Modulation of the Endocannabinoid System by Cannabis sativa Bioactives in Alzheimer’s Disease: Therapeutic and Nutritional Implications

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, oxidative stress, amyloid-β accumulation, and tau pathology. Current therapies provide limited symptomatic relief, highlighting the need for novel therapeutic and nutritional approaches. Objective: This review aimed to evaluate the therapeutic and nutritional implications of Cannabis sativa and its bioactive compounds in AD management, with emphasis on molecular mechanisms, clinical evidence, extraction technologies, and emerging therapeutic opportunities. Methods: A comprehensive review of the scientific literature was conducted, focusing on cannabinoids, non-cannabinoid phytochemicals, hemp-derived nutritional compounds, preclinical findings, clinical studies, and recent advances related to AD. Results: Evidence indicates that cannabinoids, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), may modulate neuroinflammation, oxidative stress, amyloid-β aggregation, tau hyperphosphorylation, and neuronal survival pathways. Emerging compounds, including acidic cannabinoids, minor cannabinoids, polyphenols, flavonoids, hemp-derived bioactive peptides, and root alkaloids, have demonstrated additional neuroprotective potential. Clinical studies primarily support cannabinoid-based interventions for improving behavioral and neuropsychiatric symptoms rather than modifying disease progression. Hemp seeds and hemp-derived products also provide nutritional bioactives with potential complementary benefits. Conclusion: Cannabis sativa represents a promising source of therapeutic and nutritional bioactive compounds for AD management. However, larger standardized clinical trials are required to confirm efficacy, safety, and disease-modifying potential before widespread clinical application can be recommended.