What did eventually persuade the government to do something was public outrage at the prospect of two young boys with epilepsy being denied cannabis oils which had previously relieved their seizures. And so, on November 1st 2018, the UK Home Secretary Sajid Javid took the decision to reschedule cannabis from a Schedule 1 drug to a Schedule 2 drug, thus allowing certain cannabis-based products for medicinal use (CBPMs) to be prescribed. As we approach two years since this event, it’s worth pausing to reflect on progress in getting access to this medicine, which for some patients has proved to be life-changing. Estimates suggest that around 1.4M people in the UK continue to use illicit cannabis for medical purposes, while only c. 2000 legal prescriptions have been issued in the two years since legalisation.
Meanwhile, Germany has an established medical cannabis market treating 100,000 patients suffering from conditions like chronic pain. In North America, cannabis has been deemed an essential service during lockdown and sales have boomed. So why are things so slow in the UK?
Let’s start by listening to patients
My personal journey over the last 5 years has taken me on a tour of global cannabis, learning about the different perspectives that different parts of the world have on this plant. Cannabis is on a journey from drug to medicine to lifestyle and it’s helpful to understand the range of views. The conversation around cannabis in much of North America – where recreational cannabis has been legal for the past 5 years in Colorado and 2 years in California, Nevada, Massachusetts and Canada – is focused on lifestyle brands and economic benefits such as tax receipts and job creation. “Medical Marijuana” is a thriving market now legal in 35 US states, giving 95% of Americans access to some form of cannabis. However, this sits outside the regulatory purview of the FDA – self-medication is the model for cannabis in the US.
In Europe, we are firmly on the path from cannabis as drug to cannabis as medicine; cannabis has been legalised for medical purposes in 22 countries, and a €250M European market has been established over the past 3 years. Things are moving in the right direction, but not nearly quickly enough to improve the quality of life of many millions of patients who need access to this medicine. Unlike in the US, European medical cannabis provision is regulated by government healthcare agencies. These agencies expect to see the same high quality evidence for cannabis that they see for other medicines. The double-blind, placebo controlled Randomised Control Trial is viewed as the gold standard of evidence by European healthcare systems, and until medical cannabis has data from that kind of clinical study, there will always be sceptics. However, what does exist is a wealth of anecdotal data and observational studies. The testimony of patients around the world finding therapeutic benefit from medical cannabis is entirely valid in the context of their own lived experience, but challenging to integrate into the existing RCT framework for assessing drug safety and efficacy.
The notion of the patient’s own lived experience being at odds with the views of the medical establishment has proved to be an issue that transcends medical cannabis. Our health system is undoubtedly full of people who are doing their best to help patients. But over time, a combination of a focus on efficiency and a disregard for the voice of the patient – in particular when listening to the voices of women and ethnic minorities – has left us with a healthcare system that is ripe for reform. Earlier this year, The Independent Medicines and Medical Devices Safety Review published the results of a two year investigation into patient testimony on vaginal mesh, hormone pregnancy tests such as Primodos, and sodium valproate (a drug for epilepsy). Patients and their families had continually raised concerns about the safety of these treatments but unfortunately their voices were not heard until it was too late. As Baroness Cumberlege, author of the report says:
“We have found that the healthcare system – in which I include the NHS, private providers, the regulators and professional bodies, pharmaceutical and device manufacturers, and policymakers – is disjointed, siloed, unresponsive and defensive.
It does not adequately recognise that patients are its raison d’etre. It has failed to listen to their concerns and when, belatedly, it has decided to act it has too often moved glacially.
Indeed, over these two years we have found ourselves in the position of recommending, encouraging and urging the system to take action that should have been taken long ago.”
The MHRA response to the report was an acknowledgement of the need for change:
“Throughout the Review’s work we have listened intently to the many distressing experiences of women and their families… We are therefore making changes without delay to ensure that we listen to patients and involve them in every aspect of our work.”
Medical cannabis has transformed the quality of life for many patients and families who have exhausted traditional pharmaceuticals. It’s time we listened. Cannabis is a treasure chest of therapeutic molecules (cannabinoids, terpenes, flavonoids and more) and offers many combinations of medicines for the body. Medical cannabis is frequently used for the management of long-term symptoms and the patient has to actively engage in understanding their own body and mind in order to iterate to the most effective treatment for a particular symptom at a particular time. This is not an experience that is necessarily suited to a well-defined clinical endpoint in a RCT, but rather a desired patient state.
There are also economic reasons for the lack of research supporting cannabis, and again, the issues in cannabis mirror broader structural challenges in healthcare. The US pharmaceutical industry accounts for in excess of $1 trillion in economic output each year, yet there are still no approved therapies for 95% of human diseases – conditions impacting billions of people. Many medicines and vaccines have immense potential benefit to society, but are challenging to capture commercial value from. The average cost to bring a licensed brand name drug to market is $1.3B and drug companies earn a return on this huge investment over a period of market exclusivity of up to 20 years. Once this period of exclusivity is over, prices drop as generics manufacturers slash the cost of production. In fact the average cost of a brand-name drug was 18.6 times higher than its generic equivalent in 2017, and the size of that gap has more than tripled since 2013.
There is insufficient profit potential for most companies to develop therapies for rare diseases, or for diseases which affect the global poor. It is difficult to incentivise companies to put R&D dollars into repurposing generic drugs for different conditions. And it is extremely challenging to make the profit margins of a licensed pharmaceutical from a naturally occurring plant like cannabis.
