5 years on: Why the NHS still rarely prescribes medical cannabis

The NHS policy is to only prescribe medicines that have marketing authorisation. This process involves multistage clinical trials which each step allowing the drug or medicine to proceed to the next phase. Due to the nature of effectively conducting clinical research there is the unavoidable barrier of time that each phase requires. The process also involves equipment and expertise to carry out the studies in the most efficacious manner, bringing us to our next barrier to releasing a licensed medicine - the cost. Let’s take a look at the process in more detail to learn how cannabis can become a medicine on the NHS. 

What is medicine?

In the UK a medicine is defined by the Medicines and Health Regulatory Authority (MHRA) as; 

“Any substance or combination of substances which may be used in, or administered to, human beings, either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis”

The modern history of prescribing medicines in the UK dates back to 1852 when the first version of The Pharmacy Act was introduced, later reworking it in 1868 so that only pharmacists could sell the listed medicines and poisons. Later, at the start of the 20th century, international drug conventions were introduced: “The Opium Convention”. After World War 2 the UN was formed to replace the League of Nations. In 1961 they updated the Opium Convention with the Single Convention of Narcotic Drugs and member states were obliged to enact more stringent controls on the international trade of drugs and medicines. 

You can read more about the full history of UK drugs policy here. 

How does a molecule get medical recognition?

A molecule gets medical recognition through a series of tests designed to show that it works better than a placebo. Most medicines start with a pre-discovery stage, looking at the target disease and trying to learn about the physical processes taking place to learn if there is a certain receptor or protein that can be targeted. Next is the discovery stage. In synthesised medicines a selection of similar molecules will be created using cleverly designed chemical processes and test them out to see which ones show signs of activity and do not kill the subject. This process could involve screening thousands of new and existing molecules. 

Then, in the development stage the ingredients are designed to test the bioavailability with different combinations of the materials to find what works best. The tests for this could be computerised, on cells or in animals when absolutely necessary. The next stage of development is working out the most suitable delivery method which will consider a multitude of factors such as how easy is is to deliver, the potential dose size, how easy it is for the patient to administer, how much of the drug gets into the system and how long it takes to take effect or wear off. It may involve developing new technology to deliver the drug in the way that is most suitable. 

Once the groundwork has been thoroughly planned out it is time to move on to the next stage where scientists and drug developers find out if the drug they have been working on is safe and effective or if they need to go back to the drawing board. 

• Phase 1 – A small number of healthy volunteers (20-100). May take several months to collect the data. There are rare instances that a trial drug will be given to seriously ill or terminally ill patients. Tests on healthy people are easier to detect any side effects or serious reactions not caused by a complication of an existing medical condition. 

• Phase 2 – A larger group of people with the disease (100-300). May take several months to two years to collect the data. The point of this phase is to answer the question “does the drug improve the disease?” but also to discover the dose and frequency it should be administered. These trials are usually randomised so participants do not know if they are getting the experimental drug, a placebo or a standard treatment. They are also double blind so the scientists do not know which patients are in which group, further reducing any bias in treatment. The placebo and the standard treatment act as the control groups allowing researchers to answer if it works worse, as good or better than nothing or the existing medication. If it doesn’t work as well as the existing treatment it may not be a worthwhile investment proceeding and if the placebo works better then it isn’t considered effective. There is a greater chance to observe side-effects in larger study groups and with patients who have the condition being targeted.

It is important to know at this stage that only 33% of Phase 1 & 2 trials that are successful actually move on to Phase 3. Many years may pass between each phase being started due to regulatory authority, trial efficacy, planning and recruiting participants. 

• Phase 3 – Typically several thousand patients (300-2000+). May take up to 4 years to collect the data. Trials are double blind and randomised taking all of the same precautionary measures in Phase 2. Larger data sets and participant monitoring allow researchers to learn more about side effects once again and provide much of the information that gets included in the safety pamphlet inserted into each medicine box. 

The drug developer can now go to the MHRA and European Medicines Agency (EMA) request for marketing authorisation to confirm the quality, safety and efficacy of the medicine. It isn’t completely over there though, ongoing monitoring takes place for the next 20 years. 

• Phase 4 – Ongoing monitoring during the life span of the medicine. Once the drug has received marketing authorisation and can be prescribed to patients by doctors the trials continue. Selective monitoring of patients helps the drug developers to understand what the most rare side effects are, other drug contraindications and the long term user safety data that can only be collected over time. 

