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Cannabidiol in Parkinson’s disease

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Parkinson’s disease (PD) is a common and complex neurological disorder that encompasses a range of clinical, epidemiological, and genetic subtypes. Loss of dopaminergic neurons in the substantia nigra leading to striatal dopamine depletion is the core mechanism underlying the cardinal motor features of PD. Although depletion of dopamine is the most notable neurotransmitter change in PD, other neurochemical changes occur and contribute to PD symptomatology. Many regions of the nervous system outside the basal ganglia are also involved in PD. The underlying molecular pathogenesis involves multiple pathways and mechanisms, such as α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation.

Although clinical diagnosis relies on the presence of cardinal motor features, PD is also associated with numerous non-motor symptoms that can be equally disabling than the motor symptoms or even more so. Drugs that enhance intracerebral dopamine concentrations or stimulate dopamine receptors remain the main treatment for motor symptoms. None of available treatments have proven to be neuroprotective or disease-modifying. Dopaminergic drugs are particularly effective during the early stages of the disease. However, PD invariably progresses, and long-term use of these medications may lead to reduced drug efficacy and the development of complications such as motor fluctuations and dyskinesias.

Unlike most of the motor features of PD, many non-motor symptoms do not respond to dopaminergic therapy, and some are indeed aggravated by them, with great impact on patient quality of life. The refractoriness of these symptoms to dopaminergic therapy implicates non-dopaminergic mechanisms. Therefore, current needs in the management of symptomatic patients with PD include dopamine-unresponsive axial motor impairments and non-motor symptoms, such as dementia, depression, anxiety, psychosis, and pain.

There is a clear need for therapies that target other pharmacological systems. A multimodal approach combining activity on dopaminergic as well as non-dopaminergic system would be very helpful and needs to be explored.

There has been interest in cannabidiol (CBD) as a treatment option for PD because of the identification of multiple potential targets of action in the CNS. CBD is one of the many cannabinoids identified in Cannabis sativa, being the second most abundant constituent after Δ9-tetrahydrocannabinol (THC). Unlike THC, CBD is non-psychoactive, and has been ascribed many potential medical benefits.

In this issue of the Brazilian Journal of Psychiatry, a research group from Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil, addressed animal and human clinical studies involving the use of CBD for PD.1 The authors discussed the biological bases for a potential effect of CBD in this setting, as well as preclinical and clinical studies of CBD in PD. The latter, all conducted by their group, are an open-label study,2 a case series,3 and a randomized controlled trial.4 The open-label pilot study was conducted with six PD patients with psychotic symptoms, lasting at least 3 months before study entry, that could not be controlled by reduction of antiparkinsonian medications.2 Oral CBD doses ranging from 150-400 mg/day, combined with classic antiparkinsonian agents, reduced psychotic symptoms evaluated by different scales (the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire), with no influence on cognitive and motor signs and no severe side effects. The second study was a case series of four PD patients with REM sleep behavior disorder (RBD).3 All had prompt, substantial, and persistent reductions in he frequency of RBD after CBD treatment. After drug discontinuation, the complex movements of RBD returned with baseline frequency and intensity. The third study was an exploratory double-blind trial of CBD versus placebo.4 Twenty-one PD patients without dementia or comorbid psychiatric conditions were assigned to three groups of seven subjects each who were treated with placebo, CBD 75 mg/day, or CBD 300 mg/day. Participants were assessed with respect to motor and general symptoms score (Unified Parkinson’s Disease Rating Scale [UPDRS]) and well-being and quality of life (Parkinson’s Disease Questionnaire [PDQ-39]). There were no differences across groups in motor score. However, the groups treated with CBD 300 mg/day had significantly different mean total scores in the PDQ-39. The authors point to a possible effect of CBD in improving measures related to quality of life in PD patients without psychiatric comorbidities.

All of these studies showed interesting results, but sample sizes were very small and the duration of follow-up was very short. The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD published in 2018 concluded that there was insufficient evidence to support the use of CBD for the treatment of PD at the time.5

It is vital to note that no conclusions can be drawn on the efficacy of CBD in this setting, as larger phase III and conclusive efficacy trials have not been conducted in PD. Double-blind, placebo-controlled, randomized trials with larger samples of patients with PD are needed to elucidate the possible effectiveness and mechanisms involved in the therapeutic potential of CBD in PD. Additionally, studies conducted specifically to evaluate the safety profile of CBD in patients with PD (including long-term safety), possible interactions with antiparkinsonian drugs, and possible side effects, as well as the therapeutic window for motor and non-motor PD symptoms, are also required.

Disclosure

CRR has been on the speakers’ bureau/advisory board and/or has acted as a consultant for UCB Biopharma S.A., Teva Farmacêutica, Roche Farmacêutica, and Medtronic.

Using CBD to Treat Parkinson’s Disease Symptoms

The benefits and research around CBD are still emerging

Colleen Travers writes about health, fitness, travel, parenting, and women’s lifestyle for various publications and brands.

Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.

Diana Apetauerova, MD, is board-certified in neurology with a subspecialty in movement disorders. She is an associate clinical professor of neurology at Tufts School of Medicine.

With the legalization of medical marijuana, many states are approving the use of it in a non-traditional way to treat the symptoms of certain conditions, including Parkinson’s disease. Marijuana has two major components to it—tetrahydrocannabinol (THC) and cannabidiol (CBD). Both may help with nausea and muscle pain or spasms, but unlike THC, CBD doesn’t give you the “high” feeling marijuana is most commonly known for. This makes it an enticing, natural way for many to help treat their Parkinson’s disease symptoms. What’s more, is that because CBD is a natural compound from the Cannabis sativa plant, using it may also leave you side effect-free, unlike many prescription medications.

