A1 Refereed original research article in a scientific journal
Investigative assessment of the neuro-modulatory potentials of cannabichromene in TrkB/BDNF-mediated neurosignaling pathway
Authors: Dosumu, Oluwatosin Adebisi; Taiwo, Odunayo Anthonia; Akomolafe, Victoria Omoyemi; Oni, Eniola Oluwayemisi; Ojo, Oluwafemi Adeleke; Dedeke, Gabriel Adewunmi; Ademuyiwa, Oladipo
Publisher: Springer Science and Business Media LLC
Publication year: 2025
Journal: Comparative Clinical Pathology
Journal name in source: Comparative Clinical Pathology
ISSN: 1618-5641
eISSN: 1618-565X
DOI: https://doi.org/10.1007/s00580-025-03659-w
Web address : https://doi.org/10.1007/s00580-025-03659-w
Cannabichromene (CBC) is the third most abundant non-psychoactive cannabinoid found in Cannabis sativa. It is reported to be responsible for some effects in users, ranging from psychological, neurodevelopmental, teratogenic to reproductive toxicity. Consequently, experimental evaluation of the mechanism of action and interaction seemed paramount. Therefore, this work determined the mechanism through which cannabichromene modulates neurosignaling using computational analysis and various biochemical investigative approaches. The effects of 3 weeks oral administration of 10 mg/kg body weight dose of CBC on some neurodevelopment biomarkers in the hippocampus and striatum of young male and female Wistar rats were investigated. Induced fit docking scores revealed that cannabichromene had the highest binding scores with tropomyosin receptor kinase B (TrkB) (− 797.23 kJ/mol)when compared with other cannabinoids. It also formed hydrogen bonds with amino acids GLU634, MET636 at the active site of the protein, thereby contributing to the stability of the protein–ligand complex. Neurosignaling enzymes (acetylcholinesterase (AChE) and monoamine oxidase MAO-A) activities were significantly (p < 0.05) increased in the CBC-exposed groups as well as malondialdehyde (MDA) concentration. Relative expressions of brain-derived neurotropic factor (BDNF) and dopamine receptor 1 (DR1) genes were significantly (p < 0.05) downregulated in the CBC groups relative to control, all indicative of a compromised neurosignaling mechanism. Furthermore, behavioral cognitive biomarkers, discrimination ratio (DR), and difference scores (DS) were significantly altered in the test animals, suggestive of impairment in short-term memory. Histological evaluations revealed aberrant histoarchitecture of brain tissues in CBC-exposed rats, characterized by congestion of the cortical capillaries, degeneration of neuronal cells, and focal gliosis. It may be deduced from this study that cannabichromene impaired hippocampal and striatal neurotransmission in adolescents by altering neurotransmitter dynamics, neuronal morphology, and gene expression, with potential implications for cognitive dysfunction and neurodegeneration.
Funding information in the publication:
This research received no external funding.
