Parkinson’s Disease and Medical Cannabis: An Overview
Spoiler alert: Medical cannabis will not cure Parkinson’s by itself, at least not with what we know now. But there are a number of ways it can be helpful – both now and in the future as we learn more. I am writing this to bring two audiences – the Parkinson’s and cannabis communities, each of whom may know little about the other – closer together.
In order to understand how cannabis may help, we need to look more closely at Parkinson’s Disease.
What Is Parkinson’s Disease?
Parkinson’s disease (PD) is a progressive neurodegenerative disease in which the neurons in a specific area of the brain (substancia nigra) are destroyed and no longer produce enough dopamine to allow certain neurotransmitters to send the necessary and appropriate signals through nerves to muscles in the body so that they can perform their functions correctly. Other chemicals in addition to dopamine, such as serotonin and norepinephrine (also known as noradrenaline), are also affected.
Why this happens is still unknown. For at least some people, there may be a genetic pre-disposition and several genes have already been identified. There is probably also a trigger, perhaps environmental, that sets off the death of the dopamine-producing neurons. Some potential triggers, including pesticides, have been identified. This process may even be an ongoing natural occurrence where whatever causes the death of the dopamine-producing cells occurs naturally in most of us but the damage is then repaired or prevented by something else in our body (until old age catches up or genes or environmental toxins interfere). This may occur much as cancer cells are often created in our bodies but then are destroyed by our immune system before we are aware of them.
Scientists are working hard to understand how all this works and although there are theories, there is still no definitive answer that would point to a ‘cure’. Some are looking to find what may be a ‘magic bullet’ that would destroy whatever is destroying the dopamine-producing cells and stop the degenerative process while others are looking to see if there is something that may better protect the dopamine-producing cells in the brain from being destroyed in the first place. Many scientists are now focusing on a protein called alpha-synuclein that seems to form clumps or ‘tangles’ known as Lewy bodies in people with PD.
Ultimately we hope scientists will find the cause and cure for the disease – but since they do not currently know how to stop the disease, physicians focus on alleviating symptoms.
Parkinson’s Disease Symptoms
The primary motor symptoms (involving movement) of Parkinson’s are tremor, slowness of movement (bradykinesia), rigidity or stiffness, gait problems, and postural instability. There seem to be two main types of Parkinson’s, with some people exhibiting primarily tremor and others having primarily gait problems, postural instability, and rigidity. All people with PD tend to have some slowness of movement, which involves not only movement of limbs but other muscles that also slow down, including those in the lungs, stomach, and colon (although physicians often classify those as ‘non-motor’ symptoms). The functioning of the brain can also slow down.
Parkinson’s can also cause bothersome non-motor symptoms, including depression, apathy or lack of motivation, anxiety, cognitive changes including slow thinking and memory problems, pain, insomnia, weight loss, fatigue, excessive daytime sleepiness, REM sleep disorder (acting out dreams), restless leg syndrome, soft voice, lack of facial expression, small handwriting, nausea, and hallucinations. Many of these are due to the effects of the loss of dopamine but a few can also be due to various Parkinson’s medications and some, such as depression, anxiety, or various pains may have existed independently of the Parkinson’s disease although PD may increase them.
Traditional Parkinson’s Disease Treatment
Since Parkinson’s is basically a disease of insufficient dopamine in the brain, the obvious fix is to supplement the dopamine. This is a little tricky since the dopamine molecule itself can’t cross the blood-brain barrier — but its precursor, levodopa, can. Since the 1970s, the primary medication for motor symptoms of Parkinson’s has been a combination of levodopa and carbidopa (carbidopa/levodopa; brand name is Sinemet). The carbidopa blocks the effect of levodopa on other parts of the body before it reaches the brain (thus making more available to the brain and also countering the vomiting that levodopa can cause). In the brain, levodopa is converted to dopamine. Most people with PD (except in very early stages) take carbidopa/ levodopa and it is usually quite effective in controlling PD symptoms, especially in early and mid years.
