Could a compound found in cannabis treat epilepsy?

"Cannabis could be used to help treat epilepsy," the Mail Online reports. A leading epilepsy medical journal has published a critical review summarising the evidence of the benefits of cannabis – specifically the compound cannabidiols – in preventing seizures. The review highlighted one thing: the evidence does not point to any clear answers.

The summary of evidence had a significant risk of bias because it did not employ systematic methods to identify all the relevant information on the topic. It is unclear whether important evidence was overlooked or ignored.

Nonetheless, it reached cautious conclusions. The review included tentative evidence that components of cannabis may help convulsions in humans and mice, but this evidence was patchy and very weak, so may be wrong. There were also reports of the compound making convulsions worse, as well as other negative side effects. 

The Mail Online referred to a recent example where cannabis extracts were used successfully to reduce seizures associated with SCN1A-confirmed Dravet syndrome in a young girl called Charlotte.

But individual successful cases don't provide strong enough evidence to expose large amounts of people to unknown risks. 

There are a range of health concerns associated with cannabis use, especially in the young, so any potential harms related to its medical use need to be considered carefully and cautiously.

Where did the story come from?

The summary of evidence was produced by researchers from the Comprehensive Epilepsy Center at the New York University School of Medicine.

The review was adapted from a conference called "Cannabidiols: Potential use in epilepsy and other neurological disorders" sponsored by GW Pharmaceuticals, a company described as having a "commercial interest in developing cannabidiols for the treatment of epilepsy and other conditions".

Some researchers involved in the review also declared funding links with GW Pharmaceuticals and other drug companies, as well as academic funding grants.

The review was published in the peer-reviewed medical journal, Epilepsia.

The Mail Online covered the story as if something new had been discovered. This appears to be linked to a case report about a girl who used cannabis successfully to reduce her epileptic seizures.

However, the main body of the research published in Epilepsia was a more general summary of the current evidence on cannabinoids and their potential relevance to epilepsy or other neuropsychiatric disorders.

What kind of research was this?

This was a critical review and commentary that attempted to present a summary of the current scientific evidence about the cannabinoid cannabidiol (CBD) regarding its use in the treatment of epilepsy and other neuropsychiatric disorders.

D9-Tetrahydrocannabinol (D9-THC) is the major psychoactive ingredient in cannabis and CBD is the major non-psychoactive ingredient in cannabis.

Epilepsy is a condition that affects the brain and causes repeated seizures, also known as fits. It affects more than 500,000 people in the UK, meaning that almost 1 in 100 people have the condition. Epilepsy usually begins during childhood, although it can start at any age. 

This research does not report to be a systematic review, meaning there is potential that key research (published or unpublished) may have been missed out. This represents a bias that may have affected the conclusions drawn.

A systematic review would be a methodological improvement on this method, and is the most thorough and comprehensive way of reviewing a topic.

What did the research involve?

The report stated it was a summary of presentations from a conference where participants were invited to review relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects.

It was not clear if or how any additional evidence was compiled for the summary report. There was no description of the methods by which relevant literature on cannabis and epilepsy was searched or identified, and there was no mention of inclusion or exclusion criteria. As such, the summary appears to have been based solely on the conference presentations.

Because there was no systematic search of the literature available on the subject, there is a high risk of selection bias (cherry picking). This means relevant literature may have been missed, which could potentially lead to false conclusions.

What were the basic results?

The main points from the summary of the evidence included:

• Cannabis and D9-THC appear to help stop convulsions (uncontrolled shaking of the body caused by muscle spasms) in most animal studies, but can make convulsions worse in some healthy animals.
• In animal studies, CBD appears to help stop convulsions in the short term, but there haven't been many studies looking at its longer term use or effects.
• The biological mechanism by which CBD reduces seizures is not known, although there are many theories.
• CBD has neuroprotective and anti-inflammatory effects and appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.
• Recent anecdotal reports of high-ratio CBD:D9-THC medical cannabis have claimed to work, but these studies were not controlled. This means they did not have a comparison group, so other non-cannabis effects may have accounted for the benefits, or they may have got better on their own.

How did the researchers interpret the results?

The researchers concluded that, "CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischaemic encephalopathy."

But they went on to state that, "We lack data from well-powered double-blind randomised, controlled studies on the efficacy of pure CBD for any disorder."

Conclusion

The summary of evidence on the potential use of the active ingredients in cannabis to reduce epileptic seizures highlights one thing: the evidence does not point to any clear answers.

This summary also has a significant risk of bias because it did not employ systematic methods to identify all the relevant information on the topic.

Nonetheless, it reached cautious conclusions, highlighting the need for more robust information from randomised controlled trials (RCT) to inform the debate.

Some of the media reports were less cautious, but still reported the unclear picture around whether cannabis could be used medically to help people with epilepsy and whether it would be safe to do so.

The review included tentative evidence that components of cannabis may help convulsions in humans and mice, but this evidence is patchy and very weak. There were also reports of it making convulsions worse and having other negative side effects. 

Aside from the risk of bias, the evidence presented by the summary suggests that it is a compound found in cannabis that may have a protective effect against seizures, rather than cannabis itself.

The use of recreational drugs, especially stimulants such as cocaine and amphetamine, is not recommended for people living with epilepsy, as they can trigger the onset of seizures.