Research

The body of research on using CBD for Parkinson’s disease symptoms is rapidly growing, as Parkinson’s disease affects 1% of the population over 60 years old.   Parkinson’s disease is a neurological condition, affecting the nervous system. Parts of the brain that produce dopamine, which is responsible for sending messages to the body in order to direct movement, become damaged or die. This results in tremors, muscle stiffness, the inability to use facial expressions, and trouble balancing.

In connection with Parkinson’s disease as well as other movement-related disorders, CBD may help improve motor skills. In one study published in Frontiers in Pharmacology CBD was shown to have a more preventative role in delaying abnormal movement symptoms in animal models of Parkinson’s.  

Since Parkinson’s disease can take some time to properly diagnose when the symptoms are already prevalent, using CBD once diagnosed may not offer much benefit. With early detection combined with the use of CBD together the possibility of reducing movement-related symptoms increases.

Those dealing with Parkinson’s disease may also have trouble sleeping due to REM sleep behavior disorder (RBD), a condition in which patients ‘act out’ their dreams while asleep. A study published in the Journal of Clinical Pharmacy and Therapeutics found that four patients with Parkinson’s disease who also suffered from RBD had a decrease of RBD symptoms during sleep with the use of CBD.

In some cases, people suffering from Parkinson’s disease may also have symptoms of psychosis, ranging in hallucinations to vivid dreams and illusions. Research has found that CBD may be able to help. In research out of University of São Paulo in Brazil, patients were given a dose of CBD starting out at 150 milligrams (mg) per day in addition to their current treatment plan of therapy for four weeks. The use of CBD showed no adverse effects, no impact on worsening motor function, and a decrease in their reported psychosis symptoms, meaning that not only can it help with the physical setbacks of Parkinson’s disease, it can also play a part in the cognitive challenges as well. This was however an older study and current clinical trial evidence to support the use of CBD is minimal.

More research out of Brazil suggests CBD can improve the overall quality of life of those with Parkinson’s disease. In a sample of 21 patients, those who were treated with 75 mg to 300 mg of CBD per day reported a significant increase in quality of life, though no significant differences were noted in motor and general symptoms or neuroprotective effects. This goes to show how much results can vary when it comes to the effects of CBD, requiring larger studies to be done in order to get more definitive answers to this treatment option.

Uses and Safety

Parkinson’s disease can impact cognitive function and memory, particularly in those whose symptoms progress to Parkinson’s disease dementia. Because of this, medical marijuana with both THC and CBD may not be recommended, as it can impair thinking and brain function even more so. CBD by itself may be a safer route.

CBD has been discovered as an effective way to help treat Parkinson’s disease symptoms because it interacts with two cannabinoid receptors in the body found on certain cells called CB1 and CB2. By interacting with one or both of these receptors, CBD may delay tremor development as well as have protective neurological benefits. But as seen with the above studies, there is no uniform approach or conclusion on this treatment method. This means that patients may react differently to using CBD, some having tremendous success while others seeing little difference. But regardless of whether or not CBD is an effective treatment option for you, you always need to consult your treating physician to make sure this treatment will not cause side effects.

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What can cause side effects is if a patient decides to mix medical marijuana with their treatment plan that consists of certain prescription medications. If you plan to use medical marijuana as opposed to CBD by itself, it’s smart to consult a healthcare provider or your pharmacist before you start mixing it in with other medications to make sure it’s safe for you.

Should You Use It?

While the research on CBD to treat Parkinson’s disease symptoms is largely inconclusive, its mild effect on patients as a whole makes it enticing to try in addition to an existing traditional treatment plan. Parkinson’s disease has no cure. But with prescription medication, therapy, and now perhaps the use of nontraditional options like CBD, patients may be able to experience less frequency and severity of symptoms that affect their motor skills.

If you’re interested in trying CBD for Parkinson’s disease, talk to your healthcare provider about it. They will be able to point you to the latest research and provide recommendations on how much you should take. They will also be able to monitor your progress with the rest of your care team in order to come to a conclusion if this is the right treatment plan for you.

Cannabis and Parkinson’s disease

This is the kind of post that can really get someone in quite a bit of trouble.

Both the legal kind of trouble and the social media type of trouble.

Given the online excitement surrounding a particular video that appeared on the internet last week, however, we thought that it would be useful to have a look at the research that has been done on the medicinal use of Cannabis and Parkinson’s disease.

In addition, we will assess the legal status regarding the medicinal use of Cannabis (in the UK at least).

Cannabis being grown for medicinal use. Source: BusinessWire

This week a video appeared online that caused a bit of interest (and hopefully not too many arrests) in the Parkinson’s community.

Here is the video in question:

The video was posted by Ian Frizell, a 55 year old man with early onset Parkinson’s disease. He has recently had deep brain stimulation (DBS) surgery to help control his tremors and he has also posted a video regarding that DBS surgery which people might find useful (Click here to see this).

In the video, Ian turns off his DBS stimulator and his tremors quickly become apparent. He then ‘self medicates’ with cannabis off camera and begins filming again some 20-30 minutes later to show the difference. The change with regards to his tremor are very clear and quite striking.

