Thanks to the discovery of the endocannabinoid system, today’s researchers have a significantly better understanding of how chemicals in the brain interact and communicate. They also have a better understanding of what happens when the body does not produce enough neurotransmitters to interact with their corresponding receptors.
Many researchers today credit the endocannabinoid system with maintaining the functions of homeostasis, the internal balance that living organisms need to survive. It’s the process of homeostasis that keep internal processes such as fluid balance, blood sugar levels, and temperature within an established range.
The messengers of the endocannabinoid system are called cannabinoids. The two main endocannabinoids that are produced in the body, anandamide and 2-AG (2-arachidonoylglycerol) are referred to as endocannabinoids because endo means within. The corresponding endocannabinoid receptors located throughout the body are simply named CB1 and CB2. CB1 receptors are found in their highest concentration within the brain and spinal cord. CB2 receptors are most often found within the peripheral nervous system and the immune system. Just a few of the many functions regulated by the endocannabinoid system include:
- Muscle movement
- Energy and metabolism
- Pain perception and inflammation
- Cardiovascular function
- Digestive processes
- Immune system function
- Moods and emotions
- Sleep and sleep cycles
The endocannabinoid system messengers interact with the endocannabinoid receptors to initiate a response from the brain. The nature of the response is determined by the chemical composition of the message received.
The Endocannabinoid System
Ideally, the body would produce all the cannabinoids necessary to keep this essential regulatory system functioning efficiently, but under the influence of illness, injury, or stress, the demand for endocannabinoids can exceed the supply, creating an endocannabinoid deficiency.
Many researchers today believe endocannabinoid deficiencies are to blame for many difficult-to-treat conditions including migraine, fibromyalgia, irritable bowel syndrome, and several neurodegenerative disorders, raising questions about the therapeutic potential of plant-based cannabinoids for Parkinson’s disease.
The receptors of the endocannabinoid system also respond to the plant-based cannabinoids in cannabis. The phytocannabinoids in cannabis mimic the effects of cannabinoids produced in the body, potentially alleviating the effects of endocannabinoids deficiencies. It didn’t take researchers long to discover that the phytocannabinoids in cannabis plants, particularly CBD (cannabidiol), also influence several non-endocannabinoid receptors, including:
- Dopamine Receptors
Dopamine is a neurotransmitter released by neurons to send signals to other nerve cells when a CB1 receptor is stimulated. The brain has several dopamine pathways that regulate muscle movement, behavior, cognition, and the perception of pleasure and pain. CBD is shown to increase the production of dopamine by activating the G-coupled protein receptor GPR6.
- GABA Receptors
Gamma-aminobutyric acid (GABA) is a neurotransmitter that blocks the impulses between nerve cells. When GABA receptors are activated by the neurotransmitter, the excitability between overactive nerve impulses is substantially reduced. It’s the effect on GABA receptors that may explain the interest in cannabis products for their potential to minimize the tremors associated with Parkinson’s disease.
CBD is also shown to be a potent antioxidant that researchers believe contribute to the neuroprotective properties of cannabis. Antioxidants could be particularly beneficial for those living with neurodegenerative disorders, including Parkinson’s disease. While preliminary reports are encouraging, it’s important to note that there is still a significant amount of research that needs to be done to assess the full risks, benefits, and clinical applications of cannabis use.
Parkinson’s & Cannabis
The many plant-based cannabinoids in cannabis, particularly the non-psychoactive cannabinoid CBD, are showing remarkable potential for influencing nervous system function. By interacting with key receptors throughout the body, CBD is shown to have analgesic, antiemetic, antispasmodic, anti-inflammatory, and neuroprotective properties. The mechanisms are not yet fully understood because of the multiple targets affected, but many experts believe the antioxidant and neuroprotective properties beneficial to those living with neurodegenerative movement disorders. While the therapeutic potential of medical marijuana is encouraging, initial investigations are showing mixed results. Consider the following examples:
- An open-label study of CBD was conducted on six Parkinson’s patients experiencing symptoms of parkinsonian psychosis. All six patients found psychotic symptoms improved, confirming the antipsychotic properties of CBD. The same results were reported in Parkinson’s patients experiencing REM behavior sleep disorders. At higher doses, CBD shows a trend to delay the progression of dystonia, involuntary muscle contraction.
