Cannabidiol in Alzheimer's disease: evidence-weighted molecular mechanisms and translational challenges.

Sura S.; Jagadeesan S.; Masrudin S.; Moklas M.; Nor N. · Molecular biology reports · 2026

**Background & Methods** This is a comprehensive review article examining the molecular mechanisms by which cannabidiol (CBD), a non-psychotropic phytocannabinoid, may exert neuroprotective effects in Alzheimer's disease (AD). The authors synthesized preclinical evidence across multiple pathological domains relevant to AD pathogenesis, including amyloid-β accumulation, tau dysregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and synaptic loss. **Key Findings** • CBD demonstrates the most consistent preclinical evidence for attenuating neuroinflammatory and oxidative stress responses while improving selected behavioral outcomes in AD models, acting through multiple signaling pathways including cannabinoid receptors, PPAR-γ, TRPV1 channels, 5-HT1A signaling, and adenosine transporters. • Evidence for CBD's effects on amyloid-β is supportive but heterogeneous across studies; direct evidence for tau modulation has expanded in transgenic and chemically induced models, though findings remain model-dependent, while effects on mitochondrial rescue and adult hippocampal neurogenesis are less firmly established. • Current preclinical evidence does not establish CBD as a disease-modifying treatment for AD, but supports continued investigation as a multi-target neuroprotective candidate, particularly given modest clinical benefits of existing symptomatic and anti-amyloid therapies. **Dosage & Administration** Not reported. The review notes that methodological variability in CBD source, formulation, dose, and route of administration across studies significantly limits direct comparison between investigations. **Safety & Adverse Effects** Not reported. The review does not provide specific safety or adverse effect data from the analyzed studies. **Evidence Quality** This review identifies substantial methodological limitations across the preclinical literature, including significant variability in CBD source, formulation, dose, route of administration, treatment timing, sex and age of study subjects, and outcome measures selected. These factors substantially limit cross-study comparisons and generalizability. The authors emphasize that future studies require standardized, mechanism-focused, and translationally relevant designs to advance CBD from preclinical investigation toward potential clinical development. No human clinical trials are discussed, indicating that evidence remains entirely preclinical.

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