Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model |
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| Institution: | 1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China;2. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China;3. Hanma Investment Group Co., Ltd., Beijing, China;4. Yunnan Hempmon Pharmaceuticals Co. Ltd., Beijing, China;5. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China;6. Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Bialystok, Poland;1. Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo (FMRP-USP), Bandeirantes Avenue 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil;2. Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Brazil;3. Department of Psychiatry, Yale University School of Medicine, 34 Park Street 06520, New Haven, CT, United States;1. Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil;2. Institute of Neurosciences and Behavior (INeC), Universitz of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil;3. Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil;4. National Institute of Science and Technology for Translational Medicine (INCT-TM-CNPq), Ribeirão Preto, São Paulo, Brazil;1. Department of Pharmaceutics, University of Florida, Gainesville, United States;2. Department of Psychiatry, University of Florida, Gainesville, United States;1. Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy;2. CNR NANOTEC, Campus Ecotekne, Via Monteroni, 73100 Lecce, Italy;3. Department of Diagnostic Medicine, Clinical and Public Health, University of Modena and Reggio Emilia, Largo del pozzo 71, 41125 Modena, Italy;4. Department of Biomedical, Metabolic and Neural Sciences, Università di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy;5. Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy;6. Linnea SA, Via Cantonale, 6595 Riazzino, Switzerland;1. Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (Universidad de Cantabria, CSIC, SODERCAN), Departamento de Fisiología y Farmacología, Universidad de Cantabria, 39011 Santander, Spain;2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain;3. Departamento de Neuroquímica y Neurofarmacología, Instituto de Investigaciones Biomédicas de Barcelona, CSIC, IDIBAPS, 08036, Barcelona, Spain;1. CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China;2. School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China;3. Department of Druggabilty Evaluation, Topharman Shanghai Co., Ltd., Shanghai, 201203, China |
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| Abstract: | Cannabidiol (CBD) exhibits significant efficacy in mental and inflammatory diseases. Several studies have recently reported on the rapid antidepressant-like effects of CBD, suggesting that CBD is a potential anti-depressant or anti-stress drug. However, CBD is mainly administered orally or by inhalation with poor bioavailability, resulting in high costs. We aim to explore the efficacy of long-term periodic administration of CBD in chronic mild stress (CMS) via two routes and its pharmacokinetics. We treated ICR mice with CBD administered orally and intravenously and then determined the kinetic constants. A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%. The antidepressant-like effects of periodically administered CBD on the chronic mild stress mouse model are evaluated. Results demonstrated that such treatment at a high dose of 100 mg/kg CBD (p.o.) or a low dose of 10 mg/kg CBD (i.v.), elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. Our findings are expected to provide a reference for the development of intravenous antidepressant formulations of CBD. |
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| Keywords: | Cannabidiol Pharmacokinetics Depression CMS CBD |
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