Tuesday, November 22, 2022

Cannabinoids And Parkinson’s Disease

Heres How And Why It Works:

Cannabis and Parkinson’s Disease
  • Cannabis affects the ECS directly. The ECS regulates the interaction between the mind and the body. It affects the nervous system, organ function, and even the immune system. It works to maintain homeostasis, a term which describes the state of balance of the internal environment.
  • Parkinsons disease has a negative effect on the ECS. Cannabinoid receptors are located in the brains basal ganglia. Depletion of dopamine due to Parkinsons causes a weakening of the basal ganglia. This takes a cruel toll on the movement and mobility of a person with Parkinsons.
  • This particular region of the nervous system is filled with CB1 receptors. CB1 receptors are G-proteins. Cannabinoids such as cannabidiol and tetrahydrocannabinol bind to these receptors. This binding helps alleviate symptoms associated with dopamine deficiency.
  • Re-regulation of these functions is made possible with the binding of CBD to the CB1 receptors. This can also jump-start the body into making good use of its own cannabinoids.
  • Cannabinoids do not just promote healthy function of the brain. They are known to offer neuroprotective properties, potentially safeguarding the neurons against aging and disease.
  • Protection of the neuron is vital to dopamine protection. One of the early signs of Parkinsons disease is damage to the neurons. CBD oil may be able to assist in combating neural damage, regulate the production of dopamine, and inhibit the progression of Parkinsons disease.

Effects Of Cannabinoid Receptor 2 Receptors Stimulation On Neuroinflammation

Neuroinflammation is an important factor in the development and progression of disease in patients with PD. An over-activated inflammatory response leads to the death of dopaminergic neurons, and glial cells play an important role in the regulation of neuroinflammation . Microglia in the substantia nigra of the brain are abnormally activated in patients with PD .

Another group also found that treatment of nigrostriatal tyrosine hydroxylase-positive neurons with the CB2 receptor agonist JWH-015 attenuated MPTP-induced pro-inflammatory effects and reduced microglial activation in a PD model . Later studies have further revealed that JWH-015 causes a decrease in NF-B activity in LPS-activated BV-2 cells, thus exerting a neuroprotective effect . However, this inhibition could not be reversed by CB2 or CB1 antagonists, suggesting that the specific role of CB2 receptors requires further investigation.

Does Medical Cannabis Help Parkinsons

Medical marijuana has anti-inflammatory and antioxidant properties, and research has shown this can help prevent neuron damage. This is essential with Parkinsons since the inflammation can be responsible for causing damage to brain neurons that produce dopamine. Medical marijuana treatments may be able to slow some of the neuron damage in the brain and slow down the advancement of Parkinsons.

Other benefits of medical cannabis can include pain management that can help with problems such as sleeping and nausea. Florida medical marijuana may be able to help people with Parkinsons enjoy more natural movement since it contains muscle-relaxing properties.

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What Types Of Positive Effects In Medical Cannabis Use Have You Observed

As already discussed, the most striking effect is on sleep, and in general, cannabis could be considered a quality-of-life drug. The mild mood-enhancing, anxiety-lifting, sleep-promoting, calming, relaxing, and euphoric effects can be achieved with a low dose of THC, decreasing the chances for impairment, either cognitively or physically.

Any Advice For People With Parkinsons Considering Medical Cannabis Use

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In a perfect world, you would be able to discuss using medical cannabis with your doctor. However, due to the unusual situation of cannabis being understudied while widely used as a medicine, medical professionals may not feel prepared to provide advice on such use.

It is important to be open with your doctor should you decide to use cannabis, however, so that they can be helpful for helping to monitor any negative side effects or potential for drug-drug interactions. There is a plethora of experts who are giving advice on using cannabis. Some are healthcare professionals and some are not. Be wary of whom you get advice from. The best advice on how to employ and dose cannabis will come from someone who has a lot of experience working with PPD, as well as a strong background in cannabis science.

Be wary of what you read on the internet as it can be difficult to separate fact from marketing claims about what can be expected from cannabis use. The research on cannabis in PPD is very scant.

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How Does Medical Marijuana Affect The Body

Marijuana affects the body through neurotransmitters, which are the chemical messengers of the nervous system.

