Evidence for the cannabis plant’s healing power is mounting high. After tireless campaigning from countless families of suffering patients, the UK has finally seen progression in the legal status of medicinal cannabis.
Modern medicine is beginning to accept and appreciate this historic plant; we are already seeing cannabinoids transform the lives of people living with severe conditions.
There is still far to go; much of the research remains in its infancy, but experts are cautiously optimistic. One of the more advanced and triumphant avenues of cannabis research is in the management of severe seizures – could cannabis revolutionise the treatment of epilepsy?
Epilepsy: an overview
Epilepsy is a chronic neurological disease where patients exhibit recurrent and debilitating seizures. The disease tends to affect more vulnerable age groups, such as children and the elderly. In the UK, there are currently over 600,000 people living with epilepsy – that is 1 in every 100 of the population.
Seizures can vary in severity, depending on which areas of the brain are affected; they manifest themselves differently in every patient. A seizure will broadly fall into one of two categories: focal, occurring in only one side of the brain, or generalised, where both sides of the brain are affected and consciousness is lost. Within these categories, there are further seizure types, classified by the International League Against Epilepsy (ILAE) in 2017.
Patients receive a diagnosis of an epilepsy syndrome if they display a particular set of symptoms or triggers that are consistent with specific criteria. Examples of childhood epilepsy syndromes include Dravet syndrome and Lennox-Gastaut syndrome – both of which are particularly resistant to current treatments.
How does the NHS treat epilepsy?
Epilepsy has proven to be a complex condition to manage. There has been very little progress in terms of identifying a generalised cure. This is because a ‘one size fits all’ approach to treatment is often not applicable to the vast array of seizure types and syndromes. Many patients require a unique cocktail of drugs to control their seizures.
The first approach to treatment on the NHS is anti-epileptic drugs (AEDs). These aim to alter brain activity so that the frequency of seizures is significantly reduced. Common AEDs include:
- Sodium valproate
- Benzodiazepines e.g clonazapem
- Barbituates e.g phenobarbitone
There is a variety of AEDs, each of which has shown to be effective against specific seizure types, but these drugs are hugely limited by their adverse effects. According to the NHS, common side effects of AEDs include:
- Hair loss
On top of this, sodium valproate can be detrimental to embryonic or foetal development, so can only be prescribed in women alongside contraceptive medication. Benzodiazepines have unwanted sedative effects and a potential for tolerance, and barbiturates have a high potential for abuse and dependence. So, despite being effective drugs, these AEDs are reserved for very specific cases and are unsuitable for a large number of patients.
Though perhaps the greatest limitation of current epilepsy treatments is that they are ineffective in up to a third of all patients. There are over 60,000 children under the age of 18 living with epilepsy in the UK, 23,000 of whom do not respond to treatment. These people and their families need a revolution in epilepsy therapeutics – could cannabis be the answer?
Medicinal cannabis and epilepsy
The Cannabis sativa plant has a long history of medicinal use. Its therapeutic properties are attributable to its two major cannabinoids, cannabidiol and tetrahydrocannabinol – more commonly named CBD and THC.
THC is psychoactive. It directly activates cannabinoid receptors across the brain and body, and is responsible for causing the characteristic mind-altering ‘high’. CBD, however, is non-psychoactive and has a more indirect mechanism of action. When they enter the body, either together or in isolation, CBD and THC have widespread therapeutic action and have even been shown to benefit patients living with epilepsy.
The effect of THC-rich cannabis products on epilepsy is inconclusive. Several studies have highlighted a significant reduction in seizure frequency with whole-plant cannabis use, but others have produced more mixed results. A review of the effectiveness of THC in animal models of seizures found that it reduced seizures in 62% of studies, induced seizures in 3%, had a mixed effect in 3%, and had no effect in 32%.
However, in a study of CBD-rich cannabis, with a 20:1 ratio of CBD:THC, seizure frequency was reduced by 89%. Far more research is needed to fully understand how cannabis could impact those living with epilepsy, but many scientists believe CBD or CBD-rich cannabis to be a valuable tool in epilepsy treatment.
On November 1st 2018, cannabis medicines were legalised in the UK. Doctors on the General Medical Councils (GMCs) specialist register are now permitted to prescribe cannabis to manage seizures.
Is cannabis a safe treatment for epilepsy?
Whilst there is growing evidence for the effectiveness of cannabinoids in the treatment of epilepsy, many researchers urge caution about the potential risks and adverse effects of cannabis – particularly in those who choose to self-medicate.
