Does endocannabinoid deficiency cause Parkinson’s Disease?

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Research analyzing connections between Parkinson’s Disease and the endocannabinoid system has noted disruptions in the ECS. While this has been expanded upon, a deeper causative link between Parkinson’s Disease and an endocannabinoid deficiency has not been fully elucidated.

Beyond a dopamine deficiency

Parkinson’s Disease is a movement disorder that affects dopamine and can cause neurons to die. It’s been purported that the disease causes an uptick in cannabinoid receptor activity, which knocks down dopamine and disrupts movement.

Different types of cannabinoid receptors are located everywhere throughout the body. Compounds in cannabis activate or change the receptors, which can release, protect, or moderate related transmitters.

Cannabinoid receptors are located everywhere in the brain but are predominant in the hippocampus (right), whereas Parkinson’s Disease is fascinated in the basal ganglia (left). Photo courtesy of Sejnowski et al.

Endocannabinoids and dopamine

It is a highly short-sighted view to suspect that a solution can be found by turning down cannabinoid receptor activity. In a larger picture, contrasting interactions between the endocannabinoid system and dopamine can be found. Cannabinoid 1 receptors can either decrease, uptick, or do not affect dopamine (DA) depending on the mechanism and situation. At the end of the day, unlike with CB2 receptors, the relationship between dopamine and CB1 receptors is entirely indirect.

The endocannabinoid, anandamide, acts as a guardian to prevent a flood of dopamine. And CB2 receptors inhibit dopamine receptors in the midbrain. Yet, overall, endocannabinoids and their respective receptors balance neurotransmitters in the brain and body. In a disrupted ECS, however, the balancing act breaks down and can become problematic. At least, that is one connection between endocannabinoid deficiencies and Parkinson’s Disease. But what breaks the system in the first place?

Alpha-synuclein alters GTPases, which metabolize guanosine triphosphate (GTP). RNA synthesis, and ultimately the function of cannabinoid receptors, CB1 and CB2, are assisted by GTP. And while they inhibit motor function, CB receptors also facilitate neuroprotective properties.

Proteins at the root of a deficiency

Parkinson’s Disease is caused by the production of two proteins, beta-amyloid and alpha-synuclein. The latter of the two might directly affect the synthesis of endocannabinoids as well as the function of cannabinoid receptors. Therefore, alpha-synuclein can disrupt endocannabinoid function as a major and direct symptom of Parkinson’s Disease.

Unfortunately, however, the exact mechanism behind certain root causes has yet to be elucidated in the research. With that said, GTP binding is a critical asset for CB1 receptor signalling during Parkinson’s. And out of 60 known GTPases, two of the protein messengers are known to facilitate critical mechanisms in CB2 receptor function. Furthermore, GTPases are heavily disrupted during Parkinson’s Disease. This author, therefore, proposes that specific proteins (Rab GTPs) are involved in an endocannabinoid deficiency during Parkinson’s Disease.

Let us know in the comments if you have or are close to someone with Parkinson’s Disease that has found relief in medical cannabis. And read this story to learn more about endocannabinoid deficiencies during brain injury.

Sources

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  6. Lastres-Becker I, Cebeira M, de Ceballos M, Zeng B-Y, Jenner P, Ramos JA, et al. Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patients with Parkinson’s syndrome and of MPTP-treated marmosets. Eur J Neurosci. 2001a;14:1827–1832.
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