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Cannabis and epilepsy

There is growing interest in the general population for the use of cannabis for the treatment of seizures. News stories have appeared that have highlighted that some parents have been forced to source medical cannabis from overseas for their children with severe epilepsy. In April 2019, a mother attempting to illegally bring medical cannabis into the UK in a bid to help her daughter who experienced up to 300 seizures per day broke down in tears as border officials seized the cannabis at the airport. You can find the story here. This is not an isolated story and there are calls for laws and regulations to be relaxed so that more people with epilepsy can be treated with medical cannabis. 

It has been reported that medical cannabis can help selective patients with extremely severe childhood epilepsy. Some evidence demonstrates that the number and severity of childhood refractory seizures can be reduced when cannabidiol – one of over 100 components of marijuana – is used alongside standard anti-seizure medications. One study in the New England Journal of Medicine reported that the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional anti-seizure medication regimen resulted in greater reductions in the frequency of drop seizures compared to placebo. Such findings have generated a lot of interest by patients with epilepsy and their families and carers.

It is important to consider the following:

  1. Cannabidiol in it’s own right is not a cure for seizures. For most patients, it does not stop or prevent seizures when taken alone or even with other medications. The scientific evidence indicates that it can reduce the severity and frequency of some kinds of seizures when standard anti-seizure medications are used. It is very rare for cannabidiol, when used with other anti-seizure medications, to stop seizures altogether. 
  2. There is only evidence to suggest that when cannabidiol has any seizure-reducing effect, it does so only in some children with very particular, severe and rare epilepsies. There is very little existing evidence to support its use in adult epilepsy.
  3. Most of the clinical trials that have examined the effects of cannabidiol on seizures have also reported significant side effects. The above paper in the New England Journal of Medicine reported greater side effects in the patients taking cannabidiol compared to placebo, most notably elevated liver aminotransferase concentrations. Vomiting, loss of appetite and diarrhea may also occur. The risk of potential side effects are, of course, associated with all anti-seizure medications. 
  4. There are few replication studies reporting the same kind of efficacy; replication studies are crucial for the development of disease-treating medications. 
  5. To date, the exact neurobiological and molecular mechanisms of action of cannabidiol and how these mechanisms may reduce seizures are not entirely understood. There are three targets proposed: transient receptor potential vanilloid-1 (TRPV1), the orphan G protein-coupled receptor-55 (GPR55) and the equilibrative nucleoside transporter 1 (ENT-1). However, not knowing how drugs work does not mean that they cannot be used to treat epilepsy. The first clinical use of phenytoin, ethosuximide and carbamazepine to treat epilepsy was 1912, 1958 and 1963, respectively. Their respective mechanisms of action were not understood until 1979, 1989 and 1983. Indeed, the exact mechanisms of action of sodium valproate, which was first used to treat epilepsy in 1967, are still not fully understood. 
  6. Cannabidiol is only one of over 100 components of marijuana. Marijuana also contains the psychoactive component THC (Tetrahydrocannabinol). THC is responsible for the ‘high’ or euphoria people experience when taking marijuana. Cannabidiol and THC have the same molecular structure, are chemically similar to your body’s endocannabinoids, and encourage the release of neurotransmitters in the brain. However, THC but not cannabidiol binds with the cannabinoid 1 (CB1) receptors in the brain; it is this mechanism that gives people the ‘high’. Cannabidiol does not give the psychoactive effects that THC does. 

There are plenty of reputable and scholarly online resources to read about the use of Cannabidiol to treat seizures. It will be interesting for patients to understand the perspectives of doctors who are treating epilepsy. One such article provides a nice overview of options, evidence and clinical practice. 

Ultimately, incorporating cannabidiol into clinical care of people with epilepsy needs to be informed by reliable empirical evidence, like all new medications. There is preliminary scientific evidence indicating that it could be helpful in selected children with very severe genetic epilepsies. This does not mean that this treatment option should be rolled out to anyone experiencing seizures.

Dr Simon Keller

 

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