Cannabinoid pharmacology and its therapeutic uses in Alzheimer's disease.

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From: Neural Regeneration Research(Vol. 16, Issue 5)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Article
Length: 1,980 words
Lexile Measure: 1300L

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Byline: Kadja. Monteiro, Marcone. dos Santos Alcântara, Thiago. de Aquino, Edeildo. da Silva-Júnior

Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is difficult to diagnose in its early stages. It is associated with aging and consists of a decline in cognitive functions, memory, and other mental activities. Some pathophysiological markers are associated with AD progression and worsening, such as the deposition and intracellular accumulation of senile plaques containing amyloid-ß (Aß) peptides, and tau protein hyperphosphorylation, leading to the formation of neurofibrillary tangles. Normally, this process leads to neuronal death and impaired inter-neuronal communication. Cannabis sativa is one of the oldest and well-known medicinal plants from the Cannabaceae family. More than 500 different compounds have been reported in their composition, in which cannabinoids stand out as compounds pharmacologically relevant for several pathologies (Premoli et al., 2019; Li et al., 2020). In this context, cannabidiol (CBD) is one of the most well-known phytocannabinoid used in the treatment of AD. In general, it presents low-toxicity, poor systemic absorption via oral administration of capsules or aqueous emulsions by humans and animals, and good bioavailability after feeding. Although several studies have highlighted the potential of THC ([DELTA]9-tetrahydrocannabinol, or [DELTA]9-THC), CBD targeting AD has been investigated recently. CBD and other cannabinoids are studied toward other psychiatric diseases, such as epilepsy, psychotic disorders, Parkinson's disease, anxiety disorders, and depression. Among its various pharmacological applications, it also demonstrates anticonvulsive, antipsychotic, anti-nausea, anti-inflammatory, and anti-rheumatoid arthritis properties. The endocannabinoid system is an endogenous system responsible for regulating physiological processes by endogenous cannabinoids, such as anandamide (AEA), 2-arachidonylglycerol (2-AG), and 2-arachidonyl glyceryl ether (2-AGE or noladin ether). The endocannabinoid system has two main receptors, CB1, which is present in the central nervous system and is responsible for memory, emotional processing, and appetite regulation; while CB2 is present in the peripheral nervous system and central nervous system, in cells from the immune system, which is responsible for immune responses modulation, such as inflammation. During AD, the endocannabinoid system undergoes some changes, where the progress of the disease may be related to the CB1 levels, in addition to the alteration of the CB2 expression, which starts to be expressed only in microglial cells. Thereafter, it is also observed the decreased AEA levels in cortical areas from the brain, which is related to the loss of cognitive ability. The potential neuroprotective ability of natural cannabinoids, such as CBD and THC, has increased the interest of research groups in studies targeting endocannabinoids. The neuroprotective functions of AEA and noladin ether in Aß-mediated neurotoxicity have been proven. The AM251, a CB1 receptor antagonist, prevented the protective effects of endocannabinoids. Notwithstanding this fact, an inhibitor of the mitogen-activated protein kinase pathway, PD98059, was also able to inhibit the protective effects of AEA and noladin ether, suggesting a probable role of mitogen-activated protein kinase in Aß-induced neurodegeneration. The endocannabinoid 2-AG exhibits anti-inflammatory and neuroprotective effects by interacting with the CB1 receptor, which has led to an interest in the exogenous application...

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Gale Document Number: GALE|A642710648