Various factors can stimulate neurotransmitter activity, initiating a set of physiological responses. In cannabis, it is mainly THC or CBD binding to endocannabinoid receptors that produce new physiological reactions in the body.

The endocannabinoid system is one of the most important neurotransmitter systems in the body. It utilizes cannabinoid receptors located throughout the central nervous system and peripheral nervous system . Cannabis works to turn on endocannabinoid neurotransmitters through activity at these receptors.

Results Of The Database

From a total of 228 identified articles, 114 were excluded as duplicates, 27 were excluded after title and abstract screening because they were not related to the subject . 88 articles remained for full-text review. No further relevant citations were found from weekly electronic database updates up to November 1, 2019. Finally, 14 of the 87 studies were included in this systematic review .

We could not perform a meta-analysis due to the high variability of

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Basal Ganglial Circuitry In Pd And Signaling Of Endocannabinoids

Figure 1

Basal ganglial circuitry in Parkinsons disease and tentative cannabinoid targets to improve motor disability in PD. Progressive loss of dopaminergic innervation in PD causes overactivity of the indirect pathway, resulting in excess glutamatergic drive to the GPi and SNpr and diminished activity of the inhibitory GABAergic direct pathway, further disinhibiting the activity of the GPi and SNpr. As output nuclei use the inhibitory neurotransmitter GABA, this amplified basal ganglia output leads to extreme inhibition of the motor thalamus which acts as a brake on motor activity thus, resulting in the onset of parkinsonian syndrome. The neural circuitry above depicts various possible cannabinoid- based targets that can be used to mitigate the symptoms observed in PD. Abbreviations: CB1, cannabinoid receptor 1 TRPV1, transient receptor potential vanilloid 1 GPe, external segment of the globus pallidus GPi, internal segment of the globus pallidus SNpc, substantia nigra pars compacta SNpr, substantia nigra pars reticulata STN, subthalamic nucleus GABA, gamma-aminobutyric acid.

Does Medical Cannabis Reduce Parkinsons Symptoms

Psychosis in Parkinson disease triggered by synthetic cannabinoid

Parkinsons disease is largely characterised by a difficulty in maintaining fluidity of movement. The two ways this main symptom presents is with hypokinesia or dyskinesia. For those experiencing hypokinesia, movement can slow to the point that patients can have difficulty initiating movement or feel as though their bodies are frozen.

Patients that experience dyskinesia often present with tremor, irregular or clunky movements due to dysfunction in signalling related to motor skills. Dyskinesia can also occur as a side effect of conventional Parkinsons treatments. While conventional medications have proven to be effective for a large portion of patients, there are others who suffer from aggressive forms of Parkinsons or dont tolerate standard pharmaceuticals. In these cases, medicinal cannabis treatments may provide a viable alternative.

Changes to parts of the brain that control movement, as well as the lack of dopamine, can also lead to mood disturbance, muscle rigidity, pain, loss of weight and changes to appetite. Medical cannabis has been researched for its effects on some of the key symptoms of Parkinsons disease.

In cases where pharmaceutical medications fail to reduce symptoms related to movement, mood or other neurological manifestation, medical cannabis may have a role to play. However, further investigation is required as the treatment can illicit side effects in some patients, while for others, the therapy may not yield any benefit.

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What Is Medical Marijuana

Medical marijuana is cannabis that’s prescribed by a physician to treat or provide relief for a medical condition.

There are around 400 chemicals in the cannabis plant, and more than 60 of them are referred to as cannabinoids. The high marijuana users get is primarily due to the most psychoactive cannabinoid in the plant called tetrahydrocannabinol, or THC.

Cannabinol, or CBD, is the other cannabinoid, which is used in medical marijuana. CBD does not cause a high when taken alone and, in fact, moderates the psychoactive effects. Research is being done to determine how medical marijuana can help treat or relieve symptoms of various diseases, including Parkinson’s disease.

Cannabinoids In Parkinson’s Disease

Parkinsons disease is aprogressive neurodegenerative disorder characterized by tremor, rigidity, and bradykinesia, or slowness of movement, and sometimes postural instability.

