Can Cannabis Help ALS?
ALS (Amyotrophic Lateral Sclerosis) is a terminal neurodegenerative disease in which damage to motor neurons causes progressive muscle wasting and weakness. With a life expectancy after diagnosis of between 3-5 years, current medication aims to ameliorate ALS symptoms such as muscle spasms and twitching, albeit with varying success. The hunt therefore is on to find drugs that not only improve ALS symptoms, but slow disease progression itself. Potentially promising contenders are compounds found in the cannabis plant.
All neurodegenerative diseases share at their root excitotoxicity (neuron damage caused by overactivation of glutamate receptors), oxidative stress (an imbalance between the production of free radicals and antioxidant defenses) and neuroinflammation (inflammation response within the brain and spinal cord). Current ALS drugs tend to focus on single elements, such as the glutamate antagonist riluzole which has limited therapeutic benefit and is only slightly more beneficial at increasing patient survival than a placebo.
The prospect that one drug could target all three contributing causes of ALS is of tremendous interest and could be a real game changer for ALS patients. For that reason, compounds in the cannabis plant, which are known to be anti-inflammatory, neuroprotectants and antioxidants, are currently being researched for the treatment of ALS. In fact, the US government holds a patent on cannabinoids for that very reason.
The Endocannabinoid System
Another reason cannabinoids are of particular therapeutic interest as potential ALS drugs is their ability to interact with and modulate the endocannabinoid system (ECS), which itself plays a role in the development of the disease.
The ECS comprises 2 key types of G protein-coupled receptors found on cell membranes. CB1 receptors are located mostly in the brain and central nervous system. Their distribution in the brain is particularly noticeable in areas related to motor coordination and movement, attention and cognitive function, plus learning, memory and emotions. CB1 receptors regulate the release of chemical messengers such as neurotransmitters, protecting the brain from overstimulation or over-inhibition.
CB2 receptors on the other hand, are found mostly on immune cells and tissues, although they have also been discovered in glial cells in the central nervous system. CB2 activation is thought to have an overall immunomodulating effect, controlling the release of cytokines, the proteins responsible for inflammation response regulation.
Binding with the CB1 and CB2 receptors are a class of lipid based molecules called endocannabinoids, principally anandamide (AEA) and 2-AG, which are produced on demand when there is some kind of biological imbalance. They are broken down by the enzymes FAAH and MAGL once their regulating work is done. All of which gives us a clue to the overall function of the ECS — to promote homeostasis or balance across all physiological functions.
In the paper, “Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system,” the authors describe how the ECS has the ability to modulate the key traits contributing to neurodegenerative diseases such as ALS, and is “thus, emerging as a viable target for symptom alleviation or disease progression based on pharmacological modulation of endocannabinoid signaling.”
Studies on ALS animal models and ALS patients show some ECS dysregulation in the brain and spinal cord. However, this may well be a sign of the ECS doing its neuroprotective work rather than the dysregulation itself being a cause of the disease.
In particular, raised levels of AEA and 2-AG were found in ALS mice models, as well as increased CB2 receptor expression in astrocytes at lesion sites and microglia in spinal grey and white matter areas in animal models and ALS patients.
However, an overall down regulation appears to occur in CB1 receptor expression, which may predispose subjects to excitotoxicity through excess glutamate.
Perhaps the most promising area of research in the development of drugs for ALS are agents that bind with CB2 receptors in the body. In one study on ALS mice, daily administration of a CB2 agonist delayed motor impairment and increased survival by 56%.
Cannabis & ALS
This brings us neatly onto the cannabis plant, which contains compounds that bind with CB2 receptors and has an overall modulating effect on the endocannabinoid system.
Within the cannabis plant can be found at least 144 compounds called cannabinoids, most notably Tetrahydrocannabinol (THC) and Cannabidiol (CBD), as well as a host of other organic compounds such as terpenes and flavonoids.
THC directly binds with both CB1 and CB2 receptors, having a neuroprotectant and anti-inflammatory effect. CBD on the other hand, does not activate either cannabinoid receptor, instead having a more indirect effect on the ECS by blocking the enzyme (FAAH) that degrades anandamide. Interestingly, one of the key areas of ECS modulation research is the development of FAAH inhibitor drugs which are thought to increase AEA levels in the body.
Thus, one can see then that compounds found within the cannabis plant may have therapeutic potential in the treatment of ALS through ECS modulation. Indeed, in one study, ALS mice were treated with THC before and after disease onset. Improvement in motor improvement was noted and disease survival increased, which was thought to be due to a reduction in excitotoxic and oxidative cell damage.
