“Studies have reported changes in the endocannabinoid system in the brain of patients with Alzheimer’s disease (AD), playing a role in the pathophysiology of AD. Cannabinoids have been shown to have neuroprotective properties, reduce neuroinflammation, and enhance neurogenesis. Evidence suggests that the utilization of marijuana products containing both tetrahydrocannabinol (THC) and cannabidiol (CBD) or CBD alone have been effective and safe for use in older people with agitation associated with dementia.
A review in 2017 summarized positive findings for therapeutic benefits of cannabinoids in agitation of AD and dementia, but there was no definitive conclusion because of varying cannabinoid products. Cannabinoids were shown to be well tolerated, with few short-term side effects. This differs from first-line medications utilized for dementia behaviors, which can have unwanted side effects. Further research regarding the safety, efficacy, and variability of these products in older people is needed.”
“The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue.
“Alzheimer’s Dementia (AD) is a devastating neurodegenerative disease that affects approximately 17% of people aged 75-84. Neuropsychiatric symptoms (NPS) such as delusions, agitation, anxiety, and hallucinations are present in up to 95% of patients in all stages of dementia. To date, any approved and effective pharmacological interventions for the treatment of NPS are still not available.
“Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging.
“Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects.
“Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of “neuroinflammaging” has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging.
“While medical and recreational cannabis use is becoming more frequent among older adults, the neurocognitive consequences of cannabis use in this age group are unclear. The aim of this literature review was to synthesize and evaluate the current knowledge on the association of cannabis use during older-adulthood with cognitive function and brain aging.
“Microglia, the resident immune cells of the central nervous system, mediate brain homeostasis by controlling neuronal proliferation/differentiation and synaptic activity. In response to external signals from neuropathological conditions, homeostatic (M0) microglia can adopt one of two activation states: the classical (M1) activation state, which secretes mediators of the proinflammatory response, and the alternative (M2) activation state, which presumably mediates the resolution of neuroinflammation and tissue repair/remodeling.
“Alzheimer’s disease (AD) is characterized by progressive cognitive decline and pathologically by the accumulation of amyloid-β (Aβ) and tau hyperphosphorylation causing neurodegeneration and neuroinflammation. Current AD treatments do not stop or reverse the disease progression, highlighting the need for more effective therapeutics.
“Herein, 11 general types of natural cannabinoids from Cannabis sativa as well as 50 (-)-CBD analogues with therapeutic potential were described. The underlying molecular mechanisms of CBD as a therapeutic candidate for epilepsy and neurodegenerative diseases were comprehensively clarified. CBD indirectly acts as an endogenous cannabinoid receptor agonist to exert its neuroprotective effects. CBD also promotes neuroprotection through different signal transduction pathways mediated indirectly by cannabinoid receptors. Furthermore, CBD prevents the glycogen synthase kinase 3β (GSK-3β) hyperphosphorylation caused by Aβ and may be developed as a new therapeutic candidate for Alzheimer’s disease.”