As time goes on, it may be more difficult to control the PD symptoms without also causing a side-effect called dyskinesias, or involuntary movements, usually of the limbs or upper body. These may be caused by over-medication with levodopa at any given time, long-term use of levodopa, fluctuating levels of levodopa in the body as it is taken in pills at specific times, or simply progression of the disease (physicians still debate this). Sometimes PD patients also experience strong muscle cramps called dystonias.
There are other medications that are sometimes or often used in the early stages of PD or to supplement carbidopa/levodopa later. These generally focus on extending, preserving, or mimicking the existing dopamine but they are less effective than levodopa. These medications include 1) dopamine agonists (ropinerole/Requip, pramipexole/Mirapex, rotigotine/Neupro) which are not dopamine but mimic it and bind to dopamine receptors, 2) MAO-B inhibitors (Selegeline/Eldepryl, Rasagiline/Azilect) which block an enzyme that breaks down dopamine, 3) anti-cholinergics (trihexyphenidyl/Artane and benztropine/Cogentin) which block brain receptors for acetycholine that balances out with dopamine, and 4) amantadine /Symmetrel.
Many of the ‘non-motor’ symptoms are helped by levodopa, but for others traditional physicians generally recommend a variety of other standard medications that may help those symptoms regardless of their cause.
Cannabis As A Potential Treatment Option
Cannabis sativa, the Latin name for marijuana, has been used for centuries around the world as a medicinal herb for a variety of ailments. Cannabis fibers, known as hemp, were also used for rope, clothing, and paper. It is only since a huge anti-marijuana campaign in the United States in the early 20th century that the herb has become taboo and banished from use.
With all this history, it is only in the last few decades that scientists have discovered the endocannabinoid system in our bodies – with cannabinoid receptors, many clustered in the brain but also others in nerves and the immune system throughout the body. Our bodies produce natural cannabinoids, such as anandamide and 2-arachidonoyl glycerol (2AG). Cannabinoids in marijuana also bind to these receptors. Knowledge of this system, how it works, and what it does is still a fairly new but growing field of scientific investigation.
Scientific progress also now allows us a much more sophisticated look at cannabis itself. Cannabis is actually composed of hundreds of chemicals – cannabinoids, which are unique to cannabis, and also terpenoids and flavonoids. When marijuana was most commonly sought for recreational use, cannabis was bred to promote the cannabinoid THC (delta-9-tetrahydrocannabinol), a molecule that is responsible for marijuana’s psychoactive ‘high’. In recent years, much attention has focused on the useful properties of another cannabinoid, CBD or cannabidiol. Other important cannabinoids in the plant include tetrohydrocannabivarin (THCV), cannabinol (CBN) and the acid forms (THC-A, CBD-A) found in raw cannabis.
Knowledge about and interest in CBD and other cannabinoids and terpenoids is relatively new but important for us as scientists learn more about them. CBD is the most readily available, non-psychoactive component that has anti-inflammatory, anti-oxidant, and neuroprotective properties. While potent marijuana today might contain a 50:1 or even as high as 250:1 ratio of THC to CBD, clinicians are now suggesting that plants bred to be “CBD rich”, with ratios of 1:1 or 2:1 CBD to THC ratio – or higher, such as 15:1 – might be useful for Parkinson’s while also being less psychoactive. GW Pharmaceuticals in Great Britain has a 1:1 blend called Sativex (legal in Europe, Canada, and perhaps soon in the US) that is being used now for multiple sclerosis spasticity and is likely to be approved for some pain management. Their Epidolex blend, almost pure CBD, is being used for several forms of childhood epilepsy. And their research is continuing (including for PD).
Besides using different strains of cannabis, different methods of using cannabis other than simply smoking, such as tinctures, oils, or edibles (such as cookies or candy) that are longer-lasting are becoming more common for medical uses. While smoking may take effect almost immediately and last 1-2 hours, a cannabis oral spray tincture or concentrated oil (both used under the tongue) may take effect in 15 minutes and last 7-8 hours, and ingested cannabis may take about an hour to take effect but also last 7-8 hours. How often cannabis is used may also be important – whether used as needed, one daily dose, or smaller doses several times a day to maintain a more even level in the body.