- Investigators divided 21 Parkinson’s patients into three groups: a control group, a group treated with 75 mg of CBD per day, and a third group taking 300 mg per day. Participants were assessed one week before beginning the trial for motor symptoms, general symptoms, and perceived well being and quality of life. While the trial concluded with no significant differences in general symptoms, perceived well-being scores significantly improved for those taking CBD. While the study suggests that CBD may have the potential to improve quality of life for those living with Parkinson’s disease, investigators cautioned that additional studies with a larger sample would be necessary before any determination could be made.
- Over a 31-day trial period, patients received an incrementally increasing daily dose of CBD, with the highest dose on the 17th day of the trial. Of the subjects who completed the trial, clinical rating scores decreased from 45.9 to 36.4, motor scores decreased from the initial 27.3 to 20.3, and mean rigidity scores decreased from 9.14 to 6.29. Data also suggested that CBD reduced irritability and minimized pain.
When viewing research and reports on the therapeutic potential of cannabis, it’s important to keep in mind that there are two distinctly different sources of CBD, marijuana and hemp. The plants are classified by their THC content. While THC (tetrahydrocannabinol) causes a psychotropic effect, it is also shown to work similarly to CBD for alleviating muscle spasms and pain. Many find the combined effects of THC and CBD superior to the effects of CBD alone.
In a survey of 84 Parkinson’s patients using cannabis, more than 46 percent experienced mild to substantial improvement of their symptoms. The Parkinson’s Foundation notes that most medical marijuana trials provide test subjects with capsules, tinctures, or nasal sprays containing either a combination of CBD and THC or CBD isolate.
ECS Function and Movement Disorders
During their investigations, researchers have found functions of the endocannabinoid system altered in those living with several movement disorders, including Parkinson’s disease. Since cannabinoid receptors are found in particularly high numbers in areas of the brain controlling movement, researchers are focusing on the ability of plant-based cannabinoids to bind basal ganglia (and other) receptors to potentially modify the progression or ease the symptoms of the disease.
A significant number of studies have explored the role of cannabinoids, particularly the effects of CBD, which is shown to mimic the effects of the endocannabinoids produced in the body and initiate a response from the endocannabinoid receptors. It’s the interaction with the endocannabinoid receptors and several non-endocannabinoid receptors that explain the anti-inflammatory, analgesic, antiemetic, anxiolytic, antispasmodic, and neuroprotective properties of cannabis.
Research also suggests the effects of CBD are potentially enhanced by the additional cannabinoids found naturally in cannabis, including THC. The amplification of the combined effects of these additional, lesser known, cannabinoids is called the entourage effect.
While preliminary investigations suggest modulating cannabinoid signaling could significantly improve symptoms,13 trials have yielded mixed results. But patient surveys and anecdotal evidence still suggest that cannabis has the potential to benefit the motor and non-motor symptoms of Parkinson’s disease. Since cannabis products can interact with several medications, it’s important to consult a healthcare provider before using cannabis or hemp-derived products.
The symptoms of Parkinson’s disease normally start out mild and sometimes come and go unnoticed (it is estimated that one out of four cases is misdiagnosed). Also, the order in which symptoms develop, as well as their severity, differs from one individual to another. However, symptoms often begin on one side of the body or even in one limb. As the disease progresses, it eventually affects both sides, even if one side is still more affected than the other.
