Cannabidiol (CBD) treatment reduced the progression of the pathological phenotype in a mouse model of Dravet syndrome (DS), according to a new study published in Neuropharmacology. Treatment with β-caryophyllene (BCP) also produced the same beneficial effects, but combining the 2 cannabinoids led to superior effects.
“Our results support the interest to continue investigating the combination of BCP and CBD to improve the therapeutic management of DS in relation with their disease-modifying properties,” the authors concluded.
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They used 2 experimental approaches to compare the efficacy of CBD and BCP in DS as well as their possible additive effect.
In the first approach, they compared the 2 compounds and their combination in a mouse model of DS treated between days 10 and 24 after birth.
They found that both CBD and BCP administered on their own partially reduced the impairments in limb clasping, delays in the back leg grasp reflex, hyperactivity, cognitive deterioration, and social interaction deficits that are seen in these mice.
Both treatments, but especially BCP, also reduced the astroglial and microglial reactivities seen in the prefrontal cortex and hippocampal dentate gyrus in these animals.
When the 2 compounds were combined, superior effects were seen in a few specific parameters.
In the second experimental approach, the researchers evaluated the additive effects of the 2 compounds in cultured mouse microglial cells stimulated with lipopolysaccharide (LPS) to induce neuroinflammation.
Treatment with either compound led to a reduction in the elevation of inflammatory markers such as Toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), catalase, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Once again, a superior effect was seen when both compounds were combined.
“In summary, the in vivo and in vitro experiments carried out in this study support that the combined treatment of BCP and CBD might be a promising therapeutic strategy for the treatment of DS,” the researchers concluded, “although this will require additional studies.”
Reference
Alonso C, Satta V, Hernández-Fisac I, Fernández-Ruiz J, Sagredo O. Disease-modifying effects of cannabidiol, β-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome. Neuropharmacology. Published online June 7, 2023. doi:10.1016/j.neuropharm.2023.109602
