ผลของ CBD และสารในกลุ่ม Terpene จากกัญชาสายพันธุ์ Cannabis sativa L.   (Hang Kra Rog Phu Phan ST1) ต่อการเสริมฤทธิ์หรือต้านฤทธิ์ในการลดอัตราการตายของเซลล์ SH-SY5Y ที่เกิดจาก Amyloid-β1-

Pathomporn Eamjai; Nuntachai Hanpramukkun; Chatchawan Singhapol

Authors

Pathomporn Eamjai Department of Biotechnology, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok, 10800, Thailand
Nuntachai Hanpramukkun College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand
Chatchawan Singhapol Department of Biotechnology, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok, 10800, Thailand

Keywords:

Alzheimer, CBD, Terpenes, Prevention and Treatment, Cellular Apoptotic from amyloid-β1-42.

Abstract

Dementia, particularly Alzheimer’s Disease (AD), is characterized by the extracellular accumulation of Amyloid-β (Aβ) and intracellular Tau hyperphosphorylation, both of which trigger neuroinflammation and neuronal apoptosis. This study investigated the efficacy of Cannabidiol (CBD) combined with three terpenes including α-Pinene, Linalool, and β-Caryophyllene as potential adjuvants to mitigate Aβ_1-42-induced neurotoxicity. Using the MTT assay on SH-SY5Y neuroblastoma cells, the optimal non-toxic concentrations were determined to be 150 µM for CBD, α-Pinene, and Linalool, and 100 µM for β-Caryophyllene. Synergistic testing revealed that the combination of CBD with α-Pinene and CBD with Linalool significantly reduced cell mortality (p < 0.01) when administered post-Aβ_1-42accumulation, demonstrating a potential curative effect. However, pre-treatment with these combinations failed to provide a preventive effect against subsequent Aβ_1-42insult. Notably, the combination of CBD with β-Caryophyllene, or the administration of more than two compounds simultaneously, resulted in increased cytotoxicity and significantly higher rates of cell death. These findings suggest that while certain cannabinoid-terpene combinations offer therapeutic potential, their application is limited by specific chemical interactions and timing. Further research into precise formulations and intervention windows is essential to develop safe and effective cannabis-based treatments for Alzheimer's Disease

References

Ali, M., Timsina, J., Western, D., Liu, M., Beric, A., Budde, J., et al. (2025). Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum. Neuron, 113(9), 1363-1379.e1369. https://doi.org/10.1016/j.neuron.2025.02.014

Beltrami, S., Rizzo, S., Schiuma, G., Cianci, G., Narducci, M., Baroni, M., et al. (2025). West Nile virus non-structural protein 1 promotes amyloid Beta deposition and neurodegeneration. International Journal of Biological Macromolecules, 305, 141032. doi:https://doi.org/10.1016/j.ijbiomac.2025.141032

Chen, L., Sun, Y., Li, J., Liu, S., Ding, H., Wang, G., & Li, X. (2023). Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration. Cells, 12(23), 2672. https://doi.org/10.3390/cells12232672

Doering, S., McCullough, A., Gordon, B. A., Chen, C. D., McKay, N., Hobbs, D., .et al. (2024). Deconstructing pathological tau by biological process in early stages of Alzheimer disease: a method for quantifying tau spatial spread in neuroimaging. eBioMedicine, 103, 105080. doi:https://doi.org/10.1016/j.ebiom.2024.105080

El-Hammadi, M. M., Small-Howard, A. L., Fernández-Arévalo, M., Turner, H., & Martín-Banderas, L. (2025). Effects of combined CBGA and cannabis-derived terpene nanoformulations on TRPV1 activation: Implications for enhanced pain management. International Journal of Pharmaceutics, 679, 125766. doi:https://doi.org/10.1016/j.ijpharm.2025.125766

Esposito, G., Scuderi, C., Valenza, M., Togna, G. I., Latina, V., De Filippis, D., Cipriano, M., Carratù, M. R., Iuvone, T., & Steardo, L. (2011). Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PloS one, 6(12), e28668. https://doi.org/10.1371/journal.pone.0028668

