An exhaustive review came out in mid-2018 in the journal Brain Research Bulletin by Dr. Dwaipayan Sen and colleagues from Vellore Institute of Technology in India has proposed that targeting the endocannabinoid system (ECS) may lead to better treatment options for sufferers of Parkinson's Disease (PD). PD is the second most common neurodegenerative disorder next to Alzheimer's and it currently has no cure. Current treatments (L-DOPA, dopamine receptor agonists, etc.) are used to slow the disease progression, however, PD is still ultimately fatal.
Photo source: Shutterstock (used with permission)
PD is diagnosed by certain motor symptoms, such as resting tremor, rigidity, bradykinesia, and impaired posture or balance. Its symptomology is attributed to a loss of dopamine (DA) neurons in the substantia nigra (SN), a region part of the basal ganglia in the brain. Its etiology is unknown but factors such as environment, genetics, and general aging have been proposed. The loss of DA neurons in the SN results in striatal dopamine deficiency. Scientists have long known the important role these DA neurons play in initiating and controlling voluntary movements.
Dr. Sen and colleagues present a compelling argument for the role of the ECS in keeping this system working in as a homeostatic mechanism. The ECS plays homeostatic roles in many regions of the body, including the central nervous system. This is also true for the basal ganglia. The authors point out that there are several pieces of evidence to support a role for the ECS in maintaining appropriate DA release in the striatum for the proper coordination of movement.
First of all, in animal models of PD, destroying DA neurons in the SN and depleting the striatum's source of DA causes endocannabinoid (EC) levels to rise in the striatum. This enhancement of EC levels leads to motor impairments in mice similar to what is seen in PD patients. Another piece of evidence is the finding of EC receptors (e.g. CB1 and CB2) on neurons within the striatum, which lends credence to ECs role in modulating neural activity there.
Second of all, PD pathogenesis has been associated with many processes that can cause oxidative stress which could lead to cell death. For example, several genes have been implicated in PD. Mutations in these genes could promote mitochondrial dysfunction. This dysfunction can cause oxidative stress, which can lead to inflammation and eventual death of the cell.
Photo source: Shutterstock (used with permission)
The authors discuss the literature that shows an "anti-inflammatory" aspect of the ECS. The ECS has been shown to attenuate the inflammatory response in the body, acting as a kind of "counter-balance" the inflammatory chemicals being released. This neuroadaptive function is lost in PD. From looking at post-mortem tissue from the brains of PD patients, researchers found a four-fold increase in the expression of CB2 when compared to control samples. This increase could have occurred in response to the increase in overall EC levels. Whether or not this was a compensatory response or a contributor to the disease is unknown, however, the implication that the ECS is involved somehow in PD could point the direction to novel treatments.
Sources: Brain Research Bulletin, Neuroepidemiology, www.mayoclinic.org, Annals of Neurology, Journal of Neuroscience, Translational Neurodegeneration, TRENDS in Pharmacological Sciences
