Does Endocannabinoid Deficiency Cause Parkinson’s Disease?

Research analyzing the links between Parkinson’s disease and the endocannabinoid system has identified disruptions in the ECS. While this has been expanded, a deeper causal link between Parkinson’s disease and endocannabinoid deficiency has not been fully elucidated.

Beyond a dopamine deficiency

Parkinson’s disease is a movement disorder that affects dopamine and can cause neuron death. The disease is claimed to cause an increase in cannabinoid receptor activity, which knocks down dopamine and disrupts movement.

Different types of cannabinoid receptors are found throughout the body. Compounds in cannabis activate or alter the receptors that can release, protect, or moderate related transmitters.

Cannabinoid receptors are found throughout the brain but predominantly in the hippocampus (right), while Parkinson’s disease is fascinated by the basal ganglia (left). Photo courtesy of Sejnowski et al.

Endocannabinoids and dopamine

It is a highly short-sighted view to suggest that a solution can be found by shutting down cannabinoid receptor activity. In a larger picture, opposing interactions between the endocannabinoid system and dopamine can be found. Cannabinoid-1 receptors can either decrease, increase, or not affect dopamine (DA) depending on the mechanism and situation. Ultimately, unlike CB2 receptors, the relationship between dopamine and CB1 receptors is entirely indirect.

The endocannabinoid anandamide acts as a sentinel to prevent a flood of dopamine. And CB2 receptors inhibit dopamine receptors in the midbrain. Overall, however, endocannabinoids and their respective receptors balance neurotransmitters in the brain and body. With a disturbed ECS, however, the balancing act breaks down and can become problematic. At least that’s a link between endocannabinoid deficiency and Parkinson’s disease. But what actually breaks the system?

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 could directly affect the synthesis of endocannabinoids as well as the function of cannabinoid receptors. Therefore, alpha-synuclein can disrupt endocannabinoid function as an important and direct symptom of Parkinson’s disease.

Unfortunately, the exact mechanism behind certain causes has yet to be elucidated in research. Against this background, GTP binding is a key advantage for CB1 receptor signaling during Parkinson’s disease. And out of 60 known GTPases, two of the protein messengers are known to support critical mechanisms in CB2 receptor function. In addition, GTPases are severely disrupted during Parkinson’s disease. This author therefore proposes that specific proteins (Rab-GTPs) are involved in endocannabinoid deficiency during Parkinson’s disease.

Let us know in the comments if you have Parkinson’s or are close to someone who has found relief from medicinal cannabis. And read this story to learn more about endocannabinoid deficiency during brain injury.

Sources

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