Before any concrete conclusions can be reached about whether cannabinoids are an effective treatment for ALS, scientists must make the leap to clinical studies on humans. Unfortunately, given the legal status of cannabis around the world until of late, conducting human trials on multiple forms of cannabis has been difficult, to say the least.
So far, the most promising has been a phase 2, double blind, randomised, placebo trial using Sativex (nabiximols) for spasticity in ALS.
Sativex a cannabinoid-based pharmaceutical drug with equal 1:1 ratio of THC to CBD has been approved to treat spasticity and pain in multiple sclerosis. 55% of ALS patients in the study reported overall improvements in spasticity and pain, compared with 13% in the placebo group. Furthermore, the drug was well tolerated with mild-moderate side effects including dizziness, lack of energy, and confusion. It is hoped these promising findings and acceptable tolerability profile will encourage a larger clinical trial at a future date.
A further clinical trial is currently recruiting in Australia, this time testing a CBD dominant oil on 30 subjects with ALS.
ALS (Amyotrophic Lateral Sclerosis) was discovered and named in 1896 by French neurologist Jean-Martin Charcot. ALS is also called Lou Gehrig’s Disease, after the baseball player Lou Gehrig, who was one of the most famous people to suffer from the disease. ALS is a motor neuron disease, meaning that it affects the nerve cells in the brain and the spinal cord that are responsible for controlling your muscles.
ALS is progressive, which means that the symptoms get worse over time. When you have ALS, your motor neurons weaken and die, leaving you with no way to control your muscle movements. Without any control, your muscles get weaker too. They twitch uncontrollably, a process called fasciculations, and then waste away. Most patients ultimately die as a result of the disease.
There are two types of ALS:
- Sporadic. This is the most common form of ALS. 90-95% of people who develop ALS have sporadic ALS. Sporadic ALS means that it affects someone without any apparent cause or warning.
- Familial. Familial ALS (FALS) is inherited. If you have familial ALS in your family, there’s a 50% chance that each child may inherit the disease.
The earliest symptoms of ALS are usually muscle stiffness, weakness, or twitches, which are easy to overlook. The first symptoms of ALS differ widely since they depend on which motor neurons are the first ones to be affected.
Some of the first symptoms of ALS include:
- Stiff fingers, hand, or arm muscles that make it difficult to button a shirt, write, or turn a key
- Weakness in the legs or ankles, stumbling and tripping more often than usual, feeling awkwardness when walking or running
- Slurred speech or difficulty swallowing
- Tight, stiff, cramped muscles
- Uncontrollable fasciculations (twitching) in your tongue, arms, legs, or other muscles
When ALS begins with slurred speech or trouble swallowing, it’s called Bulbar Onset ALS.
When it begins with fasciculations, stiffness, or weakness in your arms or legs, it’s called Limb Onset ALS.
Although the early signs of ALS are subtle and very similar to other, more benign health issues, as time goes on and more neurons die, the symptoms will grow more obvious. Weakness, fasciculations, and muscle atrophy will spread across the body. Over time, people with ALS can no longer stand, walk, get out of bed, or move their arms, legs, or head themselves. Most people with ALS lose the ability to speak, too, because the tongue muscles are also affected, and to chew and swallow.
Eventually, ALS affects the muscles that help you breathe. Most people with ALS end up needing a ventilator to keep them alive.
It’s important to note that ALS spreads in a different way and at different speeds for each person, so it’s impossible to predict exactly what will happen to each person diagnosed with ALS.
ALS does not affect your mental or cognitive ability. If you have ALS, you are still able to:
- Think, reason, and solve problems
- Use all of your senses, so you can see, hear, taste, smell, and feel things the same as usual
- Remember people, places, events, and experiences
A small percentage of people with ALS are also diagnosed with some form of dementia, language processing issues, or decision-making issues.
Familial ALS is a genetic disorder. In a family with a history of ALS, there’s a 50-50 chance that each child will develop the illness. But just having a single parent or family member who develops ALS doesn’t significantly raise your chances of getting it.
Researchers are still trying to identify what causes sporadic ALS. So far, the consensus is that it’s caused by a complicated combination of genetic and environmental factors.
Risk factors for developing ALS include:
- Age. The risk of ALS increases as you get older. Most people diagnosed with ALS are aged between 40 and 70.
- Gender. Men are slightly more likely to develop ALS than women, but as you age, the difference between the genders disappears.
- Race and ethnicity. Caucasians and Hispanics develop ALS more than people from other backgrounds.
- Genetics. Some researchers have found genetic variations in the genomes of people with Familial ALS and sporadic ALS, which hints that there could be an underlying genetic cause for ALS.
- Smoking. Smoking has been found to raise the risk of developing ALS, particularly in women who are post-menopausal.