The bodys endocannabinoid system, part of our onboard neural signaling network ,has emerged as a potential therapeutic target forthe treatment of this disease.

This is based on a number of lines of evidence, including the dense localization of endocannabinoid neural receptor sites in brain regions involved in the control of movement and signs of dysregulation of the endocannabinoid system in human Parkinsons patients. Pharmacological modulation could well represent a new therapeutic tool. Studies in animal models are supportive so far, suggesting that drug development may offer benefits specifically in motor symptoms, neuroinflammation, and neuroprotection.

Evidence implicating the endocannabinoid system

There are two known endocannabinoid receptors. They are spoken of as CB1 and CB2. It is the latter which seems of promise, the site most associated in animal models with mediation of neurodegeneration, in which dying neurons activate microglia, which in turn elicits infiltration of macrophages and generates proinflammatory factors that kill further neurons. Evidence shows that activating microglial CB2 receptors can suppress microglial activity and reduce their downstream neurotoxicity, and as well prevent BBB leakage and protect against oxidative stress.

Toward a therapeutic strategy

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Research Focused On Proprietary Cannabis Technology

The Unlokt technology packs cannabis within a natural protein that bypasses the liver and shuttles the cannabis directly into the bodys circulation, which protects the cannabinoids and terpenes and allows them to be released and absorbed into the bloodstream in their entirety. The process allows the body to receive the intended amount of cannabinoids to produce the desired effect. Day Three Labs says that the delivery method is safe and offers predictable, functional effects for consumers and patients. The company believes the innovation will soon replace emulsion-based cannabinoid delivery systems used by cannabis edibles manufacturers across the industry.

Day Three Labs’ Unlokt technology is used to manufacture cannabis gummies from Olio.

Courtesy of Olio

Unlokt is a significant leap in technology that will disrupt traditional research and delivery of cannabinoid compounds and beyond, said Josh Rubin, co-founder and CEO of Day Three Labs. Utilizing a groundbreaking technology like Unlokt in the adult-use market is revolutionary and game-changing, and creates incredibly enjoyable products, but it only scratches the surface of what this technology is capable of. Our work with CanNegev is just the beginning of the technological advances we are bringing to this fast-growing industry with the hope of eradicating previously untreatable illnesses and conditions and bringing solutions to the cannabis industry that are safer, more efficacious and efficient.

Do You Recommend A Particular Route Of Delivery For Cannabis

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Inhalation is for those who need rapid effects, while taking a cannabis product orally will have much longer-lasting effects. Administration and dose are highly variable and dependent on many things, including considering drug interactions and existing balance issues, hypotension, dizziness, and cognitive function. The best advice will come from a medical provider who is skilled in the use of medical cannabis. Beware of information coming from dispensary personnel as they may be biased or not well informed about cannabis for medical use.

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Effect Of Cannabinoid Receptor 2 Receptors Stimulation On Neuronal Function

CB2 receptor activation also reduces the number of myeloperoxidase-producing astrocytes and increases antioxidant enzyme activity, thereby reducing the level of excessive oxidation in animal models of PD . And some cannabinoids have intrinsic structural antioxidant properties that contribute to their effectiveness as antioxidants . In addition, the CB2 receptor agonist Hu-308 has been found to attenuate the excitotoxicity induced by quinolinic acid injections .

CB2 receptors are also thought to affect the proliferation of neural progenitor cells . The use of the CB2 receptor agonist Hu-308 activates the PI3K/Akt/mTORC1 pathway, exerting a pro-proliferative effect on neuronal cells . In addition, CB2 receptors have been found in neural stem cells and can regulate the proliferation of neural precursor cells . It has also been found that activation of these CB2 receptors is also beneficial in alleviating the decrease in neurogenesis induced by age, as neuronal cell proliferation and partial restoration of neurogenesis levels occurred in the brains of aged animals after treatment with the CB2 receptor agonist Win-55,212-2 . Furthermore, CB2 receptors facilitate the repair of brain damage by promoting neuroblast proliferation, formation of new neurons, and repair of damaged areas .

