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Study breakdown

Oral CBD slowed disease progression and improved cognitive deficits in ALS mice differently by sex

Animal StudyModerate evidence
The takeaway

Chronic oral CBD treatment delayed weight loss in female ALS mice and improved specific cognitive and social deficits in a sex-dependent manner, but did not improve motor function.

ALS researchers, neurologists studying cannabinoid therapeutics, and scientists investigating sex differences in treatment response.

What the researchers found

CBD (36 mg/kg/day oral) ameliorated weight loss in female SOD1G93A mice, tended to restore sociability in males, strengthened social recognition memory in females, and improved prepulse inhibition in younger females. CBD did not improve motor impairments in either sex.

Why it matters

ALS affects cognition and behavior in addition to motor function, but these aspects are often overlooked. This study shows CBD may address some non-motor ALS symptoms even when motor decline continues, and that effects differ meaningfully between sexes.

The numbers in context

36 mg/kg/day oral CBD. Treatment from 10 weeks. Weight loss ameliorated in females. Social recognition improved in females. PPI improved in younger females. No motor improvement in either sex.

How the study worked

Male and female SOD1G93A and wild-type mice fed control or CBD-enriched chow (36 mg/kg/day) from 10 weeks of age. Behavioral testing included rotarod, open field, prepulse inhibition, social behavior, and fear-associated memory from 11-19 weeks.

What this study cannot tell us

Only one dose tested. Motor benefits observed with CBDA in another study were not seen with CBD, possibly due to different model (SOD1 vs TDP-43), route, or dose. Sex-specific effects were not always consistent across measures.

How to read the evidence

Well-designed study with both sexes, multiple behavioral domains, and chronic oral dosing, though limited to one dose and one ALS model.

When this study was published

2025 publication.

The bigger picture

Combined with the CBDA study (RTHC-06508), this suggests different cannabinoid forms may target different ALS symptoms. CBDA showed motor benefits while CBD here improved cognitive/social domains, raising the possibility of complementary cannabinoid approaches.

Questions still open

  • Would combining CBD with CBDA address both motor and non-motor ALS symptoms?
  • Why does CBD improve non-motor but not motor symptoms in this ALS model?

Common questions

Why didn't CBD improve motor function in ALS mice?
The SOD1G93A model may respond differently than the TDP-43 model where CBDA showed motor benefits. Different cannabinoid forms, doses, and ALS subtypes may require different approaches. Motor neuron protection may need earlier intervention or different compounds.
What cognitive problems occur in ALS?
Up to 50% of ALS patients develop cognitive and behavioral changes, including problems with social cognition, executive function, and emotional processing. These non-motor symptoms significantly impact quality of life but receive less research attention than motor decline.

Read the original research

Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis.

Psychopharmacology, 242(9), 2077-2095

Citation

Ghimire, Sandip; Kreilaus, Fabian; Rosa Porto, Rossana; Anderson, Lyndsey L; Yerbury, Justin J; Arnold, Jonathon C; Karl, Tim. (2025). Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1G93 A) mouse model of amyotrophic lateral sclerosis.. Psychopharmacology, 242(9), 2077-2095. https://doi.org/10.1007/s00213-025-06785-z

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