Cannabinoids & Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disease and its characteristic is the progressive degeneration of dopaminergic neurons within the substantia nigra (SN) of the midbrain. Aka, Parkinson's disease is a brain disorder that leads to shaking, stiffness, and difficulty with walking, balance, and coordination. Parkinson's symptoms usually begin gradually and get worse over time. As the disease progresses, people may have difficulty walking and talking.

There is hardly any clinically proven efficient therapeutics for its cure in several recent preclinical advances proposed to treat PD. But, recent studies have found that the endocannabinoid signaling system, in particular the CB1 and CB2 receptors, have a significant regulatory function in basal ganglia which is directly involved in the pathogenesis of PD. Therefore, cannabinoids are adding significantly new insights into the biochemical interactions between the endocannabinoid system and other signaling pathways, which may help develop new pharmacological strategies used to combat PD.

Factors of the endocannabinoid system (ECS) are abundantly expressed in the neural circuits of basal ganglia, where they interact interactively with glutamatergic, γ-aminobutyric acid-ergic (GABAergic), and dopaminergic signaling systems.

Signalling at CB1 cannabinoid receptors plays a key role in the control of movement in health and disease. In recent years, an increased understanding of the physiological role of transmission at CB1 receptors throughout the basal ganglia circuitry has led to the identification of novel therapeutic approaches to both the symptoms of Parkinson’s disease and the side effects of current anti-parkinsonian therapies, especially L3, 4 dihydroxyphenylalamine (levodopa)-induced dyskinesia.

Levodopa-induced dyskinesia (LID) is a form of dyskinesia associated with levodopa (l-DOPA), used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis. In the context of Parkinson's disease (PD), dyskinesia is often the result of long-term dopamine therapy.

Thus, because activation of basal ganglia, CB1 receptors can modulate neurotransmission and contribute to synaptic plasticity in a manner similar to that described in other brain regions, it also appears that endocannabinoids might modulate cell–cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types.

Synaptic plasticity is change that occurs at synapses, the junctions between neurons that allow them to communicate.

Although preclinical studies on PD are promising, the use of cannabinoids at the clinical level has not been thoroughly studied and we must ask why? We need to have studies that both evaluated the available evidence, as well as review the involvement of ECS in etiologies, symptoms and treatments related to PD.

Since CB1 and CB2 receptors are the two main receptors of endocannabinoid system, a focus on the therapeutic role of these CB1 and CB2 receptors in PD is essential, is it not? Why are there only limited studies that try to determine future success in correlation between the potential therapeutic benefits of the ECS in the treatment of PD, that will ultimately open up new strategies and ideas for the treatment of PD?

The limited research avail, there are hopefuls for those of us that look towards cannabinoids to combat PD - a recent studies in animal models and in the clinic suggest that CB1 receptor antagonists could prove useful in the treatment of parkinsonian symptoms and levodopa-induced dyskinesia, whereas CB1 receptor agonists could have value in reducing levodopa-induced dyskinesia. So again, we are hopeful for the future regarding cannabinoid relief regarding Parkinson's Disease.

Highlights:

• The relationship between the endocannabinoid system and 
  Parkinson's disease (PD) is expounded.
• CB1 and CB2 receptors participate in multiple pathogenesis of 
  PD.
• The agonists or antagonists of CB1 and CB2 receptors are 
  promising in the treatment of PD.