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CBD and Parkinsons

 

In the history of cannabis there are some defining moments when the plant’s medicinal properties go mainstream. A recent Youtube video did just that when it showed Larry, a Parkinson’s patient, before and after ingesting a cannabis extract. The ‘before’ was a body rigid and rocked by tremors. Just a few minutes after taking a small amount of cannabis oil, the uncontrollable shaking calmed and Larry’s voice became steady.

Footage courtesy of Ride with Larry

It literally looked like a miracle, and is the kind of compelling anecdotal evidence that propels medicinal cannabis plant out of the shadows and into the public domain.

However, much is still to be learned about the plant’s mechanisms in treating Parkinson’s, and scientists are on the hunt to find out just which compounds hold the key to slowing down the disease and managing its symptoms. And as it happens, CBD (Cannabidiol) is at the front of the pack.

What is Parkinson’s Disease?

Classed as a neurodegenerative disease of the central nervous system, Parkinson’s affects roughly 6 million people worldwide, most of whom are over 60. No one knows why it begins. There could be a genetic predisposition, while exposure to pesticides and serious head injuries are also stated as possible causes. Symptoms come on slowly over time and are most commonly related to the motor system, such as shaking, rigidity, slowness of movement or shuffling. But they can also be accompanied by cognitive and emotional disturbances, as well as difficulties sleeping.

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Mobility and movement are first affected because brain cells in a part of the brain called the substantia nigra begin to die, reducing production of the neurotransmitter, dopamine. This alters signalling in the basal ganglia, the area of the brain responsible for movement, thus leading to the collection of motor related symptoms known collectively as Parkinsonism.

Parkinson’s is incurable, and current treatment (Levodopa) targets dopamine depletion, although as more neuronal damage occurs the drug eventually becomes ineffective, and can even worsen the uncontrollable movements (dyskinesia) in patients.

Patients turn to cannabis

It’s little wonder then that Parkinson’s sufferers and their families, desperate to slow down the course of the disease and ameliorate the life limiting symptoms, look towards other options. And while to some cannabis might seem like a medical wildcard, its use for the disease can be traced back to the 19th Century, where it was described in William Richard Gowers’s “Manual of Diseases of the Nervous System.”

Back then, very little was known about the chemical compounds in the plant. Indeed, it’s only in the last twenty years that scientists have really begun to understand how cannabis affects the body with the discovery of the endocannabinoid system – the homeostatic regulator comprising a network of receptors (CB1 and CB2) and cannabis-like chemicals, found predominantly in the brain, central nervous and immune system.

Endocannabinoid System and Parkinson’s Disease

One of the key roles of the endocannabinoid system (ECS) is regulating the lifespan of a cell, something vitally important in the central nervous system where brain cell loss is particularly difficult to overcome. Scientists have come to realise that in neurodegenerative disease, the ECS may even have a neuroprotective effect, as indicated by alterations in endocannabinoid levels and receptor expression. While these ECS changes are open to interpretation, the conclusion reached is that they reflect the body trying to mitigate against the neuronal damage occurring as a result of the disease.

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The area of the brain affected by Parkinson’s, the basal ganglia, has a high density of CB1 receptors and in experimental Parkinson’s models scientists have observed increased CB1 activity in the region. Greater CB2 receptor expression has also been noted in the brain’s glial cells, as well as an overall increase in endocannabinoid production. Researchers have already seen that botanical cannabinoids found in the cannabis plant can have a direct impact on the endocannabinoid system. It’s no surprise then that an exciting area of research into combating neurodegenerative disease is the use of cannabinoids as therapeutic tools.

Cannabinoids as neuroprotectants

While current Parkinson’s medication seeks to redress the depletion of dopamine, the main focus of current cannabinoid research is into the neuroprotective, antioxidant and anti-inflammatory properties of the plant. Even the US Federal Government has patented cannabinoids as neuroprotectants and antioxidants for the treatment of diseases of the central nervous system.

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THC, the most abundantly found cannabinoid in cannabis, binds perfectly with the CB1 receptor, eliciting a neuroprotective effect. However, despite some favourable preclinical studies showing the THC’s ability to reduce Parkinson’s related excitotoxicity, scientists now know that CB1 activation can actually worsen the motor symptoms associated with the disease, thus taking THC out of the running.

But, all is not lost, because other cannabinoids also have a uniquely multi-pronged approach to protecting our brain cells both through ECS receptor activation, but also non-endocannabinoid system mechanisms.

And this is where CBD comes to the fore.

CBD and Parkinson’s

CBD is generally a tricky cannabinoid to understand as it has poor binding affinity with endocannabinoid receptors. Much of its pharmacological effect comes from its interaction with other non-ECS receptors, as well as inhibiting the enzyme that metabolizes a key endocannabinoid in the body. CBD has also been shown to block CB1 receptor activity, making it of particular interest for Parkinson’s research.