Here at the SoPD, we find the video very interesting, but we have two immediate questions:

  1. How is this reduction in tremors working?
  2. Would everyone experience the same effect?

We have previously seen many miraculous treatments online (such as coloured glasses controlling dyskinesias video from a few years ago) which have failed when tested under controlled conditions (the coloured glasses did not elicit any effect in the clinical setting – click here to read more). Some of these amazing results can simply be put down to the notorious placebo effect (we have previously discussed this in relation to Parkinson’s disease – click here to read the post), while others may vary on a person to person basis.

Thus, while we applaud Mr Frizell for sharing his finding with the Parkinson’s community, we are weary that the effect may not be applicable to everyone. For this reason, we have made a review of the scientific literature surrounding Cannabis and Parkinson’s disease.

What exactly is Cannabis?

Drawings of the Hemp plant, from Franz Eugen Köhler’s ‘Medizinal-Pflantzen’. Source: Wikipedia

Cannabis (also known as marijuana) is a family of flowering plants that can be found in three types: sativa, indica, and ruderalis. Cannabis is widely used as a recreational drug, behind only alcohol, caffeine and tobacco in its usage. It typically consumed as dried flower buds (marijuana), as a resin (hashish), or as various extracts which are collectively known as hashish oil.

While the three varieties of cannabis (sativa, indica, and ruderalis) may look very similar, pharmacologically they have very different properties. Cannabis sativa is often reported to cause a “spacey” or heady feeling, while Cannabis indica causes more of a “body high”. Cannabis ruderalis, by contrast, is less well used due to its low Tetrahydrocannabinol levels.

What is Tetrahydrocannabinol?

Tetrahydrocannabinol (or THC) is one of the principle psychoactive components in Cannabis. It a chemical that is believed to be a plant defensive mechanism against herbivores. THC is a cannabinoid, a type of chemical that attaches to the cannabinoid receptors in the body, and it is this pathway that many scientists are exploring for future neuroprotective therapies for Parkinson’s disease (For a good review on the potential cannabinoid-based therapies for Parkinson’s disease, click here).

A second type of cannabinoid is Cannabidiol (or CBD). CBD is considered to have a wider scope for potential medical applications. This is largely due to clinical reports suggesting reduced side effects compared to THC, in particular a lack of psychoactivity.

So what research has been done regarding Cannabis and Parkinson’s disease?

In 2004, a group of scientists in Prague (Czech Republic) were curious to determine cannabis use in people with Parkinson’s disease, so they conducted a study and published their results:

Title: Survey on cannabis use in Parkinson’s disease: subjective improvement of motor symptoms.
Authors: Venderová K, Růzicka E, Vorísek V, Visnovský P.
Journal: Mov Disord. 2004 Sep;19(9):1102-6.
PMID: 15372606

The researchers posted out 630 questionnaires to people with Parkinson’s disease in Prague. In total, 339 (53.8%) completed questionnaires were returned to them. Of these, 85 people reported Cannabis use (25.1% of returned questionnaires). They usually consumed it with meals (43.5%), and most of them were taking it once a day (52.9%).

After consuming cannabis, 39 responders (45.9%) described mild or substantial alleviation of their Parkinson’s symptoms in general, 26 (30.6%) improvement of rest tremor, 38 (44.7%) alleviation of rigidity (bradykinesia), 32 (37.7%) alleviation of muscle rigidity, and 12 (14.1%) improvement of L-dopa-induced dyskinesias.

Importantly, half of the people who consumed cannabis experience no effect on their Parkinson’s disease features, and four responders (4.7%) reported that cannabis actually worsened their symptoms. So while this survey suggested some positive effects of cannabis in the treatment of Parkinson’s disease, it is apparent that the effect is different between people.

Additional surveys have been conducted around the world, with similar results (Click here to read more on this).

Have there been any clinical trials?

In the 1990s, there was a very small clinical study of cannabis use as a treatment option for Parkinson’s disease, and this study failed to demonstrate any positive outcome. In the study, none of the 5 people with Parkinson’s disease experienced any effect on their Parkinson’s motor features after a week of smoking cannabis (click here for more on this).

This study was followed up by a larger study:

Title: Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.
Authors: Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP.
Journal: Neurology. 2004 Oct 12;63(7):1245-50.
PMID: 15477546

In this randomized, double-blind, placebo-controlled study, 19 people with Parkinson’s disease randomly received either oral cannabis extract or a placebo (twice daily) for 4 weeks. They then took no treatment for an intervening 2-week ‘washout’ period, before they were given the opposite treatment for 4 weeks (so if they received the cannabis extract during the first 4 weeks, they would be given the placebo during the second 4 weeks). In all cases, the participants and the researchers were ‘blind’ to (unaware of) which treatment was being given.

The results indicated that cannabis was well tolerated by all of the participants in the study, but that it had no pro- or anti-Parkinsonian actions. The researchers found no evidence for a treatment effect on levodopa-induced dyskinesia.

In addition to this study, there has been a recent double-blind clinical study of cannabidiol (CBD, mentioned above) in the treatment of Parkinson’s disease:

Title: Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial.
Authors: Chagas MH, Zuardi AW, Tumas V, Pena-Pereira MA, Sobreira ET, Bergamaschi MM, dos Santos AC, Teixeira AL, Hallak JE, Crippa JA.
Journal: J Psychopharmacol. 2014 Nov;28(11):1088-98.
PMID: 25237116

The Brazilian researchers who conducted the study took 21 people with Parkinson’s disease and assigned them to one of three groups which were treated with placebo, small dose of CBD (75 mg/day) or high dose of CBD (300 mg/day). They found that there was no positive effects by administering CBD to people with Parkinson’s disease, except in their self-reported measures on ‘quality of life’.

