Phytocannabinoids: a new frontier in Alzheimer’s disease management

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and behavioral disturbances. The pathogenic characteristics encompass the existence of amyloid plaques outside the cells, neurofibrillary tangles inside the cells, neuroinflammation, oxidative stress, and the loss of synapses. The altered brain endocannabinoid system (ECS) has been linked to the progression of AD. The ECS consists of endocannabinoids, metabolic enzymes, and their receptors, CB1R and CB2R. Individuals have utilized therapeutic cannabis-derived remedies for medicinal purposes. The cannabis plant is composed of a diverse range of phytocannabinoids, terpenes, and phenolic compounds. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are plant-derived compounds that have been well researched. Both phytocannabinoids contribute to physiological and pharmacological effects. Multiple preclinical studies conducted on animal models of AD have shown that THC specifically targets and modifies the pathological markers of AD while simultaneously enhancing cognitive function. Studies have shown that administering low amounts of THC can reduce the phosphorylation of tau, the accumulation of beta-amyloid proteins, and the levels of GSK3 beta. Moreover, it has the potential to enhance mitochondrial function. Furthermore, a study has shown that maintaining a balance between CB1R and CB2R is essential for stability in neuroinflammation, neurogenesis, and cognitive performance. At present, numerous FDA-controlled clinical trials are being conducted to assess the beneficial impacts of THC and CBD in the treatment of cognitive and neuropsychiatric symptoms associated with AD. This review article focuses on the therapeutic advantages of phytocannabinoids and their role in AD, the most common neurodegenerative disease.