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But it’s as a powerful antioxidant that CBD shows most promise. By scavenging the free radicals causing oxidative stress, commonly believed to be a precursor to Parksinson’s, it does so independently of any endocannabinoid signalling. In the paper, ‘Endocannabinoids and Neurodegenerative Disorders: Parkinson’s Disease, Huntington’s Chorea, Alzheimer’s Disease, and Others’, the authors describe how “CBD is no less active against the brain damage produced by altered glutamate homeostasis than CBs that do target the CB1 receptor or those targeting the CB2 receptor against local inflammatory events.”

Also of key importance is CBD’s anti-inflammatory action, which again occurs independently of the endocannabinoid system, and is most likely related to the nuclear receptors of the PPAR family.

Lesser known cannabinoids show promise

Reducing inflammation is fundamental in the fight to slow down the progression of Parkinson’s disease. Scientists know that activating the CB2 receptors helps to reduce inflammation in the body. So they have turned their attentions to the lesser known cannabinoid, THCV, which has the unique ability to activate the CB2 receptors while blocking CB1 receptors, as well as also being a powerful antioxidant.

study carried out on animal models of Parkinson’s disease at the Complutense University in Madrid found that administering THCV lessened motor inhibition, reduced brain cell damage from toxins and protected certain neurones. The authors concluded that THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.”

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So far, no clinical studies using THCV for Parkinson’s have been carried, but many researchers posit that the cannabinoid used alone, or alongside CBD could provide a valuable therapeutic tool in the future.

And while not exactly a cannabinoid, β-caryophyllene, a terpene found in cannabis and other aromatic spices such as cloves and black pepper, has been found to act like a cannabinoid by stimulating and upregulating the CB2 receptor. In a recent study entitled, ‘Cannabinoid Type 2 (CB2) Receptors Activation Protects against Oxidative Stress and Neuroinflammation Associated Dopaminergic Neurodegeneration in Rotenone Model of Parkinson’s Disease,’ it was found to have “the potential therapeutic efficacy to elicit significant neuroprotection by its anti-inflammatory and antioxidant activities mediated by activation of the CB2 receptors.”

Clinical trials

While preclinical studies on animal models show some promise for the neuroprotective potential of cannabinoids in Parkinson’s, so far clinical trials have failed to convince the medical community. Studies have targeted small numbers of patients, and most have been observational rather than the gold standard of the double blind placebo.

In a survey carried out in the Czech Republic on Parkinson’s patients, of the 25% who used cannabis, 46% reported some benefits to their condition. While in a small non-placebo study, patients’ movements were assessed 30 minutes after smoking cannabis with improvements in tremor, rigidity, bradykinesia (slowness of movement), pain and sleep being noted.

CBD has also been examined in a study aimed at assessing the cannabinoid’s effect on Parkinson’s related psychosis, which after four weeks was found to improve. In another study, CBD was also seen to aid eye movement sleep behavior disorder, a condition commonly experienced with Parkinson’s. However, in a 2014 double-blind trial in which 119 patients were given either a placebo, 75mg or 300mg of CBD, no significant changes were noted in motor symptoms or neuroprotective effects, although those taking 300mg CBD did report improvements in their quality of life.

The future

Despite Parkinson’s being a qualifying condition for medical cannabis in many states in the US, there’s still a lack of the sufficient clinical evidence needed to convince the mainstream medical profession.

However, one doctor has acquired a $1 million dollar grant to conduct a clinical trial at the University of Colorado School of Medicine to study the effects of CBD on Parkinson’s. Maureen Leehey MD will be using the GW Pharma CBD extract Epidiolex in a stage 1 open label trial to test its safety and tolerability.  This will hopefully be followed by a second stage crossover, double-blind, randomized controlled trial (RCT) with 50 subjects testing whether CBD not only helps with tremors, but also improves anxiety and psychosis, cognition, anxiety, sleep, daytime sleepiness, mood, fatigue, pain, impulsivity, restless legs syndrome and REM sleep behaviour disorder.

Finally, as the search continues for other novel approaches, it will surely only be a matter of time before a THCV and CBD extract also makes it to the trial stage, as the combination is already being explored for other indications such as diabetes and epilepsy.

So, it’s still early days in the field of cannabinoid research for Parkinson’s and other neurodegenerative diseases. But early results look promising, and as more clinical trials take place, perhaps science will eventually catch up with what many patients have already experienced firsthand.

Do you or a family member use CBD for your Parkinson’s symptoms? What has been your experience? Please tell us in the comments section below.