So what does all of this mean?

Firstly, let us be clear that we are not trying to discredit Mr Frizell or suggest that what he is experiencing is not a real effect. The video he has uploaded suggests that he is experiencing very positive benefits by consuming cannabis to help treat his tremors.

Having said that, based on the studies we have reviewed above we (here at the SoPD) have to conclude that the clinical evidence supporting the idea of cannabis as a treatment for Parkinson’s disease is inconclusive. There does appear to be some individuals (like Mr Frizell) who may experience some positive outcomes by consuming the drug, but there are also individuals for whom cannabis has no effect.

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One of the reasons that cannabis may not be having an effect on everyone with Parkinson’s disease is that many people with Parkinson’s disease actually have a reduction in the cannabis receptors in the brain (click here for more on this). This reduction is believed to be due to the course of the disease. If there are less receptors for cannabis to bind to, there will be less effect of the drug.

Ok, but how might cannabis be having a positive effect on the guy in the video?

Cannabis is known to cause the release of dopamine in the brain – the chemical classically associated with Parkinson’s disease (Click here and here for more on this). Thus the positive effects that Mr Frizell is experiencing may simply be the result of more dopamine in his brain, similar to taking an L-dopa tablet. Whether enough dopamine is being released to explain the full effect is questionable, but this is still one possible explanation.

There could be questions regarding the long term benefits of Mr Frizell’s cannabis use, as long term users of cannabis generally have reduced levels of dopamine being released in the brain (Click here for more on this). Although the drug initially causes higher levels of dopamine to be released, over time (with long term use) the levels of dopamine in the brain gradually reduce.

I live in the UK. Is it legal for me to try using Cannabis for my Parkinson’s disease?

National status on Cannabis possession for medical purposes. Source: Wikipedia

The map above is incorrect, with regards to the UK at least (and may be incorrect for other regions as well).

According to the Home Office, it is illegal for UK residents to possess cannabis in any form (including medicinal).

Cannabis is illegal to possess, grow, distribute or sell in the UK without the appropriate licences. It is a Class B drug, which carries penalties for unlicensed dealing, unlicensed production and unlicensed trafficking of up to 14 years in prison (Source: Wikipedia; and if you don’t trust Wikipedia, here is the official UK Government website).

In 1999, a major House of Lords inquiry made the recommendation that cannabis should be made available with a doctor’s prescription. The government of the U.K., however, has not accepted the recommendations. Cannabis is not recognised as having any therapeutic value under the law in England and Wales.

Having said all of this, there has recently been an all-party group calls for the legalisation regarding cannabis for medicinal uses to be changed (click here for more on this). Whether this will happen is yet to be seen.

So the answer is “No, you are not allowed to use cannabis to treat your Parkinson’s disease”.

(And here is where things get a really grey)

There is a cannabis-based product – Sativex – which can be legally prescribed and supplied under special circumstances. Sativex is a mouth spray developed and manufactured by GW Pharmaceuticals in the UK. It is derived from two strains of cannabis leaf and flower, cultivated for their controlled proportions of the active compounds
THC and CBD.

In 2006, the Home Office licensed Sativex so that:

  • Doctors could privately prescribe it (at their own risk)
  • Pharmacists could possess and dispense it
  • Named patients with a prescription could possess

In June 2010 the Medicines Healthcare Regulatory products Agency (MHRA) authorised Sativex as an extra treatment for patients with spasticity due to Multiple Sclerosis (MS). Importantly, doctors can also prescribe it for other things outside of the authorisation, but (again) this is at their own risk.

EDITORIAL NOTE: Given that possessing cannabis is illegal and that more research into the medicinal benefits of cannabis for Parkinson’s disease is required, we here are the SoPD can not endorse the use of cannabis for treating Parkinson’s disease.

While we are deeply sympathetic to the needs of many individuals within the Parkinson’s community and agree with a reconsideration of the laws surrounding the medicinal use of cannabis, we are also aware of the negative consequences of cannabis use (which can differ from person to person).

If a person with Parkinson’s disease is considering a change in their treatment regime for any reason, we must insist that they first discuss the matter with their trained medical physician before undertaking any changes.

The information provided here is strictly for educational purposes only.

The banner for today’s post was sourced from the IBTimes.

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Published by Simon

I am the Deputy Director of Research at the Cure Parkinson’s Trust. Before that I was working as a Parkinson’s research scientist at the University of Cambridge where I conducted both clinical- and lab-based research on Parkinson’s. I have worked in the Parkinson’s research field for over 15 years – both academically and in biotech ventures. In addition, I am the president of my local Parkinson’s UK support branch in North Hertfordshire. All of my views/opinions expressed here are solely my own, and may not reflect the views of my employer or associated parties. View all posts by Simon

14 thoughts on “ Cannabis and Parkinson’s disease ”

There is vastly more research on cannabis for Parkinson’s than you suggest.

My apologies for the length of this comment but I hope it is helpful.