- Exposure to environmental toxins. There’s some evidence that exposure to lead or other substances could be linked to ALS, but no study has identified a single agent or chemical.
Military veterans are 1.5 to 2 times more likely to develop ALS. The reasons behind this connection are still not clear, but it’s been suggested that veterans are exposed to more lead, pesticides, and other environmental toxins than civilians. The U.S. Department of Veterans Affairs recignizes ALS as a service-connected disease.
Diagnosing ALS consists of a neurological exam and a careful history from the patient looking for telltale signs of ALS including muscle fasciculations, weakness and no change in sensation. A full neurological exam will be accompanied by a nerve conduction study (EMG/NCS).
There’s no single test to identify ALS. Other tests are often performed to rule out other conditions.
Tests that are used to help diagnose ALS include:
Muscle and imaging tests
Electromyography (EMG), Nerve Conduction Study (NCS), and Magnetic Resonance Imaging (MRI).
- An EMG test detects electrical activity in the muscle fibers.
- NCS tests assess whether a nerve can still send a signal to a muscle or along the nerve.
These tests help rule out peripheral neuropathy, which is damage to the nerves outside of the brain and the spinal cord, and myopathy, which is a muscle disease.
An MRI test is used to rule out other causes like a tumor or cyst in the spinal cord, a herniated disk, or cervical spondylosis. People with ALS generally get normal results on their MRI scan.
Depending on your symptoms and the results of other tests, your doctor might order blood tests and urine sample tests to check for other diseases.
Tests for specific diseases and conditions
There are some infectious diseases which can cause symptoms that are very similar to ALS, so your doctor will consider them and test for them while making a diagnosis. These include HIV (Aids), West Nile virus, and human T-cell leukemia virus; multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, and Kennedy’s disease.
There’s still no cure for ALS. Most people with ALS die within 3 to 5 years of diagnosis, usually of respiratory failure, although some people live with ALS for 10 years or more.
However, there’s a huge amount of research going on into ALS, and researchers hope to eventually find a cure. For the moment, there are a number of ways to treat the symptoms of ALS, improve quality of life, and prolong survival.
Studies have found that participating in a multidisciplinary ALS clinic can prolong survival and improve quality of life. These clinics are staffed by teams that include physical, occupational, and speech therapists; doctors and nurses; pharmacists; home care and hospice workers; social workers; and respiratory therapists. Multidisciplinary teams prepare individual treatment plans, therapeutic activities, and medication, and suggest the right equipment to help people with ALS remain independent for as long as possible.
At the moment, 4 drugs have been approved to help treat ALS:
- Riluzole (Rilutek)
- Edaravone (Radicava)
None of them can reverse or cure ALS, but they can slow down muscle decline and prolong survival. Clinical studies are still ongoing, for these and other new drugs for ALS.
As well as these four medications, physicians can also prescribe medications to help with the symptoms of ALS. Different drugs can be given to ease cramped and stiff muscles, reduce excess saliva and phlegm, deal with the depression and anxiety that often accompany ALS, treat constipation and insomnia, and prevent involuntary and uncontrollable crying or laughing.
In the early and middle stages of ALS, physical, occupational, and speech therapy can help prolong independence and communication.
Physical therapists design a course of low-impact aerobic exercise to strengthen muscles that haven’t yet been affected and combat depression. They can also guide you in a range of stretches to prevent muscles from getting painfully cramped and stiff.
Occupational therapists guide people with ALS to choose the right equipment, like ramps, walkers, and wheelchairs, to help you remain mobile.
Speech therapists can teach new strategies to help people with ALS to speak more loudly and clearly despite the degeneration of related muscles. As ALS becomes more serious, speech therapists can help you to communicate through advanced technology like computer-based speech synthesizer, eye-tracking technology, and non-verbal communication.
Various alternative therapies like guided meditation can be used to help people with ALS ward off depression and anxiety, and maintain a positive state of mind.
People with ALS burn calories faster. This can easily lead to malnourishment, especially since people with ALS have trouble chewing and swallowing as the muscle weakness progresses. Nutritionists help caregivers and individuals to prepare frequent small meals that are high in calories, to prevent malnutrition, and to choose foods that are easy to swallow.
When the muscles that help you breathe start to get weaker, you’re likely to experience shortness of breath when exercising or find it difficult to breathe when lying down.
As breathing becomes more difficult, non-invasive ventilation uses a mask to help you maintain the right levels of oxygen and carbon dioxide in your bloodstream.
Therapists also help you try different techniques to cough, in order to keep your airways clear of phlegm and saliva.
Eventually, breathing support might be delivered through a respirator or a tracheostomy.