Epileptic seizure frequency fell by an average of 86% among 10 children treated with whole-plant medicinal cannabis, even though none of the children had responded to other conventional treatments, and some had failed to respond to a cannabidiol (CBD) product that is licensed for their condition. Findings from the case study have prompted the U.K.-based researchers to call for further exploration of the potential therapeutic benefits of whole-plant medicinal cannabis products.

Rayyan Zafar, PhD, at the Centre for Psychedelic Research and Neuropsychopharmacology, department of brain sciences, Imperial College London, and colleagues reported on their clinical study in BMJ Paediatrics Open, in a paper titled, “Medical cannabis for severe treatment-resistant epilepsy in children: a case-series of 10 patients,” in which they concluded, “This study establishes the feasibility of whole-plant medical cannabis as an effective and well-tolerated medicine for reducing seizure frequency in children suffering with intractable epilepsies.” Zafar, together with Imperial co-authors Anne Schlag, David J Nutt, and Lawrence Phillips, at the London School of Economics and Political Science, list their affiliation with DrugScience, which was founded by professor Nutt in 2010.

Whole-plant cannabis includes tetrahydrocannabinol (THC), which is the main psychoactive compound that is responsible for the characteristic “high” associated with recreational cannabis use. The plant also contains cannabidiol, other neuroactive cannabinoids, and molecules such as terpenes. Substantial anecdotal evidence as to the value of medicinal cannabis for treating childhood epilepsies has been accumulating since the 1800s, the authors wrote. However, they further explained, both recreational and medical cannabis were made illegal in the U.K. under the Misuse of Drugs Act 1971, so cannabis research largely ceased.

However, prompted by parents whose children had responded well to whole-plant medicinal cannabis extracts, but not to conventional antiepileptic drugs or purified cannabidiol (CBD oil), medicinal (whole plant) cannabis was designated a prescription medicine for the treatment of severe childhood epilepsy in 2018. “Led by parents whose children had responded well to whole-plant medical cannabis extracts but who had failed on conventional antiepileptic drugs (AEDs) and purified cannabidiol (Epidiolex), medical cannabis was re-initiated as a medicine in the British pharmacopeia in 2018,” the authors wrote.

Doctors in the U.K. have been extremely reluctant to prescribe whole-plant medicinal cannabis extracts to children with severe epilepsy, largely because of the lack of confirmatory clinical trial data, the team noted. “Despite the change in legal status of medical cannabis, most of these children have not benefited as to date there has been only three National Health Service (NHS) CBMPs [cannabis-based medicinal products] prescriptions made in total and only two in children,” the team noted. One of the reasons for resistance that is most argued by clinicians who might be prescribers, is the lack of evidence for efficacy of medical cannabis. “By this they usually mean that there are no randomized controlled trials (RCTs) that prove efficacy and without these they are not prepared to prescribe,” the authors wrote. However, they continued, it is generally accepted that RCTs are not the only way of generating evidence to the value of treatments.

The U.K.’s National Institute for Health and Clinical Excellence (NICE), which provides guidance on which treatments and therapies the health service in England should adopt, did recently put out a position statement accepting that real-world data, including case series, are valid sources of evidence, particularly where it’s difficult to carry out clinical trials—in children, for example. Zafar’s team suggested that patient case-series studies with before and after outcome measures, are, in fact “… particularly useful for conditions where RCTs are unlikely or impossible to perform in examples of rare and idiopathic conditions and especially in paediatric medicine.”

In light of NICE acceptance of case studies as valid evidence, the researchers carried out a study to evaluate the use of whole-plant medicinal cannabis in 10 children whose severe epilepsy hadn’t responded to conventional treatment, including two who hadn’t responded to the only pharmaceutical grade, purified CBD oil licensed for the condition in children (Epidyolex). The team wanted to assess the percentage change in monthly seizure frequency and the impact of medicinal cannabis on changes in conventional AED use. They also wanted to report the strengths and doses used and the costs incurred.

All the participants were recruited from two charities representing children using medicinal cannabis to treat their severe epilepsy. The children’s average age was 6 years, but ranged from 1–13 years. They had a range of epilepsies and three had other concurrent issues, including infantile spasms, learning disabilities, and global developmental delay. Data were collected from their parents or carers via phone or video conference calls between January and May 2021. All the participants received whole-plant extract cannabis-based medicinal products either through private prescription, or through the NHS. “The CBMPs used included Bedrolite (<1% THC and 9% CBD), Bedica (14% THC and <1% CBD), Celixir 20 (<1% THC and 20% CBD), Sweet Pink CBD (<1% THC and 10.6% CBD), and Althea 100 (<1% THC and 10% CBD),” the team wrote.

The children had tried an average of seven conventional epilepsy drugs. After starting to take medicinal cannabis, this fell to an average of one each, with seven of the children stopping them completely. Monthly seizure frequency reduced for all 10 children by an overall average of 86%. The researchers say that full chemical analysis of the whole-plant medicinal cannabis products used is ongoing, but they were able to assess the THC and CBD content. This showed that the children took an average of 5.15 mg THC and 171.8 mg CBD every day.

Parents and carers reported significant improvements in the health and wellbeing of their children, including in sleep, eating, behavior, and cognition after they started to take whole-plant medicinal cannabis products. “Our patient group almost universally reported highly improved cognitive and behavioral outcomes, likely due both to reduced seizure frequency and reduced use of other AEDs,” the researchers noted. They further stressed that the results “ … suggest that whole-plant medical cannabis products are superior to isolated CBD products in the patients examined.” Moreover, only a few minor side effects, such as tiredness, were reported. The average monthly cost of the medicinal cannabis products was £874. One child had obtained their prescription for free on the NHS.

The authors acknowledged limitations to their study, in that it was observational and involved a small number of participants. They also noted that the trial was retrospective and relied on parental recall, with no comparator group. So it’s possible that only those parents in whom medicinal cannabis worked well decided to take part.

The investigators further commented that additional research will be required to define the mechanisms by which the respective additive constituents of whole-plant products lead to improved clinical results. And this must include comparing the unwanted effects of whole-plant medicinal cannabis with the known harmful effects of conventional epilepsy medicines, they said. Despite the trial limitations, the researchers concluded, “Our findings are in line with several observational and controlled interventional studies that have seen significant reductions in seizure frequency following treatment with medical cannabis …”

The authors pointed out that two of the children in their sample had failed on Epidyolex. And for this reason, they said, “NICE guidance has recently been updated to clarify that this should not deter clinicians from prescribing off-license medical cannabis products such as the whole-plant cannabis medicines of which our data support for such prescribing.”

They further stated, “We believe that our data on whole-plant medical cannabis in childhood-onset severe treatment-resistant epilepsy provides evidence to support its introduction into the NHS within current NICE prescribing guidelines … Such a move would be hugely beneficial to the families, who in addition to having the psychological distress of looking after their chronically ill children, have also to cover the crippling financial burden of their medication.”