Cannabis and Parkinson’s disease
Parkinson's Since the 1970s, the scientific community - prompted by frequent reports from patients opting for self-medication - has been able to focus its research on cannabinoids for the treatment of Parkinson’s disease. The number of studies conducted on the subject continues to be relatively low, despite recent renewed efforts in this direction owing to the frequency of cases reported by patients suffering from the disease.
Dementia is a loss or severe deterioration of cognitive capacity, which can either be temporary, or represent a long-term psychological decline. There are a number of diseases that are considered a form of dementia, among the most common of which is Parkinson’s disease.
One of the main symptoms of Parkinson’s disease is a deterioration of motor functions, which can be grouped into four different categories: tremor, rigidity, slowness of movement and postural instability. Tremors are certainly the most visible and well-known of the motor symptoms, but there are numerous other specific motor symptoms that patients can suffer from, depending on the individual.
In addition to the motor symptoms, there are also neuropsychiatric symptoms of Parkinson’s disease that can include a deterioration of certain cognitive functions, mood disorders or behavioural disorders. These disorders largely manifest themselves as problems with concentration, memory, language and visuospatial skills. The progressive deterioration of this cognitive capacity can, over the long-term, result in a much more severe manifestation of dementia.
Since the 1970s, the scientific community – prompted by frequent reports from patients opting for self-medication – has been able to focus its research on cannabinoids for the treatment of Parkinson’s disease. The number of studies conducted on the subject continues to be relatively low, despite recent renewed efforts in this direction owing to the frequency of cases reported by patients suffering from the disease.
One of the physiopathological characteristics of Parkinson’s disease is the malfunctioning of the dopaminergic system, whereby certain brain structures suffer from a deficiency of dopamine as well as several other neurotransmitters, leading to the cell degeneration which is at the root of cognitive function impairment.
In 2004, tests of synthetic cannabinoids on rats provided unequivocal proof that treatment based on cannabinoids could be the key to effective treatment of this disease.
In the first instance, the rats were injected with a laboratory drug that played the role of a THC (one of the major psychoactive substances in marijuana) agonist, then with a toxin that provoked the same effects as those of Parkinson’s disease. The researchers discovered that it was almost impossible to distinguish the brains of the infected rats from the brains of the healthy rats.
Secondly, a group of different rats was injected with the toxin, then with the agonist, to confirm that cannabis also has neuroprotective properties. Here again, the results were positive when THC and cannabidiol were injected (THC alone giving similarly positive results but to a lesser degree), slowing down the progression of the disease for a period equivalent to several years in human terms.
The discovery of pain as a symptom of Parkinson’s disease is relatively recent. Even though pain exists in 50% to 80% of patients, it had not previously been linked to the disease in any conclusive way. However, this pain is often severe to the point of surpassing the other symptoms in terms of severity, and it can have psychological repercussions in the long term such as depression and anxiety.
Pain can be a direct consequence of the motor disorders, such as pain suffered as a result of prolonged muscle rigidity, or even pain linked to dystonia, postural problems, and more rarely, coming directly from the cervical region.
The study was able to examine eight different genes known to be involved with pain in general in a group of 237 Parkinson’s disease sufferers. The researchers then discovered that these genes reacted to pain in a recognisable way, i.e. by demonstrating characteristics typically linked to the endocannabinoid system and to the consumption of substances such as marijuana.
The laboratory was able to conclude that the pain experienced as part of the disease could be calmed by consuming marijuana; the researchers have however recommended continued research in order to optimise potential treatment based on the individual characteristics of the patients’ gene mapping.
Dystonia and dyskinesia
Research focused on cannabinoids has already proven – for numerous illnesses – that these have an impact on a wide range of motor symptoms manifested by tremors, spasms or by muscle rigidity; this is in fact one of the properties of the mouth sprays based on cannabis concentrate such as Sativex, currently used in patients with multiple sclerosis.
In Parkinson’s, certain treatments intended to relieve these symptoms can themselves lead to additional movement disorders on top of the already severe motor symptoms caused by the illness. These disorders often being considered the most debilitating characteristics of this disease, it is hardly surprising that the main body of research is focused on these.
A study that started in 1985 was already based on tests carried out on a patient who had suffered from Parkinsonism for many years, showing dystonia in all limbs as well as L-Dopa-induced dyskinesia, i.e. dyskinesia provoked by long-term treatment with one of the most effective remedies used in Parkinson’s disease and Parkinsonism: L-Dopa.
Varying dosages of pharmaceutical drugs commonly used to combat the symptoms of Parkinson’s disease – including dyskinesia – have shown results that, while positive, were only marginal. However, tests that included varying dosages of cannabidiol, one of the cannabinoids most researched for its medicinal benefits, have shown more than significant results. A dose of between 100 mg/day and 200 mg/day of cannabidiol was able to reduce the clinical fluctuations normally experienced and alleviate dyskinesia by up to 30%.
No further improvement was observed for greater doses, while side effects did appear such as vertigo, drowsiness and an increase in the severity of the symptoms of Parkinson’s.
Putting a stop to the administration of cannabidiol caused severe generalized dystonia and increased sensitivity to previously ineffective treatments.