Marijuana varies greatly in terms of its potency and its composition. For research purposes, the best and most useful information will come from lab-tested cannabis whose potency and composition is known. Cannabis growers can get their cannabis composition analyzed by a reputable laboratory for about $100. Some labs test for other components besides THC and CBD, such as THCV and terpenoids, which will become more important as research continues. Some also test for pesticides and other contaminants.
Cannabis and Parkinson’s Disease
So how does cannabis relate to Parkinson’s?
The US Department of Health and Human Services, in 2003, got a ‘patent’ for “Cannabinoids as antioxidants and neuroprotectants,” and lists Parkinson’s as one of the diseases for which they expect it to be useful.
“It is the object of this invention [italics are mine] to provide a new class of antioxidant drugs, that have particular application as neuroprotectants, although they are generally useful in the treatment of many oxidation associated diseases. Yet another object of the invention is to provide a subset of such drugs that can be substantially non-toxic even at very high doses, and have good tissue penetration, for example crossing the blood brain barrier. It has surprisingly been found that cannabidiol and other cannabinoids can function as neuroprotectants.” [US patent 6630507]
Although cannabis has not been shown to replace the lost dopamine, it has been used by some people to alleviate some symptoms or perhaps boost the existing medication to make it more effective. As scientists learn more about the components of cannabis and how they work in the brain and interact with the neurotransmitters involved in Parkinson’s, this may allow much better use of cannabis for specific symptoms.
Cannabis, especially the cannabidiol (CBD) component, also appears to have neuroprotective properties which might slow the progression of PD. There is evidence of this in the laboratory but there are few studies and so far no long-term double-blind studies in humans. If cannabis is neuroprotective, how does that work? This is a key area for future research but that is not much help to guide patients now.
Many of the non-motor effects of Parkinson’s – anxiety, insomnia, depression, pain, weight loss, and nausea – are not unique to that disease. There is already much experience with cannabis use for those symptoms (ah, the munchies…) and Parkinson’s patients have benefitted from that experience for years and continue to experiment with what works for them. As we learn more about high-CBD strains, this may help even more. Cannabis may also work to relieve symptoms for which there is little that is effective at present, such as apathy or lack of motivation, and improve activity levels and quality of life. Improving non-motor symptoms such as sleep, anxiety, and pain is important because that can in turn improve motor symptoms.
Although at this time high-CBD blends seem to be the most likely basis for PD treatment, physicians currently do not appear to agree on composition (CBD, THC ratios) or dosage as they recommend cannabis to PD patients. More feedback from patients, as well as more research, is needed.
Studies and Anecdotes
There is a dearth of relevant human studies on cannabis and PD and many are limited, incomplete, and have flaws and contradictions. Some researchers avoid PD because it is not a simple disease. Many existing studies focus on symptoms rather than the much needed longer, more difficult neuroprotection studies. But they do also give tantalizing bits of information that can help guide future research. There is a recent Israeli study with 22 people smoking that appeared to show that cannabis reduced tremor, rigidity, bradykinesia (slowness), and pain, and improved sleep. An older Czech study of 85 people eating an unknown type of cannabis (both green and dried) with meals found an improvement in bradykinesia, tremor and dyskinesias in people who used it for 2-3 months. A 2009 Brazilian study shows CBD to be effective for psychosis in PD and a small 2014 Brazilian study shows CBD can reduce or eliminate REM sleep disorder.
There are studies at the cellular level and in mice and rats that point to various cannabis components as having good potential for not only helping symptoms but also for slowing down or perhaps stopping the progression of PD. There is interesting research in Spain, Israel, U. K., and Brazil among other places.
Anecdotes are just anecdotes, but they abound. Some anecdotes (many about high THC cannabis that was all that was available until recently, some about high CBD strains): 1-2 puffs would pretty reliably ‘kick in’ the levodopa when it didn’t seem to come on as it should and would make the tremor disappear; a cannabis brownie decreased or eliminated bad anxiety at night that greatly disrupted sleep for both the patient and her husband; “more energy, more motivation, fewer naps;” “more mental clarity;” “increased energy, enhanced mood, less bradykinesia, less stiffness, less gait disturbance, less apathy;” “decrease in REM sleep disorder;” “more [afternoon] wakefulness;” “helps dystonia cramping;” “less off-on variation, more even levodopa levels.” All this is welcome in a progressive disease that can impact the quality of life.
