Dylan T. Marsh, Ayato Sugiyama, Yuta Imai, Ryuji Kato, Scott D. Smid
September 11, 2023
Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells.
Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.
Cannabidiol inhibited lipid peroxidation with no significant effect on Aβ toxicity, while cannabinol, cannabidivarin and cannabigerol provided neuroprotection. Cannabichromene, cannabigerol and cannabinol inhibited Aβ1-42-induced neurotoxicity in PC12 cells, as did Δ9-tetrahydrocannabinol, cannabidiol and cannabidivarin. Cannabichromene, cannabinol and cannabidivarin inhibited Aβ aggregation, while Δ9-tetrahydrocannabinol reduced aggregate density. Aβ1-42 induced morphological changes in PC12 cells, including a reduction in neuritic projections and rounded cell morphology. Cannabichromene and cannabigerol inhibited this effect, while Δ9-tetrahydrocannabinol, cannabidiol and cannabidivarin did not alter Aβ1-42 effects on cell morphology.
These findings highlight the neuroprotective activity of cannabichromene, cannabigerol and cannabinol as novel phytocannabinoids associated with variable effects on Aβ-evoked neurite damage and inhibition of amyloid β aggregation.
Marsh, D. T., Sugiyama, A., Imai, Y., Kato, R., & Smid, S. D. (2023). The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid β‐evoked neurotoxicity and changes in cell morphology in PC12 cells. Basic & Clinical Pharmacology & Toxicology.