It is unlikely that a person with Parkinson’s will experience all the symptoms listed below at the same time, but the first three are the most common:
- Tremor – people with Parkinson’s report shaking, which usually begins in the hand or the arm and is more likely to occur when the limb is resting
- Slowness of movement (bradykinesia) – movements are much slower than normal, which makes even everyday tasks particularly difficult
- Muscle stiffness (rigidity) – tension in the muscles makes it hard to move around and even make facial expressions, which can lead to painful muscle cramps (dystonia). People with Parkinson’s therefore often develop a “Parkinsonian gait” with a leaning forward tendency and small quick steps
- Postural Instability – This often manifests as repeated falls, which can cause serious injuries
As a result of these symptoms or in addition to them, people with Parkinson’s can have a range of other physical and mental symptoms.
Because of their slowness and tremors, people with Parkinson’s tend to have problems maintaining balance, risking falls and injury. They might also experience dizziness, blurred vision or a fainting episode when trying to get up, due to a sudden drop in blood pressure.
Parkinson’s can also be painful for the nerves. A person with Parkinson’s might have unpleasant sensations like burning or numbness. On the other hand, Parkinson’s also causes a loss of the sense of smell (anosmia), sometimes even several years before the appearance of the other symptoms.
They may also experience sexual dysfunction, along with overproduction of saliva (drooling), excessive sweating (hyperhidrosis), and difficulty swallowing (dysphagia), which can lead to malnutrition and dehydration.
People with Parkinson’s often have problems sleeping (insomnia) that can lead to fatigue during the daytime. Sleep is often disturmed by frequent urination during the night (urinary incontinence), as well as constipation.
Cognitive and psychological symptoms
People with Parkinson’s sometimes show symptoms of depression and anxiety, as well as midlife obesity.
Other than that, Parkinson’s is known to cause cognitive impairment. This may manifest as memory problems and difficulty in managing activities that require planning skills. Dementia might also be observed as a group of symptoms that features more severe memory problems, personality changes and even paranoia and hallucinations (psychosis).
Parkinson’s disease leads to a loss of nerve cells in a part of the brain called the substantia nigra. This part of the brain is responsible for movement, so when cells stop producing dopamine, an important neurotransmitter, there can be a gradual loss of control over the body’s movements, causing slowness, stiffness, and tremors.
Scientists are not sure what causes the nerve cells to die. However, studies suggest that their death is a slow process. The first symptoms of Parkinson’s only occur when around 80 percent of the nerve cells in the substantia are have been lost.
Also, several risk factors might trigger Parkinson’s symptoms. These are:
- Environmental factors – there is a modest risk of developing Parkinson’s due to exposure to pesticides, and it is also possible to minimize the chances of having the disease by avoiding cigarettes.
- Genetics – people with a first-degree relative with Parkinson’s are 15 percent more likely to develop the condition. Also, a mutation in one of several specific genes has been detected in about 5-10% of people diagnosed with Parkinson’s, whereas in the unaffected population it is present in less than one percent
- The presence of Lewy bodies – these are clumps of specific substances within brain cells that are considered markers of Parkinson’s disease. Though it is not clear what role they plan in causing the disease, researchers believe that Lewy bodies hold an important clue to the cause of Parkinson’s
No test can confirm Parkinson’s disease, so a physician will base the diagnosis on the patient’s report of symptoms, as well as medical history and detailed physical examination.
For the most part, if a patient describes at least two of these main signs, the doctor may suspect the reason for them is Parkinson’s:
- Tremor or shaking
- Stiff limbs
- Slow movement
- Frequent falls (the injuries caused by the falls are sometimes the reason for the initial doctor visit)
- The focus of the symptoms on one side of the body
A doctor may ask the patient to try a medication called carbidopa-levodopa, which helps the brain producing dopamine, thus enabling the brain to better control the nervous system and, therefore, the movements of the body. If the symptoms get better after using the medication, this is an indicator that the patient has Parkinson’s disease.
Several tests thoroughly examine the body to detect the cause for the symptoms. These include:
- DaTscan – an imaging test that uses a small amount of a radioactive drug and a special scanner to see how much dopamine is present in the brain
- CT (computed tomography) – uses X-rays and computers to produce images of the inside of the body, including the brain
- MRI (magnetic resonance imaging) – produces images of the body using a large magnet, radio waves, and a computer to translate the data into images