British Journal of Pharmacology最新文献

{"title":"Correction to An antisense oligonucleotide targeting the heat-shock protein HSPB5 as an innovative therapeutic approach in pulmonary fibrosis","authors":"","doi":"10.1111/bph.70197","DOIUrl":"10.1111/bph.70197","url":null,"abstract":"<p>\u0000 <span>Boutanquoi, P.-M.</span>, <span>Pommerolle, L.</span>, <span>Dondaine, L.</span>, <span>Tanguy, J.</span>, <span>Bellaye, P.-S.</span>, <span>Biziorek, L.</span>, <span>Gautier-Isola, M.</span>, <span>Mari, B.</span>, <span>Masnikov, D.</span>, <span>Rocchi, P.</span>, <span>Finetti, P.</span>, <span>Korczak, P.</span>, <span>Vialet, B.</span>, <span>Barthelemy, P.</span>, <span>Garrido, C.</span>, <span>Bonniaud, P.</span>, <span>Burgy, O.</span>, and <span>Goirand, F.</span> <span>An antisense oligonucleotide targeting the heat-shock protein HSPB5 as an innovative therapeutic approach in pulmonary fibrosis</span>. <i>British Journal of Pharmacology</i> <span>182</span>, no. <span>12</span> (<span>2025</span>): <span>2713</span>–<span>2729</span>, https://doi.org/10.1111/bph.17470</p><p>The published article's Conflict of Interest statement did not include one author's potential competing interest. The correct Conflict of Interest statement is as follows:</p><p><b>CONFLICT OF INTEREST STATEMENT</b></p><p>P. Rocchi is a cofounder of SilonTx (https://silontx.com), a biotech company started in April 2024 focusing on precision medicine and nucleic acid therapeutics. The other authors declare no competing interests.</p><p>We apologize for this error.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 21","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.70197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology.","authors":"Lucas Wittenkeller, Gary Gudelsky, T John Winhusen, Davide Amato","doi":"10.1111/bph.70181","DOIUrl":"https://doi.org/10.1111/bph.70181","url":null,"abstract":"<p><p>Psychedelics have garnered great attention in recent years as treatments for major depressive disorder (MDD) and treatment-resistant depression because of their ability to alter consciousness and afflicted cognitive processes with lasting effects. We aimed to characterise how psychedelics are currently being investigated to treat substance use disorders (SUDs). Additionally, we aimed to summarise the available literature on the dopaminergic consequences of classic psychedelics in the nucleus accumbens (NAc), a foundational component of SUDs, to understand how psychedelics may be therapeutically relevant for SUDs from a neurobiological perspective. Two scoping review approaches adhering to PRISMA-SCR guidelines were conducted. The first screened for ongoing clinical trials utilising psychedelics for SUD treatment registered at ClinicalTrials.gov. The second screened for in vivo microdialysis studies measuring psychedelic-induced changes in extracellular NAc dopamine in rats, found using PubMed, SCOPUS or Google Scholar. Thirty-four unique clinical trials were identified targeting alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioid use disorders and mostly consisting of open-label trials lacking placebo-treated controls. The most common SUD investigated was alcohol use disorder (AUD). Following stringent exclusion criteria, four publications were identified that measured extracellular dopamine in the NAc following systemic administration of psilocybin or 3,4-methylenedioxymethamphetamine (MDMA). A sustained mild increase of dopamine was observed that was unique to high-dose psilocybin. In addition to known therapeutic mechanisms of psychedelics, findings herein suggest that psilocybin may support dopamine homeostasis through restoration of tonic dopamine levels.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methanobactin rapidly facilitates biliary copper excretion in a Wilson disease rat model visualised by ⁶⁴Cu PET/MRI.","authors":"Emilie Munk Lynderup, Mikkel Holm Vendelbo, Frederik Teicher Kirk, Karina Højrup Vase, Aage Kristian Olsen Alstrup, Tamara Rieder, Alan A DiSpirito, Jeremy D Semrau, Tea Lund Laursen, Peter Ott, Hans Zischka, Thomas Damgaard Sandahl","doi":"10.1111/bph.70099","DOIUrl":"https://doi.org/10.1111/bph.70099","url":null,"abstract":"<p><strong>Background and purpose: </strong>Methanobactins are peptides with high copper affinity and potential to treat Wilson disease. We examined how two methanobactins (ARBM101 and MB-OB3b) affected copper handling in the LPP Atp7b^-/- Wilson disease rat model, compared to penicillamine or saline, by ⁶⁴Cu positron emission tomography/magnetic resonance imaging. Heterozygotes served as controls.