Role Of Cannabinoid Receptor 2 Receptors In Parkinsons Disease

CB2 receptor is the second cannabinoid receptor that is discovered in humans . Studies have shown that CB2 receptors are distributed in neurons in the cortex, striatum, amygdala, hippocampus, and VTA . Therefore, activation of CB2 receptors could influence the progression of PD by regulating neurotransmission and neuronal function. Furthermore, some findings have shown that in the brain, CB2 receptors are abundantly distributed in activated astrocytes and microglia . Thus, they have a crucial role in regulating neuroinflammation .

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How Thc And Cbd Work

Cannabinoids from cannabis activate the ECS by binding to endocannabinoid receptors throughout the brain and body. The two most affected by cannabis are:

  • CB1 receptors: Found in the brain in high levels, they are responsible for marijuanas psychoactive properties, or the high effect.
  • CB2 receptors: Found throughout the body, they affect pain levels and inflammation.

THC strongly activates CB1 receptors, triggering a feeling of euphoria. This activation also increases blood flow to the prefrontal cortex of the brain, which is the area that controls the ability to focus, as well as our motor skills, attention, memory, and decision-making abilities.

THC also interacts with CB2 receptors, providing added analgesic , muscle relaxing, and antiemetic effects .

CBD activates both CB1 and CB2 receptors, although less strongly than THC. Although its CB1 and CB2 receptor activation does not produce a high, it has been shown to interact with additional receptors in the body and have calming and anti-inflammatory effects. For this reason, CBD has been used to treat pain, anxiety, and seizures.

The Pharmacology Of Cannabis

Medical Marijuana and Parkinson’s Part 3 of 3

The two primary components of marijuana are delta-9-tetrahydrocannibinol and cannabidiol . THC and CBD act on the cannabinoid receptors type 1 and type 2 , which are primarily found throughout the nervous system and on cells of the immune system. The way that THC and CBD acts on these two receptors is different and may help explain the different effects mediated by each of these compounds. For example, THC is the psychoactive component of marijuana and causes alterations in perception and mood. CBD, on the other hand, can reduce anxiety and may have anti-inflammatory properties.

The various compounds present in different marijuana plants and their variable effects on the CB1 and CB2 receptors make cannabis studies difficult to conduct. When researchers study the effects of a medication, dosages are controlled and often set to a specific number of milligrams. When testing medical marijuana, the dosage administered can vary dramatically depending on the plant and method of administration.

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Using Cbd For Treating Parkinsons Disease Symptoms

People with PD are already using CBD in various forms for all sorts of symptoms of PD including insomnia, anxiety, tremor, dystonia and pain.

Without clinical trial data however, we do not know whether CBD is safe and effective for a particular symptom, and if it is, what CBD formulation and dosage is best to be used for a particular symptom.

We also dont know the side effect profile of CBD in people with PD. At baseline, people with PD may have various non-motor symptoms that may make them more prone to side effects from CBD, including fatigue and nausea.

If you would like to try CBD for one of your PD symptoms, have a conversation with your movement disorders specialist about it. Your doctor may be willing to oversee your trying it, or may feel that it is too risky for you without evidence that it will help. At the very least, he/she can make sure that there are no drug interactions between CBD and anything else that you take and discuss with you any potential side effects that you need to be aware of.

Colorado Company To Research Cannabis As A Treatment For Parkinsons Disease

Colorado-based Day Three Labs announced this week that the worlds first government-sponsored cannabis technology incubator will fund the companys research into using cannabis as a treatment for Parkinsons disease.

Day Three Labs is a cannabinoid consumer products ingredient manufacturer specializing in the development and commercialization of novel cannabis products with its headquarters in Denver and a research facility in Israel, where regulations make studying cannabis far easier than in the United States. The firm is the only company to have passed the first phase of the CanNegev program, a cannabis technology incubator that receives funding from the Israeli government.

Colorado-based Day Three Labs announced this week that it has received funding from Israeli cannabis … technology incubator CanNegev to study cannabis as a treatment for the symptoms of Parkinson’s disease.

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Research shows that cannabis has the ability to ease Parkinsons symptoms in patients, but to date, no one has been able to decipher the exact combination of cannabinoids and terpenes for a consistent, reliable, and repeatable remedy, Dr. Shimon Lecht, chief innovation officer at Day Three Labs, said in a statement from the company on Monday.

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