Pathophysiology of Parkinson’s disease

Cannabidiol has long been considered a potential alternative therapy for the treatment of neurodegenerative diseases and movement disorders. Cannabis sativa extract has been used for centuries in the management of seizure disorders at a time when little scientific explanation exists for its actions on the central nervous system. Currently, research inquiries have explained the role of endocannabinoids and plant-derived cannabinoids on the endocannabinoid system. These agents work on the cannabinoid receptors and influence the system and modulate the body’s pain response, appetite stimulation, regulate memory formation, glucose metabolism, cell-to-cell signaling, and inflammatory response. 

Parkinson’s disease (PD) is a common neurodegenerative disease affecting about two people per 1000 individuals with a slowly rising incidence currently at 1% of the population. Current data reports estimate the global burden of Parkinson’s disease to be around nine million cases by the year 2030. PD results due to loss of dopaminergic neurons in the substantia nigra—a basal ganglia structure in the midbrain with a dopaminergic nucleus modulating motor movement. The degeneration of these neurons is a slow process with a cumulative effect occurring after a few years.  Continuous loss of dopaminergic neurons causes secondary morphological changes in the basal ganglia—density of the dendritic spine reduces and sensitivity of the dopamine receptors if affected. 

In patients with this disease, a confirmed diagnosis is made by examining for a triad of motor symptoms, including rigidity, tremor, and bradykinesia associated with postural instabilities. Motor symptoms develop as the disease progresses with the non-motor symptoms appearing at the later stages. Motor symptoms appearing at the early stages of PD include pain, fatigue, cognitive impairment, sleep disorders, autonomic dysfunction, and impaired olfactory ability. Non-motor symptoms presented by these patients include depression, anxiety, slowing of thought, memory difficulties, delusions, and personality changes. 

 

CBD in the management of Parkinson’s disease

Suggestions on the potential benefits of managing Parkinson’s disease with cannabidiol is based on the extensive function of the endocannabinoids and the endocannabinoid system (ECS) on the human body. The cannabinoid receptors are widely distributed in the basal ganglia, the brain’s mesocorticolimbic system, the spinal cord, peripheral neurons, immune-modulating cells, vascular elements, and the microglia. To explain a possible therapeutic approach, there is a need to establish a relationship between dopamine and the cannabinoid receptors. 

In 2009, the British Journal of Pharmacology published a medical review focused on examining the endocannabinoid system as a target for the treatment of motor dysfunctions. As reported by the investigators, extensive biochemical and pharmacological studies have demonstrated that the activation or inhibition of the cannabinoid system is associated with important motor responses that are maintained or enhanced in cases of malfunctions or neuronal degeneration. Further studies have revealed that activation of the ECS is associated with motor inhibition.

 

CBD and Parkinson's Disease

 

Suggested symptom improvement in Parkinson’s disease

  • Research suggests CBD inhibits the degradation of dopaminergic neurons

Reduction in the rate of dopaminergic neuron loss is perhaps the most important benefit of CBD in the management of Parkinson’s disease. Since dopaminergic neuronal degeneration is the main pathophysiological explanation for the onset of Parkinson’s disease, experimental models have been developed to examine the effects of CBD isolates on degeneration reduction. In 2005, the Journal of Neurobiology of Disease reported a study aimed at studying the neuroprotective effects of CBD on toxin-induced models of PD. Injection of the toxin 6-hydrodopamine into the medial forebrain promoted neuronal degeneration. However, treatment with CBD during a two-week period before toxin injection prevents damage to these neurons.  

  • Research suggests CBD improves psychotic symptoms of Parkinson’s disease

Patients with psychosis are known to have a significant level of anandamide—and endocannabinoid in the blood and cerebrospinal fluid. There are also numerous reports of increased expression of cannabinoid one receptors (CB1) on the peripheral immune cells. These observations prompted studies into the possible role of the ECS in psychosis. 

In 2008, the report of an open-label pilot study investigating the potentials of cannabidiol in the treatment of psychosis in PD was published by the Journal of Psychopharmacology. Using six consecutive outpatients with a confirmed diagnosis of PD, it was observed that the psychotic symptoms evaluated by the Brief Psychiatric Rating Scale showed a significant decrease under CBD treatment. Preliminary data from the study suggests that CBD is effective, safe, and well-tolerated in the management of psychosis in PD. 

  • Research suggests CBD improves complex sleep-related disorders of Parkinson’s disease

Sleep disorders are common non-motor symptoms of PD. In advanced stages of PD, these disorders reduce the quality of life of these patients and increase the risk of symptom complications. Sleep disorders commonly reported include insomnia, restless legs syndrome, REM-sleep behavior disorder, and excessive daytime sleepiness. 

Nocturnal akinesia, early-morning dystonia, cramps, and tremors are considered the main factors responsible for sleep disorders in PD.  The potential benefit of CBD in eliminating these disorders was not confirmed until the medical journal Clinical Pharmacology and Therapeutics published a report on the relationship between cannabidiol and sleep disorders in PD. Case review assessment for this study indicated that all patients treated with CBD had a prompt and substantial reduction in the frequency of sleep disorders in PD. 

  • Research suggests CBD improves the prognosis of Parkinson’s disease

CBD explores the endocannabinoid system in patients with PD and produces many beneficial effects that cumulatively improve the prognosis of the disease. Though not significantly defined yet, there is numerous research evidence detailing the anxiolytic, antidepressant, and antipsychotic properties of CBD. These combined effects are believed to significantly improve the quality of life of these patients. A double-blind exploratory trial was conducted in 2014 to evaluate the effect of cannabidiol in the treatment of patients with Parkinson’s disease. The study published by the Journal of Psychopharmacology selected 21 PD patients without dementia or comorbid psychiatric conditions. Following a six weeks’ treatment duration with CBD, result findings suggest that CBD improves the quality of life measures in patients with no psychiatric comorbidities. 

CBD has also been proven by different medical researchers to inhibit the painful sensation in PD patients. There are also reports of CBD use as an alternative therapy in the management of fatigue and slow movement as the condition progresses. 

 

REFERENCES

Anthony Tribunella

Having experienced the benefits of CBD first hand when it was starting to gain popularity, Anthony decided to spend his working life championing it to the public and his peers in the wider CBD community. As a CBD innovator himself, Anthony likes to remain at the leading edge of scientific and product development to ensure that the potential of CBD has every chance of being fully realized.

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