Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review

Abstract

Neurodegeneration leading to Parkinson’s disease (PD) and Alzheimer’s disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with l-DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ9-THC) and cannabidiol (CBD) cannabinoids of plant Cannabis sativa have shown neuroprotection upon PD and AD animal models yet triggered toxic effects on patients when administered directly. Therefore, understanding the precise molecular cascade following cannabinoid treatment is suggested, focusing especially on gene expression to identify drug targets for preventing and repairing neurodegeneration.

Cannabidiol in Neurological and Neoplastic Diseases: Latest Developments on the Molecular Mechanism of Action

“…The accumulation of extracellular aggregates of amyloid-β (Aβ) peptides in senile plaques, found in various parts of the brain, is one of the key factors of pathogenesis and progression of Alzheimer’s disease [ 32 , 33 ] and other diseases, such as Down’s syndrome, dementia with Lewy bodies, corticobasal degeneration, chronic traumatic encephalopathy [ 34 ]. It should be emphasized here that an increasing number of studies are focused on the molecular interaction of CBD with the amyloid pathway in vitro and in vivo [ 12 , 13 , 14 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

New paradigms for the treatment of lysosomal storage diseases: targeting the endocannabinoid system as a therapeutic strategy

“…We now know that the neural and behavioral effects of exogenously administered cannabinoids (e.g., tetrahydrocannabinol [THC], cannabidiol [CBD]) can be traced, at least in part, to the modulation of the ECS [ 22 ], although it was first described as an endogenous system controlling nervous system function. To elicit these broad effects, numerous downstream signaling events result from activation of the CB1/CB2 receptors by endogenous endocannabinoids.…”

Feline cognitive dysfunction as a model for Alzheimer’s disease in the research of CBD as a potential treatment—a narrative review

“…We did not find articles regarding clinical trials in treatment of AD or dementia with CBD. Additionally, a few recent comprehensive reviews that addressed the treatment of AD and dementia with cannabinoids did not review clinical trials with treatment of dementia or AD with CBD (Beedham et al 2020;Inglet et al 2020;Cooray et al 2020). A published case communication demonstrated treatment of an 81-year-old man that suffered from dementia after several cardiovascular events and presented with drowsiness, difficulty keeping his eyes open, inability to maintain eye contact for more than a few seconds, inability to speak, difficulties to communicate, and severe spasticity.…”