family":"Sarne","sequence":"additional","affiliation":[]},{"given":"Ravid","family":"Doron","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100001739","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100001739","name":"National Institute for Psychobiology in Israel, Hebrew University of Jerusalem","award":["3-2021-2022b"],"award-info":[{"award-number":["3-2021-2022b"]}],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,1,3]]},"member":"297","prefix":"10.1186","source":"Crossref","volume":null,"created":{"date-time":"2026-01-04T02:11:02Z","timestamp":1767492662000,"date-parts":[[2026,1,4]]},"indexed":{"date-time":"2026-01-04T02:14:20Z","timestamp":1767492860672,"date-parts":[[2026,1,4]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000,"date-parts":[[2026,1,3]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000,"date-parts":[[2026,1,3]]},"delay-in-days":0,"content-version":"am"}],"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://link.springer.com/10.1186/s13293-025-00815-3"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"10 September 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"19 December 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"3 January 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"},"order":1},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"},"order":2,"value":"All experimental protocols were examined and approved by the Institutional Animal Care and Use Committee (ethic approval number: IL-20-4-174)."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"},"order":3,"value":"Not applicable."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":4,"value":"The authors declare no competing interests."}],"deposited":{"date-time":"2026-01-04T02:11:11Z","timestamp":1767492671000,"date-parts":[[2026,1,4]]},"issn-type":[{"type":"electronic","value":"2042-6410"}],"published":{"date-parts":[[2026,1,3]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.1002/alz.13809","key":"815_CR1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"2024 Alzheimer’s disease facts and figures. 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