The case for (and against) cannabis
Cannabis, also known as marijuana or weed, is a psychoactive drug made from the cannabis plant. Although an illegal drug there is increasing interest in the potential therapeutic effects it may have for Parkinson’s. In this blog, we take a look at the evidence so far.
Barely a week goes by that we are not contacted by someone with Parkinson’s asking about cannabis. The debate continues on social media platforms like Facebook, Twitter, YouTube and the Parkinson’s UK forum. With such interest in the topic, it seems that some people with the condition are using it and some report benefits for their symptoms.
But what’s the evidence behind these personal stories?
First, let’s tackle the legal stuff.
Cannabis is a class-B controlled drug in the UK. Possessing, producing and supplying it are all against the law. ‘Supply’ includes sharing the drug with someone or giving it (even for free) to friends or relatives. The law doesn’t allow you to use as a defence the fact you were using cannabis for medical reasons.
The penalties if you are caught taking or dealing drugs - drug classification, fines and prison sentenceswww.gov.uk
There is currently one cannabis-based medicine — called Sativex — which can be legally prescribed and supplied under special circumstances in the UK. It’s a mouth spray that contains controlled proportions of two cannabinoids: THC and CBD (more on these later).
Back in 2010 the Medicines Healthcare Regulatory Agency (MHRA) approved Sativex as a treatment for people with Multiple Sclerosis who experience spasticity (severe stiffness). However, in 2014 the National Institute for Health and Care Excellence (NICE), who recommend which drugs can be made available on the NHS, decided Sativex doesn’t deliver sufficient benefits to justify the cost.
Complex combinations of drugs are sometimes needed to manage spasticity, but they do not work that well and have a…www.telegraph.co.uk
So far there have not been any clinical trials to test the safety and effectiveness of Sativex in people with Parkinson’s.
What is cannabis?
Cannabis has been used since ancient times and comes from the Cannabis sativa plant. It’s known to be a psychoactive drug which means that it affects brain function and causes changes in perception, mood, consciousness or behavior. It contains at least 85 complex chemicals called cannabinoids and 2 in particular are thought to be largely responsible for its effects:
- Tetrahydrocannabinol (THC) is the major psychoactive ingredient, acting primarily upon the central nervous system where it affects brain function.
- Cannabidiol (CBD) has mainly non-psychoactive properties and reduces the psychoactive effects of THC.
Our brain cells produce their own brand of these molecules called endocannabinoids which are thought to be involved in regulating a whole range of brain functions including memory, pleasure, concentration, thinking, movement and co-ordination, appetite, and pain.
The evidence so far
There is no doubt that cannabinoids are interesting biological molecules and play a variety of important roles in our bodies. As a result, there is a huge amount of research underway to understand more about this complex family of chemicals and their potential across a range of different illnesses.
We have 2 main types of cannabinoid receptor, CB1 and CB2, which are found throughout the body. When a cannabinoid attaches to one of these receptors on the surface of a cell it triggers a biological response.
CB1 receptors respond to THC and are found in the brain. These receptors are largely responsible for the infamous ‘high’ and psychoactive effects associated with using cannabis.
CB2 receptors respond to CBD. They are mostly found on cells involved in the immune system but are also found on some cells in the brain where they are believed to be involved in the relief of pain. They are also present on microglial cells which act as the first and main form of active immune defence in the central nervous system.
But these 2 cannabinoid receptors may not tell the whole story. Recent research has revealed that THC may also bind to other, non-cannabinoid receptors on the surface of brain cells, and that these interactions may produce quite different effects.
The complex and multiple roles played by these different types of cannabinoids throughout our bodies and brains are not well understood. Studies so far have revealed a wide range of interesting effects in the lab that could hold promise for Parkinson’s.
There are lots of cannabinoid receptors present in the brain areas involved in the co-ordination of movement. However, the role played by cannabinoids remains a mystery.
Experiments using animal models have produced varied and inconsistent results in terms of tremor, slowness and dyskinesia (uncontrollable movements) — which are all key features of Parkinson’s. In some circumstances cannabinoids appear to be helpful, in others they seem to make things worse.
These confusing results suggest that we still have a lot to learn about the role these chemicals play in controlling movement and how their effects may be harnessed to improve treatments for Parkinson’s.
Protecting brain cells
One of the most exciting features of cannabinoids as potential drugs is their wide variety of actions.
This is particularly important in neurodegenerative conditions like Parkinson’s where brain cells are struggling to cope with a range of problems including:
- protein misfolding — which produces misshapen proteins that build up inside cells
- inflammation — when the brain’s defence system becomes overactive and causes damage
- oxidative stress — when there is an overload of damaging molecules called free radicals
- mitochondrial failure—when the tiny energy-producing batteries that power our cells stop working properly
Lab studies have suggested that cannabinoids may influence all these processes. Most research has so far focused on the role of CB2 receptors in regulating inflammation, which is known to be increased in the brains areas affected by Parkinson’s. Some experiments testing drugs that target CB2 receptors in mice and rats like this study, from researchers at the United Arab Emirates University, have shown significant promise in protecting against Parkinson’s-like damage.
Alongside physical symptoms, Parkinson’s can have other symptoms ranging from depression and anxiety to hallucinations, memory problems and dementia. These symptoms can often be the most difficult to treat. However, cannabinoids have shown promise in tackling some of these other symptoms
Studies have shown that cannabinoids can have beneficial outcomes in rat and mouse models of anxiety and post-traumatic stress disorder but may have side effects (including anxiety) particularly when used in the longer term. But a recent review highlighted the potential of cannabinoids in depression, reward and pain control, which are all pressing concerns in Parkinson’s. However, when it comes to the effects on sleep, the evidence is mixed according to this review.