Cannabinoid–Dopamine Interaction in the Pathophysiology and Treatment of CNS
Disorders (full – 2010)
http://onlinelibrary.wiley.com/doi/10.1111/j.1755-5949.2010.00144.x/full
Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a
neuroprotective therapeutic modality. (full – 2010)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848893/?tool=pubmed
Loss of cannabinoid CB1 receptor expression in the 6-hydroxydopamine-induced
nigrostriatal terminal lesion model of Parkinson’s disease in the rat. (full – 2010)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659808/
Cannabinoids and Dementia: A Review of Clinical and Preclinical Data
(link to PDF – 2010) http://www.mdpi.com/1424-8247/3/8/2689
The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and
non-dyskinetic 6-hydroxydopamine lesioned rats. (abst – 2010)
http://www.ncbi.nlm.nih.gov/pubmed/20888328
In vivo type 1 cannabinoid receptor mapping in the 6-hydroxydopamine lesion rat model
of Parkinson’s disease. (abst – 2010) http://www.ncbi.nlm.nih.gov/pubmed/20026090
Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by
the proteasomal dysfunction. (full – 2011)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145842/?tool=pubmed
Is lipid signaling through cannabinoid 2 receptors part of a protective system?
(full – 2011) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062638/
Prospects for cannabinoid therapies in basal ganglia disorders. (full – 2011)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165947/
Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in
animal models of Parkinson’s disease (full – 2011)

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against
MPTP Neurotoxicity by Inhibiting Microglial Activation. (full – 2011)
http://www.jimmunol.org/content/187/12/6508.full?sid=c3422dd2-7ad0-42e4-a862-845dc670f7cf
Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for
membrane fluidity disturbance. (full – 2011)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165948/
Endocannabinoid hydrolysis generates brain prostaglandins that promote
neuroinflammation (full – 2011)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249428/
Therapeutic Potential of Cannabinoids in the Treatment of Neuroinflammation
Associated with Parkinson’s Disease (abst – 2011)
http://www.unboundmedicine.com/medline/ebm/record/21568925/abstract/Therapeutic_Potential_of_Cann
abinoids_in_the_Treatment_of_Neuroinflammation_Associated_with_Parkinson%27s_Disease_
Regional changes in type 1 cannabinoid receptor availability in Parkinson’s disease in
vivo (abst – 2011)
http://www.unboundmedicine.com/medline/ebm/record/21459482/abstract/Regional_changes_in_type_1_c
annabinoid_receptor_availability_in_Parkinson%27s_disease_in_vivo_
Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism:
preclinical Parkinson disease. (abst – 2011)
http://www.ncbi.nlm.nih.gov/pubmed/20862500
Homeostatic changes of the endocannabinoid system in Parkinson’s disease.
(abst – 2011)
http://www.unboundmedicine.com/medline/ebm/record/21412829/abstract/Homeostatic_changes_of_the_e
ndocannabinoid_system_in_Parkinson%27s_disease_
Increased vulnerability to 6-hydroxydopamine lesion and reduced development of
dyskinesias in mice lacking CB1 cannabinoid receptors (abst – 2011)
http://europepmc.org/abstract/med/19419794
The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcription
(full – 2012) http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.02175.x/full
The Therapeutic Potential of Cannabis and Cannabinoids (full – 2012)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442177/
Cannabinoid modulation of neuroinflammatory disorders. (full – 2012)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/
Review article: The endocannabinoid system in normal and pathological brain ageing
(full – 2012)
http://rstb.royalsocietypublishing.org/content/367/1607/3326.full?sid=161e7b36-5055-448b-962e-
697c782e901d
The cannabinoid agonist WIN55212-2 decreases l-DOPA-induced PKA activation and
dyskinetic behavior in 6-OHDA-treated rats. (full – 2012)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273613/
Cannabinoids and value-based decision making: implications for neurodegenerative
disorders. (full – 2012) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496267/
The decrease of dopamine D(2)/D(3) receptor densities in the putamen and nucleus
caudatus goes parallel with maintained levels of CB(1) cannabinoid receptors in
Parkinson’s disease: A preliminary autoradiographic study with the selective dopamine
D(2)/D(3) antagonist [(3)H]raclopride and the novel CB(1) inverse agonist
[(125)I]SD7015. (full – 2012) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180092/
Targeting the endocannabinoid system with cannabinoid receptor agonists:
pharmacological strategies and therapeutic possibilities (full – 2012)
http://rstb.royalsocietypublishing.org/content/367/1607/3353.full?sid=1569c370-cd5c-4358-89ff-
857201f5e069
Δ(9) -THC exerts a direct neuroprotective effect in a human cell culture model of
Parkinson’s disease. (abst – 2012) http://www.ncbi.nlm.nih.gov/pubmed/22236282
Contribution of genetic variants to pain susceptibility in Parkinson disease.
(abst – 2012) http://www.ncbi.nlm.nih.gov/pubmed/22473870
Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity of
parkinsonian rats induced by reserpine. (full – 2013)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730975/
Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency
Stimulation in Parkinsonian Rat. (full – 2013)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617149/
Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible
structure-specific plasticity process in 6-OHDA lesioned rats. (full – 2013)
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076874
The Influence of Cannabinoids on Generic Traits of Neurodegeneration. (full – 2013)
http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full
Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-
HT1A receptors activation in mice. (full – 2013)
http://www.sciencedirect.com/science/article/pii/S0278584613001164
A spontaneous deletion of α-Synuclein is associated with an increase in CB1 mRNA
transcript and receptor expression in the hippocampus and amygdala: Effects on alcohol
consumption (full – 2013) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931467/
Natural Cannabinoids Improve Dopamine Neurotransmission and Tau and Amyloid
Pathology in a Mouse Model of Tauopathy. (link to PDF – 2013)
http://content.iospress.com/articles/journal-of-alzheimers-disease/jad130050
Therapeutic Potential of Cannabinoids in Neurodegenerative Disorders: A Selective
Review. (abst – 2013) http://www.ncbi.nlm.nih.gov/pubmed/23829360
Δ9-Tetrahydrocannabinol is protective through PPARγ dependent mitochondrial
biogenesis in a cell culture model of Parkinson’s Disease
(abst – 2013) http://jnnp.bmj.com/content/84/11/e2.58.abstract
Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a
mouse model of Parkinson´s disease. (abst – 2013)
http://www.ncbi.nlm.nih.gov/pubmed/24140894
The combination of oral L-DOPA/rimonabant for effective dyskinesia treatment and
cytological preservation in a rat model of Parkinson’s disease and L-DOPA-induced
dyskinesia. (abst – 2013) http://www.ncbi.nlm.nih.gov/pubmed/24196024
L-DOPA-treatment in primates disrupts the expression of A(2A) adenosine-CB(1)
cannabinoid-D(2) dopamine receptor heteromers in the caudate nucleus.
(abst – 2013) http://www.sciencedirect.com/science/article/pii/S0028390813005121
The endocannabinoid system: a putative role in neurodegenerative diseases.
(full – 2014) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070159/
The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and
ERK1/2 phosphorylation in 6-OHDA-lesioned rats. (full – 2014)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226453/
Endocannabinoid signalling and the deteriorating brain. (full – 2014)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471876/
Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases
(full – 2014) http://www.mdpi.com/1420-3049/19/11/18781/htm
Activation of PPAR gamma receptors reduces levodopa-induced dyskinesias in 6-OHDAlesioned
rats. (full – 2014) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323744/
Medical Cannabis Research, What the Science Says (article – 2014)
http://www.safeaccessnow.org/medical_cannabis_research_what_does_the_evidence_say
L-DOPA disrupts adenosine A2A-cannabinoid CB1-dopamine D2 receptor heteromer
cross-talk in the striatum of hemiparkinsonian rats: Biochemical and behavioral studies.
(abst – 2014) http://www.sciencedirect.com/science/article/pii/S0014488614000028
Cannabidiol Normalizes Capase 3, Synatophsin, and Mitochondrial Fission Protein
DNM1L Expression Levels in Rats with Brain Iron Overload: Implications for
Neuroprotection (abst – 2014) http://www.ncbi.nlm.nih.gov/pubmed/23893294
Genome-wide microarray analysis identifies a potential role for striatal retrograde
endocannabinoid signaling in the pathogenesis of experimental l-DOPA-induced
dyskinesia (abst – 2014) http://www.ncbi.nlm.nih.gov/pubmed/24599755
Cannabis (Medical Marijuana) Treatment for Motor and Non-Motor Symptoms of
Parkinson Disease: An Open-Label Observational Study. (abst – 2014)
http://www.ncbi.nlm.nih.gov/pubmed/24614667
Cannabidiol can improve complex sleep-related behaviours associated with rapid eye
movement sleep behaviour disorder in Parkinson’s disease patients: a case series.
(abst – 2014) http://www.ncbi.nlm.nih.gov/pubmed/24845114
The monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell
phenotype in the chronic MPTP mouse model. (abst – 2014)
http://www.neurobiologyofaging.org/article/S0197-4580(14)00384-4/abstract
Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An
exploratory double-blind trial. (abst – 2014)
http://www.ncbi.nlm.nih.gov/pubmed/25237116
Identification of CB2 receptors in human nigral neurons that degenerate in Parkinson’s
disease. (abst – 2014)
http://www.sciencedirect.com/science/article/pii/S0304394014009318
Self-Reported Efficacy of Cannabis and Other Complementary Medicine Modalities by
Parkinson’s Disease Patients in Colorado (full – 2015)
http://www.hindawi.com/journals/ecam/2015/874849/
Promising cannabinoid-based therapies for Parkinson’s disease: motor symptoms to
neuroprotection. (full – 2015)

