Revisiting health state preferences after 20 years: A new EQ-5D-3L value set for the Netherlands.

Cannabidiol (CBD), the second most significant phytocannabinoid in the plant Cannabis sativa, which lacks potential as a drug of abuse (Viudez-Martinez et al., 2019), has gained widespread attention due to its anti-inflammatory, antioxidant, and antidepressant properties (Garcia-Gutierrez et al., 2020). Additionally, CBD exhibits neuroprotective properties, preserving neuronal viability and function by preventing or limiting cellular damage. Our team has demonstrated that CBD produces rapid antidepressant-like effects in a murine model of chronic mild stress, restoring hippocampal expression of brain-derived neurotrophic factor (BDNF), serotonin 1A (5-HT), and peroxisome proliferator-activated receptor delta (PPARδ), and surpassing the effects of the conventional selective serotonin reuptake inhibitor sertraline. Similarly, CBD promotes hippocampal neurogenesis and enhances synaptic plasticity (Garcia-Gutierrez et al., 2023). Besides, CBD restores hippocampal neurodegeneration in a mouse model of fetal alcohol spectrum disorder (Gasparyan et al., 2023). Although cumulative evidence suggests the neuroprotective properties of CBD, emerging data reveal its ability to enhance regenerative processes by influencing progenitor proliferation, axonal sprouting, remyelination, synaptic reorganization, and glial phenotype modulation. We propose positioning CBD as a pro-regenerative modulator capable of enhancing repair in the central nervous system, beyond its protective role. This perspective explores potential mechanisms through which CBD promotes regeneration, including the modulation of neurotrophic factors and key signaling pathways, such as cannabinoid receptors, peroxisome proliferator-activated receptors (PPARs), and transient receptor potential vanilloid (TRPV) channels, as well as glial reprogramming. By shifting the paradigm from symptomatic neuroprotection to tissue repair and functional recovery, CBD could open new therapeutic avenues in regenerative neurology.