Olopade, EAdefegha, SAlao, JAdepoju, AFakayode, AOboh, G2025-02-272025-02-272025-02-17Basic and Clinical Pharmacology and Toxicology, ISSN: 1742-7835 (Print); 1742-7843 (Online), Wiley, 136(3), e70010-. doi: 10.1111/bcpt.700101742-78351742-7843http://hdl.handle.net/10292/18783Male sexual dysfunction, characterised by reduced libido, ejaculatory issues and erectile dysfunction, often results from oxidative stress and enzymatic imbalance, notably involving phosphodiesterase type 5 (PDE5) and nitric oxide synthase (NOS). This study explores the therapeutic potential of β-caryophyllene (β-CBP), a sesquiterpene with antioxidant and anti-inflammatory properties, in mitigating paroxetine-induced sexual dysfunction in rats. Male Wistar rats were divided into nine treatment groups: control, paroxetine (20 mg/kg/day), sildenafil (20 mg/kg/day), β-CBP (10 mg/kg/day), β-CBP (20 mg/kg/day), paroxetine with β-CBP (10 mg/kg), paroxetine with β-CBP (20 mg/kg), paroxetine with sildenafil and β-CBP with sildenafil. Sexual behavioural assays were evaluated, along with oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activity in penile tissue, assessed using spectrophotometric analysis. CB2 receptor expression was significantly increased in β-CBP-treated groups, suggesting enhanced cannabinoid receptor-mediated signalling, which may be linked to improved erectile function. The effects were dose-dependent, with the 20 mg/kg β-CBP group displaying the most significant improvements. Additionally, β-CBP restored antioxidant enzyme activities, including SOD, CAT and reduced glutathione (GSH) levels in penile tissue, effectively reducing oxidative stress. β-CBP shows promise as a therapeutic agent for male sexual dysfunction by enhancing antioxidative capacity and modulating enzymatic balance.© 2025 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Open access publishing facilitated by Auckland University of Technology, as part of the Wiley - Auckland University of Technology agreement via the Council of Australian University Librarians. https://creativecommons.org/licenses/by-nc/4.0/https://creativecommons.org/licenses/by-nc/4.0/CB2erectile dysfunctionoxidative stressparoxetineβ‐caryophyllene3214 Pharmacology and Pharmaceutical Sciences32 Biomedical and Clinical SciencesContraception/ReproductionUrologic Diseases5.1 Pharmaceuticals1115 Pharmacology and Pharmaceutical SciencesPharmacology & Pharmacy3214 Pharmacology and pharmaceutical sciencesMaleAnimalsRats, WistarPolycyclic SesquiterpenesAntioxidantsOxidative StressRatsCatalaseBiomarkersParoxetineDisease Models, AnimalSexual Behavior, AnimalSuperoxide DismutaseErectile DysfunctionReceptor, Cannabinoid, CB2Sildenafil CitrateSexual Dysfunction, PhysiologicalPenisMaleAnimalsRats, WistarPolycyclic SesquiterpenesAntioxidantsOxidative StressRatsCatalaseBiomarkersParoxetineDisease Models, AnimalSexual Behavior, AnimalSuperoxide DismutaseErectile DysfunctionReceptor, Cannabinoid, CB2Sildenafil CitrateSexual Dysfunction, PhysiologicalPenisJournal ArticleOpenAccess10.1111/bcpt.70010