This paper is a review of what was known at the time of publication about the role of the endocannabinoid system in brain health, regulation, and growth. How the endocannabinoid system acts as a sometimes neuroprotective system, and how dysfunction can lead to worsened outcomes, is explored.
The endocannabinoid system is involved in neuronal growth, differentiation, longevity, migration, protection, inflammation, and the immune response. The use of cannabinoids in the palliative care of multiple sclerosis and other neurodegenerative disease patients strongly indicates the potential for further therapeutic actions. However, at this time, the pathways and mechanisms that are exploited by current therapies are not fully understood.
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The implications of endocannabinoid interaction for therapy in neurodegenerative diseases is discussed in some detail, and the authors press for more research into the precise molecular mechanisms involved so more can be understood.
There are two main cannabinoid receptors, CB1 and CB2. They are “widely expressed in the nervous system”, from the brain to the peripheral sensory nerves, in non-nervous tissue like eyes, testes and skin. Both receptors are known to be involved in “motor function, cognitive processes, emotion, sensorial perception, endocrine functions and food intake”. The distribution of both receptors differs to some extent, especially in the brain.
This paper focuses particularly on neural progenitor cells (NPs). These are cells that will differentiate into different neuronal cell types and are crucial to the growth, development, regulation, and maintenance of nervous structures like the brain. The ECS has been shown to play a vital role in early brain development and later regulation. It is proposed that NPs can be the targets of ECS manipulation to exert control over their differentiation and lineage.
Of particular interest is the potential use of the ECS to treat neurodegenerative disorders such as stroke, Alzheimer’s, and Huntington’s disease. Neuroinflammation is a factor in these conditions and the anti-inflammatory effects of exogenous cannabinoids is well documented.
Other pathways by which the ECS can potentially be of benefit include neurogenesis, the production of new neurons and neuronal pathways. In Huntington’s, “striatal CB1 receptors are lost prior to the appearance of neurological deficits”, and so present an opportunity for a novel treatment pathway.
Other neurodegenerative diseases are discussed, including multiple sclerosis (MS). The loss of myelination on neuronal axons is the major cause of brain health decline in MS. This is a process that involves the ECS but is as yet not well understood.
The authors note that “By attenuating neural cell loss, cannabinoids contribute to delayed progression of experimental autoimmune encephalitis”. Further evidence of neuroprotective effects, including the “regulation of microglial activation”, the “inhibition of T-cell infiltration”, and “favouring and inhibiting Th2 and Th2 immune responses”, serve to highlight the important role in brain health and regulation.
Many neurodegenerative diseases are believed to be at least in part the result of a dysfunctional immune system. The important roles that CB1 and CB2 receptors play in regulating and modulating the immune system, through inflammation, controlling cell death and migration, and neurogenesis, shows that the ECS is an important area of study for the possible treatment of many different neurological disorders.
The authors even go so far as to state “cannabinoid-based treatment of MS may go beyond the palliation of clinical symptoms and could also target the etiological mechanisms responsible for the disorder”, something no other treatment has achieved.
The importance of the endocannabinoid system in brain health is a case well made here. Its role in normal brain functioning is explored and the potential of using the ECS as an avenue for therapy for currently untreatable neurological disorders like Alzheimer’s, Huntington’s, and MS, is particularly exciting.
The authors call for more research, especially in the area of NPs and the regulation of neurogenesis during development and neurodegenerative disorders.