“Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1^G93A).

Methods: Male and female SOD1^G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

Results: CBD treatment ameliorated the bodyweight loss in female SOD1^G93A mice, tended to reinstate sociability in SOD1^G93A males, strengthened social recognition memory in SOD1^G93A females, and improved the PPI response in younger SOD1^G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1^G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

Conclusion: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1^G93A mice in a sex specific manner without altering the motor phenotype.”

https://pubmed.ncbi.nlm.nih.gov/40229540/

“In conclusion, the study discovered beneficial effects of oral CBD on the bodyweight deficit in both male and female SOD1^{G93 A} mice as well as improving social recognition memory and the PPI response in female SOD1^{G93 A} mice. CBD also reduced the ASR and increased the freezing response to a conditioned cue in both SOD1^{G93 A} transgenic and WT male mice. However, CBD treatment did not reverse motor impairments or sensorimotor gating deficits. Thus, chronic oral CBD treatment at the dose administered here may be therapeutically useful for only particular ALS symptoms including bodyweight decline, which is an indicator of disease progression and declining survival rate (Dharmadasa et al. 2017). Further investigations should consider additional CBD dosing and beginning treatment at an earlier age prior to the onset of motor deficits. This could be followed by combination treatments of CBD and e.g. cannabinoid receptor antagonists to explore potential mechanisms behind observed CBD effects.”

https://link.springer.com/article/10.1007/s00213-025-06785-z