In the case of medical cannabis, we are considering existing molecules THC and CBD and how they can move through this process to become an authorised medicine on the NHS. As you can see, it is not as simple as saying “look, it works”. It is interesting to know that there are multiple pharmaceutical companies in the research and development stages with synthetic cannabinoids targeting specific symptoms of certain selected conditions. 

When can a medicine be prescribed by the NHS?

A medicine can be prescribed by the NHS once it has passed through a Health Technology Assessment (HTA) which reviews the cost effectiveness and clinical effectiveness who determine if they believe funding a specific drug is in the interest of the patient and the taxpayer. In the UK this is the National Institute of Health and Care Excellence (NICE), All Wales Medicines Strategy Group (AWMSG) and the Scottish Medicines Consortium (SMC). Once NICE has given a new medicine a Technology Appraisal it must be added to the NHS Formulary within 3 months. Once given a TA and on the Formulary the NHS is obliged to prescribe and source this medicine. Doctors are more likely to prescribe a medicine once it is on the NHS Formulary. 

What makes prescribing medical cannabis different to other medications?

Prescribing medical cannabis is different to other medications due to the higher level of scrutiny that prescribers are under for prescribing it. Because cannabis products have not yet passed through the standardised marketing authorisation procedure all medicines must go through, there is still an elevated level of fear and concern Currently cannabis-based medicinal products are unlicenced putting them in the “specials” category and they are often referred to as off-licence. Specials relate to their prescription under “special circumstances”. 

The Home Office has given prescribing powers to specialist doctors registered with the GMC but has so far refused to allow GPs (even private ones) to prescribe. Seeing a consultant specialist doctor through the NHS requires a referral through an NHS GP which is usually only done when it is clear there is an issue that warrants further investigation or you have failed to respond to the medicines a GP can prescribe. It’s also possible to self-refer to a private cannabis clinic where you will see the same kind of specialist consultant.

How was medical cannabis legalised in the UK?

Medical cannabis was legalised in the UK after a series of strategic campaigns by corporate and patient lobby groups who maintained a constant pressure on the government to acknowledge cannabis has medicinal benefits. Patients' stories were highlighted in newspapers with epileptic children being the ones resonating most with the public. Policing Minister and MP Nick Heard was concerned with the threat of children being used as publicity stunts in the press and consulted with patient groups, caregivers, parents and other cabinet members. These public campaigns didn’t just pull at the heartstrings, they pulled at the strings of power and the Home Secretary, Sajid Javid made the announcement in July and on November 1st 2018 the law came into effect. An amendment to the Misuse of Drugs Act 1971 rescheduling CBMP as Schedule 2 drugs means it is considered to have a high potential for abuse and potential to cause psychoactive effects. This may change over time as more evidence is published but that can only happen when more clinical trials have been undertaken and completed with a positive result. 

Is the government interested in clinical trials for medical cannabis?

Yes, the government is interested in seeing more clinical studies around THC and CBD. Contrary to popular belief (and probably due to their recorded history of opposing it) the UK government is quite welcoming of new evidence to support efficacy of cannabis-based medicinal products. 

When the Home Office announced medical cannabis was legal, the National Institute for Health Research (NIHR) created a funding program giving an opportunity for medical cannabis companies to run clinical trials where 50% of the cost would be paid by the government. This garnered some interest but ultimately failed to result in a successful partnership and was declined. Whilst companies are keen to protect their financial investments the sad side of the story lies in the fact that patients are the ones that suffer in the long run, and doctors are prevented from confidently prescribing medicines in courses they know are effective at treating the target condition. 

Are any clinical trials being conducted into medical cannabis?

Yes, there are several major clinical trials taking place looking into the efficacy of THC as a medicine for specific conditions. Jazz Pharmaceuticals are continuing GW pharmaceuticals work with cannabinoids looking into diabetes although this hasn’t seen any progress in a couple of years now. Jazz Pharmaceuticals and the Wellcome Foundation have funnelled £16.5 million into CBD research to learn if it is a beneficial medicine for schizophrenia and psychosis at Oxford University. Imperial College London are in the development stages for a double blind randomised clinical study into cannabis and acute postoperative pain, nausea and vomiting. Celadon who have a licence to grow cannabis in the UK and have just achieved marketing authorisation for the specials medicine market, have also been granted approval to run a large scale clinical trial looking into THC’s effect on chronic pain in up to 4,900 patients aged 18-85 with non-cancerous chronic pain conditions.