</p><p><strong>Experimental approach: </strong>⁶⁴Cu was administered i.v. to 19 LPP and four control rats. A baseline scan was performed 1 h later. LPP rats received one dose of saline, penicillamine, MB-OB3b or ARBM101 i.p. (t = 100 min), followed by a 90-min scan and a final scan at t = 24 h. Controls followed identical procedures without intervention. ⁶⁴Cu levels were evaluated as % injected dose (%ID) in the liver, kidney and 'abdominal-pelvic region' (intestines and other non-hepatic, non-renal organs).</p><p><strong>Key results: </strong>At baseline, hepatic %ID was ≈50% higher in LPP rats than in controls. Intraintestinal ⁶⁴Cu activity, indicating biliary excretion, was present in controls and absent in LPP rats. After methanobactin injection (but not saline or penicillamine), ⁶⁴Cu appeared in the small intestines of LPP rats within 10-15 min. Hepatic %ID increased over 24 h in saline-, penicillamine- and MB-OB3b-injected rats but decreased in control rats. ARBM101 almost normalised hepatic ⁶⁴Cu at 24 h.</p><p><strong>Conclusions and implications: </strong>A single i.p. methanobactin dose restored biliary copper excretion in LPP rats. The effect was more pronounced with ARBM101 than with MB-OB3b. Non-ATP7B transporters must be involved because ATP7B is absent in LPP rats. Methanobactin may have therapeutic potential in Wilson disease.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap: Extracellular matrix-based strategies for peripheral nerve regeneration and neuropathic pain management.","authors":"Siddharth Raj, Abhijeet R Joshi","doi":"10.1111/bph.70183","DOIUrl":"https://doi.org/10.1111/bph.70183","url":null,"abstract":"<p><p>Peripheral neuropathic pain, arising from peripheral nerve injuries, remains a significant clinical challenge because of complex pathophysiology and limited treatment options. Conventional treatments primarily provide symptomatic relief, failing to address underlying nerve damage. The extracellular matrix (ECM) plays a vital role in nerve regeneration by offering structural support and biochemical signals that regulate Schwann cell behaviour, axonal growth and microenvironment remodelling. This review critically examines ECM-based scaffold strategies, focussing on natural proteins such as collagen, laminin and fibronectin and their role in promoting functional nerve recovery. In addition, the role of emerging molecular regulators, including Piezo1 mechanosensitive channels and nuclear transport proteins, is examined for their ability to mediate mechanotransduction and gene regulatory mechanisms critical for nerve regeneration and pain modulation. By integrating biomaterial engineering, mechanical signalling pathways and gene-targeted strategies, this review outlines promising regenerative approaches aimed at restoring nerve function and alleviating chronic pain. These insights may guide the development of next-generation therapies for peripheral nerve repair.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network-based precision medicine and systems pharmacology.","authors":"Arvind K Pandey, Susan Dina Ghiassian, Joseph Loscalzo","doi":"10.1111/bph.70184","DOIUrl":"https://doi.org/10.1111/bph.70184","url":null,"abstract":"<p><p>The growth in detailed multi-omic profiling has created new opportunities to tailor clinical care and therapy to patient-level variations in disease phenotype. However, efforts towards precision medicine and personalised therapeutics are hampered by limitations in identifying biologically relevant signals that correlate with and underlie disease activity and therapeutic response from these growing arrays of data. These complexities are accentuated further when attempting to translate the new insights in disease pathobiology into new drug targets for treatment. Additionally, understanding how best to reposition existing drugs in the context of new data on disease pathogenesis remains a challenge. Network medicine provides one approach to comprehend these large data sets and identify better the key molecular and phenotypic signals that can function as disease and treatment biomarkers and that can be targeted for therapy. In this review, we discuss basic concepts in the application of network science to biological systems and then build on these concepts to discuss network-based approaches for identifying novel disease biomarkers, elucidating new drug targets and repositioning existing drugs for new indications.