Until now patients have experimented on their own, generally without any guidance from their traditional physicians or scientific studies. Cannabis-recommending physicians and dispensaries often have limited experience with the complexity of PD. We hope to help change that – and learn from all those experiments PD patients are and have been doing. The Parkinson’s-Cannabis Project is conducting a survey of people with Parkinson’s who are using, or have used, cannabis to help with their PD. We hope to compile a large data base to discover for what symptoms cannabis may be useful (or not), in what types of people, with what quantities and proportion of THC and CBD (and other components as more are identified and tested in labs), how administered, at what dosages, and with what side-effects.
As knowledge about the various components of cannabis increases – and spreads both within the cannabis world and also to the general population – we hope to also discover what types of cannabis may be most effective for any given symptom. We have some guidelines from benefits that non-PD people have already found for these symptoms but the response in people with Parkinson’s may be different.
This is a self-reporting survey. It is therefore subjective but patients know how different medications affect their bodies and their lives better than a doctor will ever know. We have a questionnaire for people with Parkinson’s that asks many details about the person’s Parkinson’s history, symptoms, and what traditional medications they are using as well as their cannabis use. In the interest of getting the most useful information we are encouraging respondents to find out more about the cannabis they are using (by using lab-tested cannabis) and give us that information but we welcome responses from anyone regardless of how much information they have. Ideally we would like to know percentages of THC, CBD, and other components the labs might test for, as well as specific amounts. We will be surveying people with PD who we find through Parkinson’s support groups, physicians recommending cannabis, and word of mouth. We hope we will also get some referrals from physicians less familiar with cannabis who want to help their patients using all available tools. We began in California but hope to reach people across the country. We need as many participants as possible!
This is not a double-blind comparative study comparing cannabis to other medications although we may get some information on that as patients make their individual comparisons and vote with their feet on what works best for them, with the least side-effects. This is also not meant to study neuroprotection since a good study would require a long-term double-blind study. But it may inspire others to do that study – and to do it in a more informed way. We hope that this project may also serve as a model for other disease studies. We expect to complete the survey early in 2015, with some preliminary results before then.
While scientists seek to find more precisely how cannabis works and how it interacts with the dopamine receptors involved in PD, we hope that by looking at the experiences of a large number of Parkinson’s patients we may learn about how cannabis actually affects people with PD. We also hope that we may learn some hints about how cannabis works and how it interacts with dopamine that may be of use to researchers.
Theory and Practice: Questions and Cautions
The complexity of Parkinson’s, experience, and studies on the effect of cannabis for other diseases raises some specific questions for PD.
We begin with the assumption that cannabis may affect different people with PD in different ways. Will cannabis work the same for those in the early stages of the disease when the body can still produce a certain amount of dopamine as in later ones when the body’s own ability to produce dopamine is minimal? Will people in very early stages of the disease be able to put off levodopa and use cannabis alone, with fewer side-effects than traditional options such as dopamine agonists or anti-cholinergics?
Will cannabis work differently in people with different types of PD, people whose primary symptom is tremor or those whose primary symptoms are gait problems and rigidity? Parkinson’s has some symptoms that seem almost opposite. Will cannabis help reduce tremor or the involuntary dyskinesias that often appear in later stages and also rigidity? If so, this would support the idea that cannabis has a modulating or regulatory effect but does that match peoples’ experiences? GW Pharmaceuticals’ Sativex blend (1:1CBD/THC, legal in Europe and Canada and perhaps soon in the US) seems to show benefits for spasticity in multiple sclerosis. Their Epidolex blend (almost pure CBD) works well for some limited forms of epilepsy. How would those blends work for Parkinson’s tremor, dystonia, or dyskinesias? What would they do for people who experience gait problems or rigidity instead of tremor? There are probably other blends (components, proportions) that might meet PD needs better but what are they? Will cannabis work differently for those who appear to have an identified genetic link and will it vary with specific genes? How about for people exposed to various pesticide or solvents?
