CANNABIS NA GERIATRIA E GERONTOLOGIA: ALZHEIMER

Abstract

Population aging is a global trend, with projections indicating that the number of people aged 65 and over is expected to double in the next three decades. With aging, the risk of chronic conditions such as dementia increases, which could account for 139 million cases by 2050. Alzheimer's disease ("AD"), recognized as a global public health problem, is the most prevalent cause of dementia and may account for 60-70% of cases. AD is characterized by memory deficits and deterioration of multiple cognitive functions, involving beta-amyloid protein deposits, tau protein neurofibrillary tangles, inflammation, and neuronal loss. Conventional treatments do not halt or reverse the neurodegenerative process. In this context, activation of the endocannabinoid system ("ECS"), which regulates physiological processes such as mood, appetite, and sleep, and whose activity is neuroprotective, emerges as a potential therapeutic approach for AD symptoms. Experimental and postmortem studies in human brains with AD have identified alterations in the ECS, with elevated levels of endocannabinoids (anandamide and 2-arachidonylglycerol) and their metabolizing enzymes in degenerated brain regions. Activation of CB1 and CB2 receptors (the main ECS receptors) by natural or synthetic agonists has demonstrated beneficial effects in experimental models of Alzheimer's disease, including reduced neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. Although still in its infancy, the use of cannabinoids in the treatment of Alzheimer's disease is a growing reality in Brazil and worldwide. Scientific data point to the ability of cannabinoids to reduce neuroinflammation, neurotoxicity, excitotoxicity, apoptosis, and oxidative stress, in addition to stimulating neurogenesis and cerebral blood flow. Symptoms such as insomnia, paranoia, anxiety, dysphoria, pain, appetite loss, and weight loss may respond to cannabis therapy. However, there is a need to expand access to the plant and the technical-scientific debate to improve knowledge about the cellular mechanisms of cannabinoids, as well as to conduct more long-term randomized controlled studies exploring different types of cannabis-based medicines, the neuroprotective potential of cannabinoid compounds, their underlying mechanisms, and their combinations.

Keywords: Alzheimer's; Cannabinoids; Endocannabinoid System; Neuroprotection.