Parkinson’s disease (idiopathic Parkinson syndrome) is the second most common neurodegenerative disease after Alzheimer’s disease. According to the German Parkinson Association, approximately 1% of people over 60 years of age in Germany are affected. However, the onset of the disease is usually preceded by decades of changes in the body. The risk of contracting the disease is estimated to be 2% for men and 1.3% for women.

So far, there is no cure for Parkinson’s disease. Medical treatment options are also limited. They serve to alleviate symptoms and to improve the quality of life of those affected. Various studies, and also experience reports of patients, show that the use of medical cannabis can be a complementary therapy option.

Parkinson’s disease: symptoms and causes

The neurological disease owes its name to the English physician James Parkinson, who in 1817 called it “Shaking Palsy” (shaking paralysis), although it is rather a progressive impoverishment of movement.

At the beginning of the disease, unclear symptoms appear which resemble a rheumatic disease. The first signs include unilateral muscle tension in the shoulder-arm region, digestive disorders, sudden sweating or fatigue. Sleep disturbances or a restless sleep with sleeping-talking or rowing with the arms can also be first signs.

In later stages, slight movement disorders, such as a changed gait pattern, occur. In addition, affected people bend forward and take small steps. The facial expressions also change and become more rigid, the hands begin to tremble at rest (rest tremor) and the voice becomes quieter.

These symptoms increase as the disease progresses. In particular, fine motor activities, such as buttoning up a piece of clothing, become problematic. In addition, those affected find it more difficult to coordinate movements and postural instability (lack of stability of the upright body posture) occurs.

In the advanced stage further symptoms are added:

  • Slowing down of movements
  • Muscle stiffening
  • Memory disorders
  • Visual and olfactory disorders
  • Constipation
  • Increased salivation
  • Changes in personality

In the late stages, Parkinson’s patients are so restricted that they need a wheelchair to move around. In the final stage of Parkinson’s disease, neither swallowing nor speaking is possible.

Causes are not clarified

To date, the causes are still unclear. It is assumed that patients suffer from a deficiency of the messenger substance dopamine, as the dopamine-containing nerve cells in the brain increasingly die during the course of the disease. However, the messenger substance dopamine is essential for the transmission of information from cell to cell, for example for movement.

Parkinson’s disease: What forms are there?

In addition to Parkinson’s disease, there are other forms of neurological disease:

  • Familial Parkinson’s syndrome is caused by a genetic mutation. The first signs usually appear at a young age.
  • If the nerve cells die off progressively as part of a neurodegenerative disease (e.g. Alzheimer’s), this can trigger the atypical Parkinson’s syndrome.
  • For secondary Parkinson’s syndrome, various drugs (e.g. antihypertensive drugs or neuroleptics) can be the trigger. Other triggers can include brain tumours, metabolic disorders (Wilson’s disease) or recurrent brain injuries (“Boxer’s Parkinson’s”).
  • In Lewy body dementia (Lewy body dementia or Lewy corpuscle dementia), protein deposits (Lewy corpuscles) form in the nerve cells. In older people, Lewy body dementia is the second most common neurodegenerative form of dementia after Alzheimer’s disease.

Parkinson’s disease: diagnosis and treatment

Parkinson’s patients show only unclear symptoms in the early stages, which makes diagnosis difficult. First indications can be given by imaging procedures such as positron emission tomography and a levodopa test (L-dopa test). Often, however, Parkinson’s disease is not diagnosed until a later stage of the disease.

A study from Juntendo University in Tokyo (1) is particularly interesting. The researchers investigated the serum levels of caffeine and caffeine metabolites in Parkinson’s patients and healthy people. They found that caffeine consumption in men could possibly reduce the risk of Parkinson’s disease. In addition, caffeine and caffeine metabolites could be new biomarkers for the detection of Parkinson’s disease.

Drug treatment for Parkinson’s disease

In order to compensate the lack of dopamine, Parkinson’s patients are often given various drugs, such as L-dopa preparations. The drugs MAO-B inhibitors and COMT inhibitors are used to reduce the breakdown of the messenger substance. In contrast, dopamine agonists can mimic a dopamine effect. It is also possible to use NMDA agonists in patients with excessive glutamate formation. These can inhibit the messenger substance glutamate. If the messenger substance acetylcholine is present in excess, anticholinergics can influence this.

Basically, the choice of medication depends on various factors such as age, the severity of symptoms and the severity of accompanying disorders. The problem with L-dopa therapy is that it is well tolerated in the first years of the disease, but cannot prevent the disease from progressing. Over time, the duration of the effect decreases and serious side effects such as cardiovascular disorders, extreme fatigue, stomach problems and psychological disorders can occur.

Medical cannabis for Parkinson’s disease

Various studies have shown that cannabis for medical purposes can alleviate motor disorders and non-motor disorders such as restlessness, tremor, sleep disturbances or anxiety that occur in the context of Parkinson’s disease. This is because cannabinoids from the cannabis plant, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), activate the CB1 receptors and CB2 receptors in the endocannabinoid system. Since the cannabinoid receptors also occur in the brain, the cannabinoids can exert their effect on the cell complex that is involved, among other things, in the regulation of motor skills.

Use of cannabis as medicine for dyskinesia

The majority of Parkinson’s patients suffer from dyskinesia, i.e. involuntary muscle movements and tremors. Patients then perform dancing movements of the hands and/or feet (chorea) or perform slow, twisted movements (athetosis). Persistent muscle contractions (dystonia) can also occur.