Does cannabis produce side-effects similar to those we see with traditional medications or does it avoid them by working in different ways? Dopamine agonists, for example, can cause hallucinations, sleep attacks, and various compulsions, such as gambling, shopping, eating, or hyper-sexuality. Anti-cholinergics such as trihexyphenidyl (Artane) can cause confusion and memory loss. Some medications can cause constipation, urinary retention, dry mouth, or hallucinations. High CBD blends may avoid potential cognitive problems that high THC can sometimes cause for some people.
Cannabis seems to be useful for decreasing motility in Crohn’s disease. Does that mean it will lead to more constipation for PD patients who already have that problem? Or if cannabis relaxes the muscles, would that help constipation? There is evidence for CBD as an anti-psychotic. Many anti-psychotics work by reducing excess dopamine. Does that mean it will also decrease scarce dopamine in PD, which is not at all what people with Parkinson’s need – or will it not work that way in PD? The limited evidence available indicates that CBD used to reduce psychosis does not increase motor symptoms. There is also evidence that CBD can help lower or eliminate REM sleep disorder (acting out dreams). Will this hold up in larger studies? Or, perhaps more important, will it work for any given person? And at what doses?
Can cannabis reduce the amount of carbidopa/levodopa or other adjunct medications required and, if so, with fewer side-effects? Might cannabis help those medications to be more effective? In later stages of the disease, PD patients may have a hard time navigating between too little medication which allows more symptoms or too much dopamine from medications which causes dyskenesias. Will cannabis work in ways that may avoid that dilemma of how to avoid getting either too little or too much dopamine? Can cannabis smooth out the ‘off-on’ effect’? How will cannabis affect some symptoms that appear to (at least sometimes) be levodopa dose-related, such as dyskinesias or REM sleep disorder? Can cannabis smooth out the ‘off-on’ effect? Will cannabis intensify the effect of dopamine or will it modulate it or neither?
Since THC and CBD (not to mention the more minor components) seem to have different mechanisms of action, how important is the composition of the cannabis being used? What works best for what symptom? How important is the “entourage effect” where the synergy of various components, including terpenoids and flavonoids, enhances the total effect? And what are the important components for PD? Does cannabis have different effects on various PD symptoms, such as motor symptoms or mood, at different doses? Some compounds of cannabis have different – even opposite – effects at different dosages. What components and doses are optimal for different PD symptoms – and for neuroprotection?
What is the best method of ingestion for people with PD (smoking, sub-lingual spray tincture or concentrated oil, or edibles)? This is especially relevant since digestion is often slowed with PD and regular PD meds compete with food protein for absorption in the small intestine. Will this matter? Does timing of cannabis in relation to other PD meds matter? Might different mixtures be better for day or night use?
As physicians make recommendations to PD patients, they will hopefully be aware of the whole range of PD problems, even if one symptom is the primary focus at any given time. It will also be important to watch for potential conflicting effects of different components of cannabis (THC, CBD) and to be alert for any potential side effects that might be specific to PD.
It is likely that as we get more answers, we may be able to tailor cannabis recommendations to better fit individual needs. How narrowly focused these recommendations will need to be is still unknown.
To Be Of Use
So much of this is theoretical because the brain is such a complex organ and we still don’t understand all of how it works. And Parkinson’s is a complicated and varied disease that is not fully understood. And how cannabis (with its many components) works is also still not fully understood. So that brings us back to the Parkinson’s-Cannabis Project in the hope that it can add to our understanding.
As part of this project, we hope to educate people with Parkinson’s (and physicians) more about cannabis and its components in order both to get better data and also to improve the effectiveness of cannabis for them. We hope that more cannabis will be lab-tested by more reputable labs around the country. We hope cannabis researchers and traditional PD researchers will interact more. And let’s all hope cannabis will soon be removed from the Schedule I drug list which will make all research easier and better.
For more information, or to participate in the survey, contact:
Helen Garvy , Parkinson’s-Cannabis Project
326 San Juan Ave., Santa Cruz, CA 95062
firstname.lastname@example.org (831) 426-1972