Cannabis and Parkinson’s disease

medimarijuana

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).


medicinal

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.

But first:

What exactly is Cannabis?

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?

thc-structure

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:

survey

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?

Yes, there have.

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:

cannabistitle

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:

cbd

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.

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?

legality_of_cannabis_for_medical_purposes_new

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”.

Except…

(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.

Advertisements

8 comments

  1. Peter Reynolds

    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)
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165958/pdf/bph0163-1495.pdf
    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)
    http://www.molecularneurodegeneration.com/content/pdf/s13024-015-0012-0.pdf
    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

    Like

  2. Peter Reynolds

    And more:

    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)
    http://www.doctordeluca.com/Library/WOD/WPS3-MedMj/CannabinoidsMedMetaAnalysis06.pdf
    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

    Liked by 1 person

  3. Simon

    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.

    Like

    • Peter Reynolds

      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.

      Like

  4. jliebling

    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.

    Like

    • Simon

      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.

      Like

  5. Simon

    We have had a series of attempts to post a link (to a Chilean website) based on the topic of this post today. For some reason the comment does not want to appear on the page (I’m not sure why – but thanks to the contributor), so I’m providing the comment and link here:
    “No obstante, hay que tener muy en cuenta que los efectos de los cannabinoides no son iguales en todos los pacientes. A veces, sencillamente, no hacen efecto. Es muy importante tenerlo en….”
    (Google Translation: However, we must bear in mind that the effects of cannabinoids are not equal in all patients. Sometimes simply do not take effect. It is very important to keep in…)
    Link: http://titularesdechile.cl/derivados-del-cannabis-investigando-nuevas-herramientas-contra-el-parkinson/

    Like

  6. Pingback: Improving the SoPD blog 2017 – any thoughts/suggestions? | The Science of Parkinson's disease

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s