In general, research seems to suggest that cannabinoids themselves or drugs based on them could be a useful approach for some of these other aspects of Parkinson’s, but there is still a need for further research to understand how best to harness the beneficial effects while minimising the side effects.
What about studies in people?
So we’ve seen that cannabinoids have some interesting effects in the lab when tested in cells or animals like mice and rats, but the real test is to see if these effects can also be seen in people.
To date, there have only been a handful of small studies of cannabis-based treatments in people with Parkinson’s reported in the scientific literature which we’ve summarised below:
Pilot study — 1990
UK researchers conducted a very small study in 5 people with Parkinson’s with severe tremor. The participants were assessed by doctors before and after they “smoked marijuana as a cigarette”. None of the patients, including one individual who had previously reported benefit, experienced relief or improvement in their tremor. Read more
Patient survey — 2004
Researchers in the Czech Republic posted out 630 questionnaires to people with Parkinson’s in Prague. They received completed questionnaires from just over half of them and 85 people reported using cannabis.
Of these 85, almost half said they experienced some improvement in their movement symptoms after using cannabis. But, perhaps surprisingly, half reported no effect on their Parkinson’s, and 4 people found it made their symptoms worse. Read more
Surveys like this one can provide useful insights but they don’t meet the same scientific standards as properly conducted clinical trials. This means the results need to be treated with caution and do not stand up as evidence of the medical benefits.
So let’s take a look at 2 more trials now.
Dyskinesia study — 2004
A team of UK researchers ran a study to assess the effect of oral cannabis extract on dyskinesia in 19 people with Parkinson’s. Participants were randomly assigned to receive either oral cannabis extract for 4 weeks followed by a 2 week break and then a placebo for 4 weeks, or vice versa. This meant that all the participants received the oral cannabis extract for a 4 week period but they didn’t know when they were getting it. The participants’ levels of dyskinesia were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) and a variety of other measures including questionnaires and diaries.
The results were disappointing. Cannabis extract produced no improvement in dyskinesias or Parkinson’s symptoms in any of the measures. On the positive side, the treatment was well tolerated and there were no significant side effects. Read more
Exploratory study — 2014
More recently a team of researchers in Brazil conducted a study in 21 people with Parkinson’s who were divided into 3 groups: a placebo group, a group who received a dose of 75mg cannabidiol each day, and a group that received 300mg cannabidiol each day. It’s unclear how long the study ran for or whether the participants knew which group they were in.
The researchers assessed participants on a variety of measures and found that there was no difference in the groups in terms of Parkinson’s symptoms measured using the UPDRS and there was no evidence that cannabinoid treatment had a biologically neuroprotective effect. However, there was a significant difference between the placebo group and those who received 300mg per day in terms of quality of life — although it’s not clear from the abstract what aspects of quality of life improved. Read more
Both these trials failed to demonstrate that cannabis-based treatment delivers the kinds of benefits hinted at in the lab studies for people with Parkinson’s.
But they were both very small in terms of numbers of participants and quite short term, so you could certainly argue that we haven’t given cannabis a fair shot.
Larger and more comprehensive studies are needed and there is a phase 2 clinical trial currently underway at the University of Colorado in the US funded by the company GW Pharmaceuticals looking at the effect of cannabidiol on tremor in 50 people with Parkinson’s. Read more
Risks and side effects
As with any medical treatment, cannabis-based treatments also come with risks and side effects that need to be fully understood and weighed against the possible benefits.
A cochrane review published in 2015 looked at 79 studies using cannabinoids across a range of illnesses including chronic pain, depression, anxiety, multiple sclerosis and others. The authors found that cannabinoid-based treatments were associated with an increased risk of negative effects, including:
- physical weakness or lack of energy
- balance problems
- dry mouth
There are also other important factors to consider when it comes to safety:
What’s in your weed?
Cannabis comes in many forms, both natural and synthetic, and the levels of different cannabinoids (THC and CBD) can vary significantly. Research conducted in the US on drugs seized by the police suggests that over the past 2 decades the levels of THC in street cannabis have been rising which increases the risk of harmful reactions such as hallucinations, paranoia and psychotic episodes.
Smoking cannabis irritates the lungs and can cause breathing problems including coughing, more frequent lung illness, and a higher risk of lung infections. Cannabis use can also raise your heart rate and may even increase the chance of a heart attack. Older people and those with heart problems may be at higher risk.
In the past cannabis wasn’t thought to be addictive. However, research has shown that it can be addictive, and around 10% of regular cannabis users are thought to become dependent.
Endangering yourself or others
Like drinking and driving, driving under the influence of cannabis is illegal — and you can still be unfit to drive the day after smoking cannabis. You can get a heavy fine, be disqualified from driving or even go to prison.
Find out more about cannabis, the law and the risks here:
Confused about cannabis? From its various forms to its effects on the brain, you can get all the answers from FRANK.www.talktofrank.com
When it comes to research evidence, the jury is definitely out.
Although there’s been some promising effects shown in lab studies, there isn’t enough evidence to show that cannabis-based treatments are beneficial for people with Parkinson’s, and there are very real risks.
There are still many unanswered questions, including:
- What types or mix of cannabinoids are most beneficial?
- How can we minimise or avoid risks and side effects?
- Can cannabinoids help protect brain cells?
Answering these will require a lot more research both in the lab and ultimately in clinical trials.
Our policy panel will be meeting later this year to consider what the charity’s position on cannabis should be. If you would like to feed in your views on this topic please email them to email@example.com
This blog is not meant as health advice. You should always consult a qualified health professional or specialist before making any changes to your medications or lifestyle.