THC has been shown to have negative side effects in some people. These could include drowsiness, confusion, anxiety, and impaired motor coordination. However, it is argued that the rare side effects of cannabis are still far milder and less dangerous than current AEDs.
It is also not understood how long-term high-dose cannabis use could impact brain development in young people. Considering that children constitute a large number of treatment-resistant patients with epilepsy, this is a necessary area of future research.
The British Paediatric Neurology Association (BPNA) states that medicinal cannabis should be used in children who have seizures that are resistant to at least two AEDs and who have not responded to any other interventions.
Despite this, there are still many people living with drug-resistant epilepsy who have restricted access to cannabis medicines. In the three years that medicinal cannabis has been legal in the UK, only three NHS prescriptions have been issued. Researchers have argued that this causes ‘serious challenges in [the] day-to-day life’ of patients and families affected by epilepsy.
CBD and epilepsy
CBD, since it is a well-tolerated and non-psychoactive cannabinoid, is an ideal candidate for the treatment of epilepsy – especially in children.
In 2019, Epidiolex was approved for use in the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. It is an oral CBD solution (99% CBD, 0.1% THC) and has been shown to be hugely beneficial to young people living with epilepsy.
There is solid evidence for the effectiveness of CBD in the treatment of drug-resistant epilepsy. The data comes from three double-blind placebo-controlled trials, which are understood to be the gold standard of experimental design.
In the first study, 120 young people with Dravet syndrome were given either a 20 mg/kg dose of CBD or a placebo for 14 weeks. Seizure frequency halved in 43% of the CBD group, compared to only 27% in the control group. Six participants in the CBD group were even seizure-free at the end of the trial.
The second study administered either 10 mg/kg or 20 mg/kg CBD doses or a placebo to 225 patients with Lennox-Gastaut syndrome for 14 weeks. 42% fewer seizures were seen in the higher-dose group, 37% fewer in the lower-dose group, and 17% fewer in the placebo group; CBD appeared to have dose-dependant effects on seizure frequency.
The third study found similar results. Participants with Lennox-Gastaut syndrome experienced a 44% reduction in seizures when taking a 20 mg/kg dose of CBD for 14 weeks, compared to 22% in the placebo group.
How does CBD work?
Scientists believe that CBD can reduce the severity of epilepsy through its anti-inflammatory and neuroprotective properties. CBD has multitarget effects; it can modulate the activity of numerous receptors, membrane channels, and neurotransmitters, which is thought to balance the ‘excitability’ of the brain and reduce the likelihood of a seizure.
Much more research is needed before researchers will fully understand how CBD works, but since it has such a broad mechanism of action, CBD is believed to be closer to a ‘one size fits all’ treatment than current AEDs.
Taking CBD for epilepsy
For patients taking CBD in the form of Epidiolex, the recommended starting dose is 2.5 mg/kg twice per day. The dose can then be increased to 5-10 mg/kg twice per day if necessary.
CBD is available to legally buy online and in health shops in the form of oils, pills, capsules, and other CBD-based products. However, these products are not licensed, pharmaceutical-grade medications; there is no guarantee of their purity or whether they are suitable for use in patients with epilepsy.
It is important to do your own research if you choose to use CBD for medical reasons. Do not make any abrupt changes to your medication and always speak to your doctor if you are keen to explore the benefits of cannabis-based medicine.
Are there any risks or side effects?
With CBD being non-psychoactive, its reported side effects are far milder than with THC. These could include:
- Tiredness and fatigue
- Lower appetite
- Nausea and sickness
In rare cases, CBD has been shown to increase seizure frequency. Epilepsy is an unpredictable disease, so it is crucial that any new medications are monitored by a professional.
CBD appears to be safe and well-tolerated in children with epilepsy. In research published in Drug Science, Policy and Law in 2021, families of children living with epilepsy reported that cannabis medicines ‘allowed them to reduce the number of other AEDs prescribed, and that [they] also improved the often severe, side effects of various AEDs’.
CBD has, however, been shown to interact with some medications. In particular, there is a clinically relevant drug interaction between CBD and clobazam, a benzodiazepine. Again, speak to your doctor before trying any cannabis-based medicines to avoid any interactions between CBD, AEDs, or any other prescription drugs.
Despite the remarkable progressions in cannabis research, access to these potentially life-changing treatments is still restricted in the UK. The ongoing End Our Pain campaign hopes to change this; campaigners are striving to remove the barriers that are preventing children with epilepsy from receiving a medicinal cannabis prescription. They have one end goal, and that is to improve the quality of life for thousands of patients.
from leafie https://www.leafie.co.uk/articles/cbd-cannabis-epilepsy/