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased ATP production and P-glycoprotein activity underlie the marked changes in blood-brain barrier transport of drugs in a mouse model of amyotrophic lateral sclerosis.","authors":"Yijun Pan, Alanna G Spiteri, Pranav Runwal, Jiaqi Sun, Dana S Hutchinson, Yoshiteru Kagawa, Bradley J Turner, Cheng Huang, Anup D Shah, Ralf B Schittenhelm, Joseph A Nicolazzo","doi":"10.1111/bph.70147","DOIUrl":"https://doi.org/10.1111/bph.70147","url":null,"abstract":"<p><strong>Background and purpose: </strong>Patients with amyotrophic lateral sclerosis (ALS) are prescribed many medications for symptomatic relief. However, how potential alterations to the blood-brain barrier (BBB) affect the brain exposure of drugs in ALS remains under-investigated.</p><p><strong>Experimental approach: </strong>We used high-dimensional proteomic analysis, cellular metabolism, and mitochondrial functional assays to characterise isolated brain microvascular endothelial cells (BMECs) from wildtype and SOD1^G93A transgenic mice, a mouse model of familial ALS, at a late-symptomatic age (P115-120), together with a transcardiac brain perfusion technique to assess BBB function in situ.</p><p><strong>Key results: </strong>The BBB of the SOD1^G93A transgenic (TG) mice was significantly altered, including a 1.3-fold decrease in apparent brain microvascular volume, and decreased BBB transport of ³H-diazepam (1.4-fold) and ³H-2-deoxy-D-glucose (1.2-fold). BMEC proteomic analysis revealed multiple changes in TG mice including altered transmembrane activity, metabolism, and mitochondrial function, as revealed by gene set enrichment analysis, alongside altered glucose transporter (Glut1) abundance. These proteomic findings supported the identified increase in mitochondrial basal/ATP-linked respiration, mitochondrial action potential, ATP production, and intracellular ATP levels in SOD1^G93A mouse BMECs. The BBB transport of ³H-digoxin, a specific ATP-binding cassette efflux P-glycoprotein (P-gp) substrate, was reduced by 11.0% in SOD1^G93A mice. This was confirmed by a 46.7% reduction in BMEC uptake of ³H-digoxin, an observation that was reversed by resolving the hypermetabolic state of SOD1^G93A BMECs.</p><p><strong>Conclusion and implications: </strong>These findings open possible therapeutic avenues that could be exploited to overcome P-gp-mediated CNS drug resistance in ALS.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating G6PD/PGD to overcome FSP1/DHODH-mediated ferroptosis defence: A novel oridonin derivative suppresses liver cancer.","authors":"Chenhui Ma, Li Han, Hong Yao, Wenxuan Zhao, Feihong Chen, Xiuyuan Wu, Guoqi Li, Ruimin Huang, Cheng Heng Pang, Zheying Zhu, Jinyi Xu, Guoyu Pan","doi":"10.1111/bph.70160","DOIUrl":"https://doi.org/10.1111/bph.70160","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC), a globally prevalent malignancy with high mortality rates, presents an unmet need for innovative effective therapies.</p><p><strong>Purpose: </strong>This study aimed to explore the antitumour potential of compound XD, a novel oridonin derivative, on HCC and its underlying mechanism.</p><p><strong>Experimental approach: </strong>The antitumour effects of compound XD were investigated in several HCC cells lines and mice models. The mechanism of XD was investigated using FACS, qPCR, WB, ELISA, IHC, siRNA and plasmid transfection.