Amyotrophic lateral sclerosis (ALS) is a disease characterized by extensive damage over time to motor neurons in the brain and spinal cord. Motor neurons are nerve cells that are responsible for the communication, the signals, taking place between the brain and the muscles.
Due to this damage, the brain is increasingly unable to control muscle movement, and patients progressively loses the ability to easily do activities that most people take for granted, like walk, swallow, or speak. There is currently no cure for ALS, but treatments can help manage its symptoms.
One potential treatment is cannabis sativa, otherwise known as marijuana. Cannabis, as medical marijuana, is being assessed in its various forms for its potential in easing ALS symptoms.
How cannabis works
The active ingredients in cannabis — tetrahydrocannabinol (THC) and cannabidiol (CBD) — are called cannabinoids. They are believed to work as antioxidants and as anti-inflammatory and neuroprotective agents, and for these reason might slow or prevent further damage to nerve cells in ALS.
Both CBD and THC mainly function by binding to the cannabinoid receptor proteins CB1 and CB2 of the endocannabinoid system. The endocannabinoid system is responsible for regulating brain function, hormone secretion, and the immune system. CB1 receptors are present on the surface of nerve cells in the brain and spinal cord, and regulate neurodevelopmental activities; CB2 receptors are predominantly present in immune cells, and modulate inflammation and immune cell function.
Binding of THC to the CB1 receptor activates the receptor’s anti-glutamatergic action, meaning it inhibits the release of excess glutamate by nerve cells. Glutamate is a neurotransmitter, and in excess can cause nerve cell damage or excitotoxicity. In ALS, excitotoxicity is thought to compound nerve cell damage and increase neurodegeneration.
Since THC prevents excitotoxicity via the CB1 receptors, treatment with THC may be neuroprotective for ALS patients. A study showed that neuronal cells obtained from the spinal cord of ALS mouse models and treated with THC were protected from induced excitotoxicity.
The cannabinoids exert an anti-inflammatory effect through the CB2 receptors, which regulate immune cells and the production of inflammatory proteins. In this way, they might slow further tissue damage.
Cannabinoids also function as an antioxidant, but in a CB receptor-independent manner. Other receptors, such as the transient receptor potential vanilloid receptor 1, have been found to be involved, but how they work in ALS is still unclear.
Medical marijuana in clinical trials
Cannabis-derived products are being, or were, evaluated for their potential in treating ALS in various clinical trials.
Sativex (nabiximols), being developed by GW Pharmaceuticals, is an oral spray containing the two active components of cannabis. A Phase 2 trial (NCT01776970) in Italy, called CANALS, evaluated the safety, efficacy, and tolerability of Sativex in ALS patients affected by spasticity, or muscle stiffness. A total of 59 patients, ages 18 to 80, were included in the study. Patients were randomly assigned to receive either Sativex (29 patients) or placebo (30 patients). The study’s findings showed that Sativex was well-tolerated with no serious side effects. Spasticity was significantly reduced in treated patients compared to those given the placebo, whose symptoms continued to worsen.
An earlier single-site study (NCT00812851) tested the efficacy of oral THC in alleviating cramps in ALS patients. This was a crossover study, meaning that all 27 patients enrolled, (mean age 57; with moderate to severe cramps) were given THC at some point during the trial. They were randomly divided into two groups, one receiving 5 mg THC twice daily for two weeks, followed by a placebo; and the other receiving placebo first followed by THC for two weeks. A two-week treatment-free, or washout, period preceded changes in treatment status, and patients were evaluated two weeks after their treatment period.
This trial’s primary goal was changes in cramp intensity. The number of cramps per day, the intensity of muscle twitches, change in appetite, depression, and patient’s quality of life and sleep were measured as secondary goals. Study findings failed to show effectiveness in these measures; THC at 5 mg did did not alleviate cramps in ALS patients, and no significant changes were observed in the secondary outcomes, its researchers reported.
An ongoing Phase 3 study (NCT03690791) is testing the effects of CBD oil capsules by CannTrust on slowing disease progression in ALS patients. The study aims to enroll 30 patients, ages 25 to 75, who will be randomly grouped to receive either the CBD oil capsules or a placebo. In this six-month study, changes in a patient’s motor abilities, lung function, pain and spasticity levels, and quality of life will be assessed to evaluate the efficacy of CBD capsules. Enrollment at this trial’s single site, the Gold Coast Hospital and Health Service in Australia, may still be underway; contact information is available here.
In an observational study (NCT03886753), researchers at Children’s Hospital of Philadelphia are evaluating the effects of four formulations of cannabis-based products — the medical marijuana products Dream, Soothe, Shine, and Ease — by Ilera Healthcare used as standard therapy by people with multiple diseases, including ALS. How this therapeutic moves within the body (its pharmacokinetics) and its chemical interaction in the body (pharmacodynamics) will be monitored, and reports of relief of symptoms collected. The study is enrolling patients, ages 2 and older.
Another large and observational study (NCT03944447) in people with multiple diseases, including ALS, aim to assess the safety and efficacy of cannabis use by up to 10,000 people in the more than 38 states that have legalized medical marijuana. As an observational study, medical cannabis as part of person’s standard therapy — regular use — is being evaluated through patient reporting of perceived relief and findings of side effects.
Called OMNI-Can, the study and its investigators will use an anonymous online questionnaire to assess the potential benefits and side effects of medical cannabis on participants, most of whom are expected to be current users. A separate cannabis-naive group, defined as no use in the past year, will also be enrolled. Participants will first be given the survey at a visit with a physician to establish their baseline (start of the study) characteristics. Subsequent surveys will be given follow-up visits every three months for up to five years.
The study’s primary goal is the perceived benefits of cannabis in treating chronic pain, and the safety of its use via reporting of adverse events. Its impact on patients’ quality of life will be also be recorded, as will preferences such as favored type for use (route of administration, like vaping or eating as a candy) and its formulation (THC/CBD ratio). Contact information is available here.
Cannabis use should be in consultation with a treating physician, who can monitor patients for behaviors that may indicate dependence.
CBD, one of the more than 100 pharmacologically active compounds (cannabinoids) that can be retrieved from the cannabis plant, is thought to hold the greatest therapeutic potential. This is largely because it does not have the psychoactive properties common to other cannabis-related compounds. psychoactive properties
In addition to dependence, side effects attributed to medical marijuana use include lung irritation (smoking or vaping), low or elevated blood pressure, anxiety, dry mouth, changes in appetite, and nausea.
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