Cannabidiol (CBD) reduces
seizures in childhood
epilepsy syndromes including
Dravet syndrome (DS). A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway. The mechanism responsible for CBD effects is not known, although it could involve targets sensitive to CBD in other
neurological disorders. We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the
endocannabinoid system is dysregulated. To this end, lymphocytes from patients and controls were used for analysis of gene expression of transmitter receptors and transporters,
ion channels, and
enzymes associated with CBD effects, as well as
endocannabinoid genes. Plasma
endocannabinoid levels were also analyzed. There were no differences between DS patients and controls in most of the CBD targets analyzed, except an increase in the
voltage-dependent calcium channel α-1h subunit. We also found that
cannabinoid type-2 (CB 2) receptor gene expression was elevated in DS patients, with no changes in other
endocannabinoid-related receptors and
enzymes, as well as in plasma levels of
endocannabinoids. Such elevation was paralleled by an increase in CD70, a marker of lymphocyte activation, and certain trends in
inflammation-related
proteins (e.g.,
peroxisome proliferator-activated receptor-γ
receptors, cytokines). In conclusion, together with changes in the
voltage-dependent calcium channel α-1h subunit, we found an upregulation of CB 2 receptors, associated with an activation of lymphocytes and changes in
inflammation-related genes, in DS patients. Such changes were also reported in inflammatory disorders and may indirectly support the occurrence of a potential dysregulation of the
endocannabinoid system in the brain.