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Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons
Orchestrates Motor Control (full – 2015)
http://www.cell.com/cell-reports/fulltext/S2211-1247%2815%2901163-8
Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease.
(full – 2015) http://www.sciencedirect.com/science/article/pii/S0014488615300583
The therapeutic potential of cannabinoids for movement disorders. (full – 2015)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357541/
Endocannabinoid Signaling in Motivation, Reward, and Addiction: Influences on
Mesocorticolimbic Dopamine Function. (full – 2015)
http://www.sciencedirect.com/science/article/pii/S007477421500135X
Cannabinoid-dopamine interactions in the physiology and physiopathology of the basal
ganglia. (full – 2015) http://onlinelibrary.wiley.com/doi/10.1111/bph.13215/full
Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?
(full – 2015) http://link.springer.com/article/10.1007%2Fs13311-015-0367-5
Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in
macaques: changes following experimental parkinsonism (link to PDF – 2015)
http://link.springer.com/article/10.1007/s00429-014-0823-8
Potential of the cannabinoid CB2 receptor as a pharmacological target against
inflammation in Parkinson’s disease. (abst – 2015)
http://www.sciencedirect.com/science/article/pii/S0278584615000664
The role of cannabinoids and leptin in neurological diseases. (abst – 2015)
http://www.ncbi.nlm.nih.gov/pubmed/25880465
Differential upregulation of the cannabinoid CB2 receptor in neurotoxic and
inflammation-driven rat models of Parkinson’s disease. (abst – 2015)
http://www.sciencedirect.com/science/article/pii/S0014488615001211
Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB 2
Receptors. (abst – 2015) http://www.ncbi.nlm.nih.gov/pubmed/25976369
N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of
Resolution. (abst – 2015) http://www.ncbi.nlm.nih.gov/pubmed/26055231
Cannabinoids for the Treatment of Movement Disorders. (abst – 2015)
http://www.ncbi.nlm.nih.gov/pubmed/26206230
Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From
Preclinical Models to Clinical Applications. (abst – 2015)
http://www.ncbi.nlm.nih.gov/pubmed/26260390
Endocannabinoids and Neurodegenerative Disorders: Parkinson’s Disease, Huntington’s
Chorea, Alzheimer’s Disease, and Others. (abst – 2015)
http://www.ncbi.nlm.nih.gov/pubmed/26408163
Dopamine-dependent CB1 receptor dysfunction at corticostriatal synapses in
homozygous PINK1 knockout mice. (abst – 2015)
http://www.sciencedirect.com/science/article/pii/S0028390815301441
The neuroprotection of cannabidiol against MPP+-induced toxicity in PC12 cells
involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and
might be relevant to Parkinson’s disease (abst – 2015)
http://www.sciencedirect.com/science/article/pii/S0887233315300047
THC exerts neuroprotective effect in glutamate affected murine primary mesencephalic
cultures and neuroblastoma N18TG2 cells (abst – 2015)
https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1565754
Modulation of cellular redox homeostasis by the endocannabinoid system.
(full – 2016) http://rsob.royalsocietypublishing.org/content/6/4/150276
Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by
restoring proteins involved in mitochondrial biogenesis. (full – 2016)
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path
%5B%5D=10314&path%5B%5D=32486
Targeting the cannabinoid CB2 receptor to attenuate the progression of motor deficits in
LRRK2-transgenic mice. (abst – 2016)
http://www.sciencedirect.com/science/article/pii/S1043661816302663
Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-
hydroxydopamine lesioned rat brains. (abst – 2016)
http://www.ncbi.nlm.nih.gov/pubmed/27155397
Upregulation of the cannabinoid CB2 receptor in environmental and viral inflammationdriven
rat models of Parkinson’s disease. (abst – 2016)
http://www.sciencedirect.com/science/article/pii/S0014488616301790
Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinsons disease.
(abst – 2016) http://www.ncbi.nlm.nih.gov/pubmed/27318096
Endocannabionoid System in Neurological Disorders. (abst – 2016)
http://www.ncbi.nlm.nih.gov/pubmed/27364363
The bright side of psychoactive substances: cannabinoid-based drugs in motor diseases.
(abst – 2016) http://www.ncbi.nlm.nih.gov/pubmed/27373318
Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia
in mice: Possible mechanism of action (abst – 2016)
https://www.researchgate.net/publication/304669756_Coadministration_of_cannabidiol_and_capsazepine_
reduces_L-DOPA-induced_dyskinesia_in_mice_Possible_mechanism_of_action
Type-2 cannabinoid receptors in neurodegeneration. (abst – 2016)
http://www.sciencedirect.com/science/article/pii/S1043661816306983
Cannabinoid Type 2 (CB2) Receptors Activation Protects against Oxidative Stress and
Neuroinflammation Associated Dopaminergic Neurodegeneration in Rotenone Model of
Parkinson’s Disease. (abst – 2016) http://www.ncbi.nlm.nih.gov/pubmed/27531971
CB2 receptor activation prevents glial-derived neurotoxic mediator production, BBB
leakage and peripheral immune cell infiltration and rescues dopamine neurons in the
MPTP model of Parkinson’s disease. (abst – 2016)
http://www.ncbi.nlm.nih.gov/pubmed/27534533

Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a
reduction in movement in an animal model of Parkinson’s disease (abst – 2000)
http://www.ncbi.nlm.nih.gov/pubmed/10877836
Control of the cell survival/death decision by cannabinoids. (abst – 2001)
http://www.ncbi.nlm.nih.gov/pubmed/11269508
Experimental parkinsonism alters endocannabinoid degradation: implications for striatal
glutamatergic transmission. (full – 2002) http://www.jneurosci.org/content/22/16/6900.long
US Patent 6630507 – Cannabinoids as antioxidants and neuroprotectants (full – 2003)
(Assignee (owner)- the US GOVERNMENT!)
http://www.google.com/patents/US6630507
Future of Cannabis and Cannabinoids in Therapeutics (link to PDF – 2003)
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.597.1387&rank=7
Therapeutic potential of cannabinoids in CNS disease. (abst – 2003)
http://www.ncbi.nlm.nih.gov/pubmed/12617697
Cannabis trial on Parkinson’s (news – 2003)
http://news.bbc.co.uk/2/hi/uk_news/england/devon/2956273.stm
Survey on cannabis use in Parkinson’s disease: subjective improvement of motor
symptoms. (abst – 2004)
http://www.cannabis-med.org/studies/ww_en_db_study_show.php?s_id=33
Marijuana Compounds May Aid Parkinson’s Disease (news – 2004)
http://cannabisnews.com/news/19/thread19725.shtml
Depression in Parkinson’s disease is related to a genetic polymorphism of the
cannabinoid receptor gene (CNR1) (full – 2005)
http://www.nature.com/tpj/journal/v5/n2/full/6500301a.html
Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in
vitro: relevance to Parkinson’s disease. (abst – 2005)
http://www.ncbi.nlm.nih.gov/pubmed/15837565?dopt=Abstract
Cannabinoid control of motor function at the basal ganglia. (abst – 2005)
http://www.ncbi.nlm.nih.gov/pubmed/16596785
Cannabinoids In Medicine: A Review Of Their Therapeutic Potential (full – 2006)