In 1986, a similar study carried out on patients suffering from dystonia confirmed these results, with an improvement in dystonia of between 20% and 50% as reported by the patients.
In 1998, research confirmed that the concentration of cannabinoid receptors in the globus pallidus could explain the impact of synthetic THC on dystonia and dyskinesia as this brain structure controls the regulation of voluntary movements.
In addition to these advances in terms of the proven efficacy of cannabis to combat the symptoms of Parkinson’s, there are regular discoveries linked to the endocannabinoid system and its functions that continue to enrich the limited knowledge on the pathology and physiopathology of this disease that is currently employed by modern medicine.
In 2007, a team of researchers from Stanford university thus made an important discovery relating to a brain structure called striatum, known for its activity relating to dopamine levels. Two types of cells found in this structure were distinguished for the first time, the first being responsible for initiating movement and the second for inhibiting involuntary movements. It transpires that a low dopamine level – one of the bases of the physiology of Parkinson’s disease – has a direct impact on the type of cells responsible for inhibiting movement, making them hyperactive, which would explain the difficulties with initiating a voluntary movement in sufferers.
Several tests were carried out to address this hyperactivity. The combination of a drug emulating dopamine and a drug intended to slow down the deterioration of the endocannabinoid system by concentrating on the enzymes responsible has shown impressive results, opening many avenues for future research on palliative treatment as well as on a cure.
Dosage and recent advances in research
Since the start of the 21st century, researchers have focused on one of the principal parameters preventing the development of a treatment based on cannabinoids validated by the medical community: dosage (see: Dystonia and dyskinesia, end of the 2nd paragraph).
In fact, although numerous patients disregard these recommendations for reasons that are fairly self-evident, the doctors most au fait with the research do not necessarily recommend self-medication. The risk faced in the case of overdose is an increase in the severity of the symptoms, which is of some significance – especially if we consider the complex and variable pharmacology of cannabinoids in all their forms.
This is why a certain number of observational studies have emerged in the last few months based on reports from hundreds of patients who have turned to cannabis for day-to-day relief.
In June 2013, an Australian laboratory published a study using the UPDRS (Unified Parkinson’s Disease Rating Scale), which measures the severity of the symptoms of the disease. The laboratory compared levels on this scale, in particular relating to the four cardinal signs of the motor symptoms of Parkinson’s disease, before and after taking cannabis. It was thus uncovered that the cannabinoids contained in the plant (or phytocannabinoids) had an impact not only on the tremors suffered but also on the muscle rigidity and akinesia (scarcity and slowness of bodily movement).
Tests were carried out on patients with an average age of 66 and were conducted before consuming cannabis, then 30 minutes after consuming cannabis. The differences in the scores obtained on each of the key motor symptoms were conclusive, especially insofar as these patients had been diagnosed on average 7.5 years previously.
The patients tested had a common variable: they were all regular consumers of cannabis, having opted of their own accord for self-medication. According to these patients, one “dose” of cannabis, i.e. one cannabis cigarette or one dose of vaporised cannabis, could provide relief for 2 to 3 hours.
Finally, an observational study presented by Israeli neuroscientists in March 2014 proved for the first time the efficacy of cannabinoids on a group of symptoms of Parkinson’s disease, including both motor and non-motor disorders. These findings represent incredible progress as these types of tests have always been difficult, or near impossible, because of the limited availability of medicinal cannabis for use in research.
According to the scientists concerned, the thorough nature of this study could be a catalyst for initiating the development of treatments based on cannabinoids; a treatment that could soon become a reality for the 7 million patients all over the world who suffer from Parkinson’s disease.
Marijuana-Like Compounds May Aid Array Of Debilitating Conditions Ranging From Parkinson’s Disease To Pain – October 27, 2004 – Society For Neuroscience – http://www.sciencedaily.com/releases/2004/10/041027102621.htm
Contribution of genetic variants to pain susceptibility in Parkinson disease – April 4, 2012 – European Journal of Pain – http://onlinelibrary.wiley.com/doi/10.1002/j.1532-2149.2012.00134.x/abstract
Beneficial and adverse effects of cannabidiol in a Parkinson patient with sinemet-induced dystonic dyskinesia – Neurology 1985- http://www.cannabis-med.org/studies/ww_en_db_study_show.php?s_id=142
Open label evaluation of cannabidiol in dystonic movement disorders – International Journal of Neuroscience 1986 – http://www.ncbi.nlm.nih.gov/pubmed/3793381
The effects of the cannabinoid receptor agonist nabilone on L-DOPA induced dyskinesia in patients with idiopathic Parkinson’s disease (PD) – Movement Disorders 1998 – http://www.cannabis-med.org/studies/ww_en_db_study_show.php?s_id=153
Enhancing activity of marijuana-like chemicals in brain helps treat Parkinson’s symptoms in mice – Stanford Medicine – http://med.stanford.edu/news_releases/2007/february/malenka.html
Medical Marijuana (Cannabis) Treatment For Motor And Non-Motor Symptoms In Parkinson’s Disease. An Open-Label Observational Study – MDS 17th International Congress of Parkinson’s Disease and Movement Disorders, Volume 28, June 2013 – http://www.mdsabstracts.com/abstract.asp?MeetingID=798&id=106491