Greeley, D., Nash, M., Herskowitz, B., Kim, F., Rock, J., Prins, N., et al. (2025). A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhibitor, in patients with mild-to-moderate Alzheimer’s disease. The Journal of Prevention of Alzheimer's Disease, 100337. doi:https://doi.org/10.1016/j.tjpad.2025.100337

Harvey, B. S., Ohlsson, K. S., Mååg, J. L. V., Musgrave, I. F., & Smid, S. D. (2012). Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro. NeuroToxicology, 33(1), 138-146. doi:https://doi.org/10.1016/j.neuro.2011.12.015

Janefjord, E., Mååg, J. L., Harvey, B. S., & Smid, S. D. (2014). Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cellular and molecular neurobiology, 34(1), 31–42. https://doi.org/10.1007/s10571-013-9984-x

Kang, S., Li, J., Yao, Z., & Liu, J. (2021). Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways. Frontiers in cellular neuroscience, 15, 654340. https://doi.org/10.3389/fncel.2021.654340

Kim, H.-K., Park, S., Kim, S.-W., Jin, Y., Lee, H., Hong, J. Y., et al. (2025). Associations between traumatic brain injury and the prevalence of Alzheimer’s disease dementia and behavioral and psychological symptoms of dementia: A retrospective cohort study. The Journal of Prevention of Alzheimer's Disease, 100360. doi:https://doi.org/10.1016/j.tjpad.2025.100360

Laws, J. S., & Smid, S. D. (2024). Characterizing cannabis-prevalent terpenes for neuroprotection reveal a role for α and β-pinenes in mitigating amyloid β-evoked neurotoxicity and aggregation in vitro. NeuroToxicology, 100, 16-24. doi:https://doi.org/10.1016/j.neuro.2023.12.004

Levy, C. M., Riederer, A. M., Simpson, C. D., Gassett, A. J., Gilbert, A. J., Paulsen, M. H., et al. (2025). Forest terpenes and stress: Examining the associations of filtered vs. non-filtered air in a real-life natural environment. Environmental Research, 276, 121482. doi:https://doi.org/10.1016/j.envres.2025.121482

Li, D., Ilnytskyy, Y., Ghasemi Gojani, E., Kovalchuk, O., & Kovalchuk, I. (2022). Analysis of anti-cancer and anti-inflammatory properties of 25 high-THC cannabis extracts. Molecules, 27(18), 6057 doi:https://doi.org/10.3390/molecules27186057

Sabogal-Guáqueta, A. M., Osorio, E., & Cardona-Gómez, G. P. (2016). Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice. Neuropharmacology, 102, 111–120. https://doi.org/10.1016/j.neuropharm.2015.11.002

Santos, N. A., Martins, N. M., Sisti, F. M., Fernandes, L. S., Ferreira, R. S., Queiroz, R. H., & Santos, A. C. (2015). The neuroprotection of cannabidiol against MPP⁺-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicology in vitro : an international journal published in association with BIBRA, 30(1 Pt B), 231–240. https://doi.org/10.1016/j.tiv.2015.11.004

Tendwa, M. B., Appidi, T., Chitsunge, B., Moreau, M., Okole, B., Kalombo, L., et al. (2025). From farm to bedside: Potential of medical cannabis in global health. Complementary Therapies in Medicine, 93, 103205. doi:https://doi.org/10.1016/j.ctim.2025.103205

Yang, F., Duan, S., Liu, J., An, Z., Liu, W., Wang, X., et al. (2025). Antitumor effects of cannabidiol (CBD) on osteosarcoma by targeting TNF-α/NF-κB/CCL5 signaling axis. Phytomedicine, 145, 157066. doi:https://doi.org/10.1016/j.phymed.2025.157066

Zhang, Y., Li, H., Jin, S., Lu, Y., Peng, Y., Zhao, L., & Wang, X. (2022). Cannabidiol protects against Alzheimer's disease in C. elegans via ROS scavenging activity of its phenolic hydroxyl groups. European journal of pharmacology, 919, 174829. https://doi.org/10.1016/j.ejphar.2022.174829