“Rett Syndrome (RTT, #312750 – OMIM) is a rare, progressive neurodevelopmental X-linked disorder, caused mostly by mutations in the gene for the methyl CpG binding protein 2 (MECP2). MECP2 is a transcriptional and epigenetic regulator that has been proposed to modulate neuronal development and adult neurogenesis, processes disrupted in both RTT patients and mouse models.
Cannabidivarin (CBDV), a non-psychotropic cannabinoid, has recently been shown to promote adult neurogenesis through a mechanism mediated by transient receptor potential cation channel subfamily V member 1 (TRPV1).
This study aimed to investigate the effects of chronic CBDV administration in a female RTT mouse model.
Pre-symptomatic Mecp2tm1.1Bird/J female mice underwent a chronic CBDV treatment (3 mg/kg/day), followed by behavioral tests to assess potential therapeutic effects.
While CBDV did not prevent deficits in locomotor activity, it mitigated motor coordination impairments in RTT mice. Furthermore, the novel object recognition test suggested that CBDV treatment contributed to the preservation of cognitive function in these animals. Moreover, CBDV administration induced genotype-dependent differences in neural stem cell proliferation, indicating a potential vulnerability in adult hippocampal neurogenesis in Mecp2-deficient contexts.
Taken together, these findings provide new insights into the role of CBDV in RTT and support for future research, highlighting its potential as a repurposed therapeutic agent.”
https://pubmed.ncbi.nlm.nih.gov/40633901/
“The data presented in this manuscript demonstrates the therapeutic potential of CBDV in improving behavioral and phenotypic abnormalities in a female mouse model of RTT. Additionally, CBDV differentially affects adult hippocampal neurogenesis in this model.”
https://www.sciencedirect.com/science/article/pii/S0024320525004813?via%3Dihub
“Rett syndrome (RTT) is a rare neurologic disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available.
“Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused mainly by mutations in the MECP2 gene, being one of the leading causes of mental disability in females.
“Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. RTT is caused by mutations in the MECP2 gene in about 95% of cases and to date no cure is available.
The endocannabinoid system modulates several physiological processes and behavioural responses that are impaired in RTT and its deregulation has been associated with neuropsychiatric disorders which have symptoms in common with RTT.
The present study evaluated the potential therapeutic efficacy for RTT of cannabidivarin (CBDV), a non-psychotropic phytocannabinoid from Cannabis sativa that presents antagonistic properties on the G protein-coupled receptor 55 (GPR55), the most recently identified cannabinoid receptor.
Present results demonstrate that systemic treatment with CBDV (2, 20, 100 mg/Kg ip for 14 days) rescues behavioural and brain alterations in MeCP2-308 male mice, a validated RTT model. The CBDV treatment restored the compromised general health status, the sociability and the brain weight in RTT mice. A partial restoration of motor coordination was also observed. Moreover, increased levels of GPR55 were found in RTT mouse hippocampus, suggesting this G protein-coupled receptor as new potential target for the treatment of this disorder.
Present findings highlight for the first time for RTT the translational relevance of CBDV, an innovative therapeutic agent that is under active investigation in the clinical setting.”