Various studies have already shown that medical cannabis can relieve dyskinesia, such as those conducted by researchers at the University of Manchester. Here the synthetic cannabinoid nabilone has been shown to reduce dyskinesia in Parkinson’s disease (2). Nabilone mimics THC and acts as a CB1 agonist.

Italian researchers at the University of Foggia came to the same conclusion and stated that medicinal cannabis could help to alleviate dyskinesias (3).

Cannabis substitute against dyskinesia in Parkinson’s syndrome

Australian researchers from the University of Technology Sydney published the results of their interesting study in 2019, in which they tested the cannabis substitute HU-308 in mice with Parkinson’s disease (4). This was just as effective as the active substance amantadine, a drug used to treat dyskinesia in the context of Parkinson’s disease. The simultaneous administration of amantadine and the cannabis substitute also proved to be effective. However, clinical studies on this are still lacking.

Parkinson’s disease: treatment with CBD

In recent years there has been an increasing medical interest in the therapeutic effects of the non-psychoactive cannabinoid cannabidiol (CBD). Various studies have shown that CBD can reduce symptoms such as restlessness, tremors, sleep disorders and anxiety. This cannabinoid can therefore also be used in the treatment of Parkinson’s disease.

Brazilian researchers at the University of Sao Paulo divided 21 patients into three groups. The first group took 75 milligrams of CBD every day, the second 300 milligrams and the third group received a placebo. Here a positive effect was shown and the quality of life of the patients improved. However, the researchers also emphasized that further research was needed (5).

The researchers also investigated the effects on REM sleep behavior disorder (RBD) in patients with Parkinson’s disease. Drug therapy with CBD reduced these Parkinson’s symptoms in the patients (6).

It is also interesting to note that cannabidiol has also been shown to have a presumed antipsychotic effect. This is because many patients in advanced stages of Parkinson’s disease display psychotic behaviour. The Brazilian researchers selected two women and four men with Parkinson’s syndrome who suffered from psychosis for a study (7).

Over a period of three months, the researchers administered a daily dose of 150 milligrams of CBD medication to the patients in addition to the other drugs. This was followed by evaluation using a psychiatric evaluation scale and the Parkinson’s disease psychosis questionnaire. A significant reduction in psychotic symptoms was shown under treatment.

Cannabidiol against motor disorders

With regard to motor symptoms, the preclinical studies are promising. However, the few studies with patients who were administered CBD did not show any improvement of these symptoms. However, previous research suggests that CBD may play a preventive rather than a therapeutic role in Parkinson’s disease (7).

The disease is often diagnosed after the first motor symptoms appear. By then, about 60% of the dopaminergic neurons may have died. The contradictory study results could be explained by the fact that CBD has only been administered in clinical trials at an advanced stage.

Unfortunately, the early diagnosis of the disease remains a major challenge, which makes the implementation of prevention strategies considerably more difficult. Presumably, the development of diagnostic criteria to detect the disease at an early stage could expand the application possibilities of CBD.

The molecular mechanisms associated with the improvement of motor disorders through CBD treatment may be diverse. There is evidence that this may depend on CBD effects on the 5-HT1A, CB1, CB2 and/or PPARγ receptors.

In addition, all movement disorders are always associated with oxidative stress and inflammation. Studies suggest that the non-psychoactive cannabinoid may have antioxidant and anti-inflammatory effects, both in vitro and in animal models of movement disorders.

Conclusion

Medical cannabis and also pure cannabidiol can relieve various ailments such as restlessness, anxiety, sleep disorders and tremors. The cannabinoid THC also seems to be able to reduce the involuntary movements (dyskinesias) that occur in Parkinson’s disease. CBD has also shown promise in preclinical studies. In clinical studies on patients, however, CBD did not show any improvement in symptoms.

(1) Juntendo University, Motoki Fujimaki et al., 2018, „Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease

(2) University of Manchester, Manchester, United Kingdom, Fox SH1 et al., 2002, „Stimulation of Cannabinoid Receptors Reduces Levodopa-Induced Dyskinesia in the MPTP-lesioned Nonhuman Primate Model of Parkinson’s Disease

(3) University of Foggia, Viale Luigi Pinto 1, 71100 Foggia, Italy, Maria Grazia Morgese et al., 2007,Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson’s disease: role of CB1 and TRPV1 receptors

University of Technology Sydney, 15 Broadway, Sydney, Australia, 2019, „Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia

(5) University of São Paulo, Ribeirão Preto, São Paulo, Brazil, 2014, „Effects of Cannabidiol in the Treatment of Patients With Parkinson’s Disease: An Exploratory Double-Blind Trial

(5) University of São Paulo, Ribeirão Preto, São Paulo, Brazil, 2009, „Cannabidiol for the Treatment of Psychosis in Parkinson’s Disease

(6) University of São Paulo, Ribeirão Preto, São Paulo, Brazil, 2014, „Cannabidiol Can Improve Complex Sleep-Related Behaviours Associated With Rapid Eye Movement Sleep Behaviour Disorder in Parkinson’s Disease Patients: A Case Series

(7) Federal University of São Paulo, São Paulo, Brazil, Fernanda F. Peres et al., 2018, „Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?