Anti-dyskinetic effects of cannabinoids in a rat model of Parkinson’s disease: role of CB1
and TRPV1 receptors (full – 2007) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2128772/?
tool=pmcentrez
The endocannabinoid system in targeting inflammatory neurodegenerative diseases
(full – forum repost – 2007)
http://www.420magazine.com/forums/als-amyotrophic-lateral-sclerosis/149304-endocannabinoid-systemtargeting-inflammatory-neurodegenerative-diseases.html
Clinical research Cannabinoids in health and disease (link to PDF – 2007)
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.288.5352&rank=23
Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson’s
disease: importance of antioxidant and cannabinoid receptor-independent properties.
(abst – 2007) http://www.ncbi.nlm.nih.gov/pubmed/17196181
Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s
disease models. (abst – 2007) http://www.ncbi.nlm.nih.gov/pubmed/17287809
Cannabinoids and neuroprotection in motor-related disorders. (abst – 2007)
http://www.ncbi.nlm.nih.gov/pubmed/18220777
Comparison Analysis of Gene Expression Patterns between Sporadic Alzheimer’s and
Parkinson’s Disease (abst – 2007) http://www.ncbi.nlm.nih.gov/pubmed/18198416
Marijuana-Like Chemicals Helps Treat Parkinson’s (news – 2007)
http://cannabisnews.com/news/22/thread22608.shtml
Parkinsons’ Helped By Marijuana-Like Chemicals In Brain (news – 2007)
http://www.medicalnewstoday.com/releases/62616.php
Enhancing Activity Of Marijuana-Like Chemicals In Brain Helps Treat Parkinson’s
Symptoms In Mice (news – 2007)
http://www.sciencedaily.com/releases/2007/02/070207171915.htm
The importance of the endocannabinoid-system (news – 2007)
http://www.news-medical.net/news/2007/10/15/31174.aspx
Paraquat induces apoptosis in human lymphocytes: protective and rescue effects of
glucose, cannabinoids and insulin-like growth factor-1. (abst – 2008)
http://www.ncbi.nlm.nih.gov/pubmed/18365879
The cannabinoid CP55,940 prolongs survival and improves locomotor activity in
Drosophila melanogaster against paraquat: implications in Parkinson’s disease.
(abst – 2008) http://www.ncbi.nlm.nih.gov/pubmed/18538428
LSUHSC research reports new method to protect brain cells from diseases like
Alzheimer’s (news – 2008) http://www.eurekalert.org/pub_releases/2008-08/lsuh-lrr082008.php
WIN55,212-2, a Cannabinoid Receptor Agonist, Protects Against Nigrostriatal Cell Loss
in the MPTP Mouse Model of Parkinson’s Disease (full – 2009)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755595/?tool=pubmed
Cannabidiol: a promising drug for neurodegenerative disorders? (full – 2009)
http://onlinelibrary.wiley.com/doi/10.1111/j.1755-5949.2008.00065.x/full
The endocannabinoid system as a target for the treatment of motor dysfunction.
(full – 2009) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697699/
Cannabidiol for the treatment of psychosis in Parkinson’s disease (abst – 2009)
http://jop.sagepub.com/cgi/content/abstract/23/8/979?
maxtoshow=&hits=80&RESULTFORMAT=&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1920&re
sourcetype=HWCIT
Medical Marijuana and Parkinson’s Disease (news/ad – 2009)
https://www.marijuanadoctors.com/content/ailments/view/158?ailment=parkinson-s-disease

Hi Peter, thanks for the messages (and all of the links!) and yes, we completely agree: there has been mountains of work in this area. There does appear to be major future potential for derivatives of Cannabinoids in neurodegenerative conditions (not just PD).

In our post, however, we were primarily focusing on the clinical side of things. The bulk of the links you have kindly provided deal mostly with preclinical experiments (on cells in culture or animal models of PD). While we certainly hope that novel future therapies will result from those efforts, in the post we were simply providing a short review of what has been tested on subjects in the clinic. And as we say, the published results appear to be mixed with some people having positive benefits while other experience limited effects.

Thanks very much for contributing! Much appreciated.

Yep, there’s a terrible lack of clinical work on all aspects of medicinal cannabis and cannabinoids, mainly because of its schedule 1 status. That is beginning to change and there are clinical trials going on in Israel, Canada and California. Probably the most promising area for PD is cannabidiol (CBD) which is non-psychoactive, completely safe on all available evidence and easily available in the UK.

Hi there, great write up. I do have to correct your information on Sativex which is, in fact, a full plant extract. Extracts from different strains (High THC/Low CBD Eg: Skunk and High CBD/low THC Eg: Charlottes Web are mixed to produce a 1-1 Balanced THC/CBD ratio. The final product contains all cannabinoids and terpenes etc from the whole plant, plus a bit of alcohol to make it a tincture and peppermint for taste! Then they price it so high, our own NHS cant afford it so any patients who have been able to get it, pay about £8000 per year. The vast majority of our patients (at United Patients Alliance) find it is not strong enough to mange pain properly so have replaced it with herbal cannabis, cheaper and more effectively.

Opps. Thanks for pointing out the error Jon. And for highlighting some of the issues faced by affected folks that we didn’t cover in the post. Much appreciated.