The use of cannabinoids in the treatment of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive decline, memory loss, difficulties in daily activities, and an impact on quality of life. Its pathophysiology involves the accumulation of β-amyloid plaques and neurofibrillary tangles of TAU protein, associated with brain atrophy, chronic inflammation, and neuronal death. In addition to cognitive deficits, AD causes neuropsychiatric symptoms such as anxiety, agitation, apathy, and sleep disorders, which aggravate the patient's burden. Current treatments, such as cholinesterase inhibitors and glutamate antagonists, have only symptomatic effects and many adverse reactions. In this scenario, cannabinoids emerge as promising because they have neuroprotective and anti-inflammatory actions, in addition to improving behavioral symptoms, benefiting cognition and memory, and also reducing β-amyloid plaques. This Integrative Literature Review, based on Evidence-Based Practice, used the PICo strategy to formulate the question about the use of cannabinoids in elderly people with Alzheimer's disease. The search was conducted in the SciELO, LILACS, PubMed/MEDLINE, and Web of Science databases, using DeCS and MeSH descriptors, covering studies from 2015 to 2025. The selection followed the PRISMA protocol, and the data were systematized in a summary table, with an assessment of the level of evidence according to the Joanna Briggs Institute criteria. Cannabinoids, especially CBD, have been observed to show therapeutic potential in Alzheimer's disease, reducing agitation, anxiety, and sleep disturbances, with a good tolerability profile. CBD also exerts neuroprotective effects, modulating the TAU protein and the formation of beta-amyloid plaques, oxidative stress, and neuroinflammation via the endocannabinoid system. Other cannabinoids, such as dronabinol and nabilone, have also demonstrated the ability to mitigate nocturnal agitation and resistance during care. However, clinical research has focused on the use of CBD alone or combined formulations of THC and CBD to optimize efficacy and safety. Despite promising results, clinical evidence remains limited by the lack of large-scale randomized, placebo-controlled clinical trials, and further studies are needed.