</p><p><strong>Key results: </strong>Compound XD demonstrated potent inhibitory effects, surpassing sorafenib with a maximum of 10-fold lower IC₅₀ values against HCC cell lines. Its anticancer activities were ferroptosis dependent, which could be attenuated by ferroptosis inhibitors including deferoxamine, ferrostatin-1 and N-acetyl-cysteine. Unlike sorafenib, XD decreased two pivotal regulator FSP1 and DHODH to induce ferroptosis, while their overexpression partially mitigated XD-induced cytotoxicity and lipid peroxidation. In addition, XD treatment decreased cellular NADPH levels and inhibited the expression of G6PD and PGD in NADPH generation. Overexpression of G6PD or PGD reversed FSP1 and DHODH down-regulation, rescuing the ferroptosis induced by XD. Bioinformation analysis indicated the significant up-regulation of G6PD and PGD in clinical HCC patients and was positively correlated with cancer stages. Molecular docking and CETSA assay confirmed the binding capacity of XD with G6PD and PGD protein. Finally, XD dose-dependently inhibited liver tumour growth and induced ferroptosis-related markers in mice.</p><p><strong>Conclusion and implications: </strong>This study suggests XD as a potential ferroptosis inducer and the potential role of G6PD/PGD/FSP1/DHODH axis in governing ferroptosis sensitivity in HCC.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel peptide-fentanyl conjugate with μ-opioid and neuropeptide FF receptor agonism produces antinociception with limited side effects in male mice.","authors":"Ning Li, Mengna Zhang, Biao Xu, Zhenyun Yang, Hengpei Zhao, Feiyun Gao, Kangtai Xu, Wenqi Yan, Nan Zhang, Quan Fang","doi":"10.1111/bph.70178","DOIUrl":"https://doi.org/10.1111/bph.70178","url":null,"abstract":"<p><strong>Background and purpose: </strong>The opioid crisis caused by the proliferation of fentanyl-related drugs has intensified concerns about the utilisation of opioid analgesics. Herein, a novel peptide-drug conjugate FENPFF01, incorporating the neuropeptide FF (NPFF) and fentanyl pharmacophores, was synthesised and pharmacologically characterised.</p><p><strong>Experimental approach: </strong>The agonist activities of FENPFF01 at opioid and NPFF receptors were characterised in in vitro functional assays. Antinociceptive effects and underlying pharmacological mechanisms of FENPFF01 were assessed in multiple mouse pain models. The side effects of FENPFF01 were further investigated through antinociceptive tolerance, respiratory function, addiction potential and gastrointestinal transit tests.</p><p><strong>Key results: </strong>FENPFF01 functioned as a mixed partial agonist at the μ-opioid and NPFF₂ receptors, and a full agonist at NPFF₁ receptor. Subcutaneous FENPFF01 produced potent antinociception in acute, inflammatory and post-operative pain, which was mediated by the μ receptor. The in vivo pharmacological and pharmacokinetic data demonstrated that FENPFF01 could penetrate the blood-brain barrier (BBB) and activate the μ receptor in the brain to elicit antinociception. Importantly, chronic administration of FENPFF01 did not induce antinociceptive tolerance or observable effects on spinal microglial activation, which may be partly attributable to the activation of the NPFF₂ receptor. FENPFF01 also did not affect arterial gas parameters, respiratory rate, locomotor activity, conditioned place preference response, physical dependence and gastrointestinal transit.</p><p><strong>Conclusions and implications: </strong>The newly developed peptide-drug conjugate FENPFF01 exhibited strong antinociception with reduced opioid-like side effects. It represents an interesting candidate for developing novel analgesics with multi-targeted agonist properties, aiming to address the widespread issues associated with opioid misuse.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin II-induced phosphorylation of CHK1 at serine-280 drives cardiac remodelling by direct phosphorylation of JAK1, thus activating JAK1-STAT signalling in murine cardiomyocytes.","authors":"Zheng Xu, Yihan Shen, Xiaoting Luo, Jingru Wang, Qian Zhou, Xue Han, Juan Ren, Lihong Wang, Guang Liang","doi":"10.1111/bph.70180","DOIUrl":"https://doi.org/10.1111/bph.70180","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cardiac remodelling is a common pathological process of heart disease. Checkpoint kinase 1 (CHK1), a key regulator of the DNA damage response and cell cycle, is well-studied in oncology, but its role in pathological cardiac remodelling remains unclear. Here, we investigated the activation of CHK1 and its effects in mouse models of cardiac remodelling induced by angiotensin II.