ArticleBiology of sex differences2026
Sex-dependent effects of ultra-low-dose-THC preventive treatment on neuroinflammation and cognitive decline in 5xFAD mice.
Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Cannabinoids in Alzheimer's disease: animal-human evidence and clinical pharmacology challenges.Frontiers in behavioral neuroscience · 2026Review
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Abstract
backgroundAlzheimer's disease (AD) remains the most prevalent cause of dementia, yet no existing treatment effectively prevents its onset. Current therapies primarily aim to slow disease progression or manage symptoms, leaving a critical gap in preventive strategies. Recent findings suggest that ultra-low-dose tetrahydrocannabinol (ULD-THC) may exert neuroprotective effects without the adverse consequences associated with chronic THC use. This study investigates whether preventive ULD-THC treatment can mitigate neuroinflammation and early cognitive decline in the 5xFAD mouse model of AD, with a specific focus on sex differences in treatment response.
methodsMale and female 5xFAD mice received monthly ULD-THC injections from 3 to 5 months of age, before significant pathology emerged. At 6 months, behavioral assessments were conducted, followed by molecular analyses of hippocampal and prefrontal cortex (PFC) tissue.
resultsResults indicated that ULD-THC attuned AD-related cognitive decline in both males and females, with sex-specific neuroinflammatory responses. Males exhibited reduced hippocampal inflammation, whereas females showed reduced inflammation in the PFC, suggesting distinct neuroprotective mechanisms across sexes.
conclusionsThese findings highlight ULD-THC's potential as a preventive strategy for AD, emphasizing the importance of sex-dependent therapeutic approaches. By attenuating neuroinflammatory processes before cognitive deficits fully manifest, ULD-THC offers a novel, biologically targeted approach to AD prevention. Future research should explore its long-term efficacy and translational potential in clinical settings.
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