Cannabidivarin mitigates motor and cognitive impairments in a female mouse model of Rett syndrome

1. Life Sci. 2025 Oct 1;378:123846. doi: 10.1016/j.lfs.2025.123846. Epub 2025 Jul
7.

Cannabidivarin mitigates motor and cognitive impairments in a female mouse model
of Rett syndrome.

Lourenço DM(1), Zavalko S(1), Duarte AL(1), Sá-Santos S(2), Mateus JM(1),
Rodrigues RS(1), Miranda-Lourenço C(1), Mouro FM(1), Viais R(1), Sebastião
AM(1), Solá S(2), Diógenes MJ(1), Xapelli S(3).

Author information:
(1)Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; GIMM –
Gulbenkian Institute of Molecular Medicine, Lisboa, Portugal.
(2)Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia,
Universidade de Lisboa, 1649-003 Lisboa, Portugal.
(3)Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; GIMM –
Gulbenkian Institute of Molecular Medicine, Lisboa, Portugal. Electronic
address: .

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.

Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.lfs.2025.123846
PMID: 40633901 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors
declare no competing interests.

Auteurs Bordeaux Neurocampus