</p><p><strong>Experimental approach: </strong>We used co-immunoprecipitation and mass spectrometry (Co-IP/MS) to identify the substrate kinase of CHK1. Cardiac remodelling in C57BL/6 mice and hypertrophy in primary neonatal rat cardiomyocytes (NRCMs) was induced with angiotensin II. These models were treated with the CHK1 selective inhibitor CCT245737 or the JAK1 inhibitor upadacitinib.</p><p><strong>Key results: </strong>In vitro and in vivo, angiotensin II selectively activated phosphorylation of CHK1 at serine-280 (S280), but not at S345, in cardiomyocytes, without altering levels of CHK1 protein. Inhibition of CHK1 with CCT245737 suppressed angiotensin II-induced hypertrophy in NRCMs. Such hypertrophy was enhanced by the phospho-mimetic CHK1 S280E mutant but was attenuated by the inactivating CHK1 S280A mutant. Co-IP/MS revealed that, in cardiomyocytes, JAK1 is the substrate protein of CHK1. Angiotensin II promoted CHK1 interaction with JAK1 to induce JAK1 phosphorylation and activation of JAK1-STAT3 signalling. In mice, both CCT245737 and upadacitinib reversed angiotensin II-induced cardiac remodelling and dysfunction.</p><p><strong>Conclusions and implications: </strong>Cardiomyocyte CHK1 S280 phosphorylation is a key step in angiotensin II-induced cardiac remodelling, through activation of the JAK1-STAT3 pathway. Pharmacological inhibition of CHK1 could be a potential therapeutic strategy for hypertensive heart failure.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Δ9-tetrahydrocannabinol exposure during adolescence is associated with persistent behavioural tolerance in adult nonhuman primates","authors":"Yasaman Razavi,&nbsp;Stephen J. Kohut,&nbsp;Jack Bergman,&nbsp;Brian D. Kangas","doi":"10.1111/bph.70179","DOIUrl":"10.1111/bph.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Legalisation of <i>Cannabis</i> use has led to considerable increases in the availability and potency of <i>Cannabis</i> products, as well as evolving patterns in methods of their consumption. Adolescent <i>Cannabis</i> use has increased, which can impair cognitive function during this critical developmental stage. The persistence of such effects into adulthood, however, is unclear. The present study examined whether chronic Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exposure during adolescence modifies subsequent Δ⁹-THC-induced cognitive deficits during adulthood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Approach</h3>\u0000 \u0000 <p>Female and male adolescent nonhuman primates were treated intramuscular daily for 6 months with either vehicle, a low dose of Δ⁹-THC (0.32 mg kg⁻¹ day⁻¹), or a high dose (3.2 mg kg⁻¹ day⁻¹). Approximately 1 year after discontinuing chronic exposure, these subjects, now adults, were trained on a touchscreen-based Psychomotor Vigilance Task (PVT) to examine attentional processes. Acute doses of Δ⁹-THC were administered prior to select test sessions via two routes, intramuscular or oral, to evaluate the roles of adolescent drug history and method of consumption on Δ⁹-THC-induced attentional deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key Results</h3>\u0000 \u0000 <p>Results confirm dose-related Δ⁹-THC impairment of PVT performance by both intramuscular and oral routes of administration, notwithstanding differences in potency and onset of action. Adolescent drug history modified tolerance to Δ⁹-THC impact on attentional processes, where subjects exposed to chronic Δ⁹-THC during adolescence required higher doses of Δ⁹-THC during adulthood to impair PVT performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Implications</h3>\u0000 \u0000 <p>These findings suggest a persistent impact of adolescent Δ⁹-THC use that, even following extended abstinence, may present itself during adulthood via increased tolerance to <i>Cannabis</i> products.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":"182 21","pages":"5149-5156"},"PeriodicalIF":7.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}