Back in October, it was announced that the NHS would be, at long last, backing clinical trials into medical cannabis. The trials, which will aim to investigate the safety and effectiveness of CBD and THC in adults and children with epilepsy, are due to start in 2025. But while this might sound like good news on the surface, there has been an ongoing debate among many experts and advocates around the suitability of these trials.
So, what are the plans for these NHS-backed clinical trials? And why are some people unhappy with them?
A quick recap
The UK government legalised cannabis-based medicines in November 2018, following the high-profile cases of two children with severe, treatment-resistant epilepsy. Since the law change, specialist doctors have been able to prescribe medical cannabis for a wide range of conditions; however, NHS access to these medicines has remained extremely limited, prompting widespread criticism from patients and advocates.
A lack of clinical evidence and limited recommendations from the National Institute of Health and Care Excellence (NICE) are often cited as the reason NHS clinicians are unwilling to prescribe medical cannabis. According to NICE’s recommendations, cannabis-based medicines should only be considered in the treatment of spasticity associated with multiple sclerosis, chemotherapy-induced nausea and vomiting, and rare forms of treatment-resistant epilepsy – and even then only as a last resort.
The long-awaited clinical trials
In October, it was announced that two national NHS-backed clinical trials would be conducted to investigate the potential of cannabis-based medicines for early-onset and generalised, treatment-resistant epilepsies. The trials will be led by researchers at the University College London (UCL) and Great Ormond Street Hospital for Children NHS Foundation (GOSH). They will be funded by a partnership between NHS England and the National Institute for Health and Care Research (NIHR).
A reported 500 adults and children will be enrolled in the trials, during which they will be randomly assigned formulations of CBD, CBD with a small amount of THC, or a placebo. In addition to assessing the safety and effectiveness of medical cannabis for reducing seizures, the trials will also investigate how they affect sleep, learning, behaviour, mood, and quality of life in these patients.
The trials were first proposed back in 2019 and such a lengthy delay has only added to the criticism of the state of medical cannabis access in the UK. But that’s not the only source of discontent in relation to the trials. Let’s take a closer look at what is being said about the trials.
An unsuitable trial design?
Randomised controlled trials (RCTs) are widely considered to be the gold standard in medical research. They involve randomly assigning groups of similar people to two or more drugs to compare their effects. However, many experts point out that this kind of research is often not suitable for assessing medical cannabis products.
As Professor Mike Barnes, a consultant neurologist and medical cannabis expert and prescriber, has long pointed out, randomised controlled trials are “fine for a new single-molecule pharmaceutical product but doesn’t lend itself to the cannabis plant which is a complex organism.”
Hannah Deacon, a prominent campaigner whose son, Alfie Dingley, played a key role in the 2018 law change, reiterated this alongside Prof. Barnes in a recent LinkedIn post criticising the trials: “If we continue to follow the same RCT route we ignore the compounds of the plant and rare disease. My son is one of nine boys with his rare condition, if we only use the RCT model we ignore him and many patients like him.”
Another key point mentioned by Ms Deacon in the accompanying video is that participants in the study must go through an 8-week wash-out period, during which they will not be able to take any cannabinoid-based medicines. As many patients with treatment-resistant epilepsy face potentially life-threatening seizures, this could prove dangerous.
Alongside Varinder Kaur, Professor Mike Barnes and Hannah Deacon recently co-wrote – a resource for healthcare professionals, patients, and regulators titled the Medical Cannabis & Epilepsy. It includes a review of over 100 clinical trials, real-world studies, and observational research on the role of medical cannabis in epilepsy management.
The wrong formulations?
Indeed, cannabis is a complex plant containing thousands of active compounds. Perhaps the most prominent of these compounds are cannabinoids and terpenes – a huge number of which have been found to possess therapeutic potential. Moreover, these compounds are often believed to work together to produce many of the benefits of medical cannabis – a phenomenon known as the ‘entourage effect’.
This is the root of further criticism into the trials: that they will only assess cannabinoid isolates. That isn’t to say isolated cannabinoids can’t be effective. After all, Epidyolex – the only cannabis-based medicine so far licensed for the treatment of epilepsy – is a CBD isolate formulation.
However, as Prof. Mike Barnes points out in the clip above, many patients who are privately prescribed medical cannabis to treat epilepsy are receiving full-spectrum products, often following a lengthy process of identifying the optimum formulation.
Experts and patient advocates have long argued that medical cannabis is not a one-size-fits-all treatment and a more tailored approach is needed. And many epilepsy campaigners agree. In a post published in April, the Epilepsy Research Institute UK point out the need to “develop and test therapies which are tailored for individuals and ultimately help more people live a life free from epilepsy.”
On the bright side…
The response to the trials hasn’t all been critical. Indeed, the fulfilment of a five-year promise to initiate these clinical trials is, broadly speaking, is good news. A prominent voice coming out in defense of the trials in recent weeks is that of Charlotte Caldwell. As the mother of Billy Caldwell, one of the children who prompted the 2018 legalisation of cannabis, Ms Caldwell has become a prominent campaigner for medical cannabis access in the UK.
In a LinkedIn post in October, Ms Caldwell described the announcement of the trials as “Fantastic news”. She notes that “the trials, if successful, that no other child suffering with refractory epilepsy will have to endure the long and tortuous journey that Billy did to receive life saving treatment on the NHS.”
And many people appear to agree with her. But the emphasis remains on “if” the trials are successful.
The bigger picture
Of course, the commencement of these clinical trials is taking place within a much broader context. A context in which some parents are still paying up to £2,000 every month to fund medical cannabis treatment for their children with severe epilepsy.
One thing that everyone seems to agree on is that, six years after legalisation, this shouldn’t be the case.
Some put these high costs down to the need for complex extraction processes in the manufacture of medical cannabis oils; however, there are growing calls for more transparency in the industry and, ultimately, a reduction in these costs.
The question is whether the recently announced clinical trials will help to improve this state of affairs. But with the trials set to take place over four years, it could be a long time before we find out. In the meantime, it is likely that access to medical cannabis will remain largely reliant on private clinics. And even if they are successful, existing patients who are prescribed full-spectrum products are unlikely to benefit from NHS prescriptions.
Only time will tell
Since the announcement of these clinical trials, many have speculated that the proposed design and formulations are unlikely to yield positive results. If this happens, there is concern that the trials will do the opposite of what is hoped. Rather than helping to progress access to medical cannabis, the credibility of medical cannabis therapy could be compromised in the eyes of would-be prescribers and the public.
Could it be, as Prof. Barnes puts it, that these trials have “been designed by people who, frankly, don’t really know what they’re doing”? Or is some degree of research simply better than none?
