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Cannabis on trial

How will the NHS conduct accurate trials of cannabis-based medicinal products when everyone has already tried cannabis? Dr David Horn, medical director at the Centre for Medicinal Cannabis, reports.

Until November 2018, cannabis was a Schedule 1 drug under the Misuse of Drugs Regulations 2001. This schedule defines its contents as “considered by the government to have no medicinal value.” Thus the medicinal properties of cannabis were overlooked by the NHS. Cannabis related substances, bar a couple of MHRA licensed drugs, therefore exempted from Schedule 1 but ascribed low clinical priority by NICE, were summarily ignored for medical use.

As Dame Sally Davies has testified to the Health Select Committee, following her review of reviews upon which the home secretary has relied, cannabidiol (CBD) is adequately proven to be of clinical use in Dravet’s and Lennox-Gastaut epilepsy syndromes. The status of CBD has always been outside of the Misuse of Drugs legislation, due to the fact it is not intoxicating.

CBD is classed as a novel food – it was permitted as a foodstuff by EFSA provided that the THC content was less than 0.2%. However, in January, EFSA updated its novel foods catalogue, and a food safety assessment is now required unless there is a successful objection to this change. However, products containing the ingredient can be found on shop shelves throughout the UK. What has turned things around in the medical establishment is relatively recent observational trial data.

Poorly controlled epilepsy occurs in approximately 20% of epilepsy in children, and is defined by resistance to treatment with at least two first line drugs, ketogenic diet and surgery where appropriate. Children may experience tens or even hundreds of fits per day, potentially an existential threat.

Cannabis-based medicinal products (CBMPs) with a 20:1 ratio of CBD to THC are shown in Israeli observational trials to be effective in treating 50% of these patients, who will experience 50% less fits. A further 25% will experience 75% cessation and 4% will have no fits at all. Given the THC level falls under the Misuse legislation, regulators have wisely now, by way of its rescheduling, stepped back to empower the medical establishment to deal with the situation, with a generous NIHR grant programme also being ordained.

Respite for UK medicine is granted due to the fact these open label observational trials (that tend commonly to exaggerate efficacy) demonstrate a signal, but do not of themselves turn data into knowledge. Though with pressure mounting to deal with the fallout of change in political stance towards cannabis (medicinal and recreational), the time has now come for randomised controlled trials – and the BPNA have these in current conception.

Nevertheless, public, political and medical attitudes towards the drug are evolving fast, and it seems we are late to the cannabis party. In a world of internet-enabled patients, medical tourism, and the threat of legalisation for recreational use spreading eastward across the Atlantic (driven by growing political necessity), time is short.

Already, impatient UK parents such as those of Teagan Appleby are travelling to the Netherlands to legally seek cannabis treatment for epilepsy, as many others already do from Germany. It is worth pointing out that it is potentially not in the interests of UK patients because they are likely to be excluded from any imminent UK trials on the basis of a requirement to remove the “signal noise” borne of pre-existing exposure. GPs might therefore advise parents appropriately against medical tourism, and well-meaning Patient Advocacy Groups might consider how they will support their now excluded patients who could remain so for many years as a result of their intervention. Given the developmental question hanging over THC, this is not likely to be resolved for an extended period.

However, a greater threat arises from recreational use. Recreational cannabis is far cheaper to produce and for the public to source than medical grade. This a substantial medical risk to patients due to the uncontrolled nature of production, exposure to dangerous contaminants such as heavy metals, aflatoxin, moulds, pesticides, and highly-variable batch cannabinoid content. As Canada is now finding out, it is extremely difficult to undertake clinical research now that there is wide access to CBMPs. Potentially every trial participant has already used cannabis.

Unless there is rapid expansion in UK cannabis research, patients who feel they could benefit from medicinal cannabis may well lose patience and take the matter into their own hands for issues of chronic pain, fibromyalgia, allodynia, insomnia, and anxiety. Patients are already “growing their own” and campaigning to be able to cultivate their cannabis due to the frustration they have at not being able to access CBMPs via the NHS – despite them being legal for six months.

Like Canada, the UK would find it equally difficult to conduct classical sense medical trials in this scenario. Without adequate trials, justification for NHS prescription of safe medical grade CBMPs may never become publicly funded. This could usher in deregulation as the only cost-viable alternative in the face of uncontrollable public demand. Alternatively, by rapidly responding to this research challenge now, before it is too late, the UK might well become uncontested leaders in this field with safe, affordable medical cannabis available upon NHS prescription.