This lack of commercial model may partly explain why traditional pharmaceutical companies have not focused R&D resources on cannabis. Amongst calls from government and regulators for RCT evidence, the question of how businesses are to rationalise funding the development costs of a brand name drug while only being promised the potential payoff profile of a generic drug has not been addressed. GW Pharmaceuticals, the leader in cannabinoid medicines, has approached this problem by focusing on rare diseases which offer regulatory exclusivity (e.g. Lennox-Gastault, Dravets, Tuberous Sclerosis), tying up IP for future indications and aggressively defending their patent portfolio.
Cannabis medicines today sit uneasily in the doctor’s cabinet: rarely prescribed on the NHS; poorly understood in the private sector; widely used in the illicit market. The continued lack of product availability and clinical education leads to frustration for patients. Doctors understandably shy away from medical cannabis products which are still not wholly accepted – the feeling remains that rescheduling was imposed by politicians rather than introduced through the generation of high quality evidence. Regulators and pharmaceutical companies naturally tend towards isolated, synthetic molecules which fit the RCT framework, but which do not account for the synergistic effects that are theorised for cannabis. In summary, it’s an unacceptable situation and patients are enduring great suffering while standard treatments fail to alleviate their symptoms or actually make them feel worse.
The path forwards
Prior to the pandemic, we already knew that an ageing society suffering from chronic conditions was going to place an unsustainable burden on our healthcare system. The pandemic has brutally exposed the fragility and inadequacy of our health and social care provision. We are rethinking how we take care of ourselves holistically – body, mind and soul – and one of the impacts of the pandemic is a broad move towards wellness. People are being proactive – food, exercise, sleep choices are different, and we are spending time in nature or on creative pursuits, thinking more deeply about community and connection. Preventative medicine is the focus.
We also know that the Endocannabinoid System – the master regulator of body and mind – has a critical role to play in this pursuit of wellness. Over time, more academics, researchers and scientists will also learn about how cannabinoids play a restorative role in the body. Gradually more pieces of the jigsaw puzzle will emerge, and eventually we strongly believe we will demonstrate that cannabis medicines are safe and effective. The events of the last few months have laid the ground for a fundamental reassessment of cannabis and its role in healthcare.
Some progressive European countries (e.g. France, Denmark, Germany) are collecting Real World Data and Real World Evidence on medical cannabis from registries. A patient registry is “an organised system that uses observational methods to collect uniformed data (clinical and other) to evaluate specific outcomes for a population defined by a particular disease, condition or exposure and that serves a predetermined scientific, clinical or policy purpose”. This data will help clinicians and regulators evaluate whether cannabis is safe and effective. Here in the UK, Project Twenty21 is a registry for medical cannabis which was established by UK charity Drug Science and has the support of a number of industry partners including Alta Flora. The study is coming up on its first anniversary and is collecting registry data which we hope will contribute to medical cannabis eventually being prescribed on the NHS.
Measure what matters
In our early conversations with patients, it was clear that recording data on how they consumed cannabis and the effect on symptoms was critical to manage their conditions. Paper-based logs to record the strain, dose and time of medication were common in order to develop an understanding of what worked best for different symptoms – cannabinoid ratios, terpene profiles, cannabis phenotypes. Some patients were consuming cannabis oil and flowers concurrently. The most sophisticated were logging what they were eating, how many hours they were sleeping, and in some cases daily steps taken. Furthermore, patients who had captured this data found that they were taken more seriously by their doctors. Rather than finding their clinicians “unresponsive and defensive” as Baroness Cumberlege described, patients were educating and engaging their doctors with data about their lived experience.
We decided to build tools to bridge the divide between patient and clinician, and to help industry solve the economic and scientific issues impeding cannabis. We have built a data service: Eva means “Giver of life” and is a tool for patients to measure what matters to them – symptoms, medication and health outcomes – in order to live better. We have tried to build Eva with empathy for the patient and an understanding of the needs of the healthcare system.
We are grateful for input and expertise from beyond our own team as we build Eva. We work closely with academics at King’s, Imperial and UCL and liaise with many patient groups. We engage actively with regulators both in the UK and in Europe and have started conversations with Licensed Producers and Clinics who are interested in using Eva to support their offering to patients.
We launch on Android with the EuroQol EQ-5D Quality of Life questionnaire (used by NICE for QALY benchmarking), and we will over time add other validated scales and questionnaires which are tailored to the condition that the patient has. With the focus on data comes a series of questions around T&Cs, privacy, confidentiality, security, ownership, and regulations. We think ‘privacy by design’ and Eva is GDPR compliant. We commit to transparency around the use of healthcare data with independent scrutiny of our data practices. We are sharing more on our philosophy, policies and practical use cases of the data on our blog later this week.
The Patient-Generated Health Data (PGHD) which Eva captures offers academics, researchers, manufacturers and clinics an opportunity to undertake an entirely new kind of research. We hope to soon be able to collect real-time data on a patient’s cannabinoid consumption, changes in symptoms, subjective Patient Reported Outcome Measures (PROMs) via academically-validated scales, and objective digital and wellness biomarkers.
We are exploring taking Eva beyond cannabis into other areas which are stigmatised, complex and where there are unmet needs for patients who are not being heard or seen. Psychedelic-Assisted Psychotherapy is an area of medicine which shows huge promise with a range of mental health conditions. Alta Flora is a member of the Drug Science Medical Psychedelics Working Group which was established to create a rational and enlightened approach to psychedelic research and clinical treatment; we hope to play in building that approach with Eva. There are further applications in pharmaceuticals, longevity and wellness more broadly which we are also excited to explore; I believe that there is potential to use Eva to gather data on the use of cannabis / CBD with COVID symptoms – something which could add to the evidence base on the virus.
We are now opening up access to Eva in the UK and will be taking feedback from patients to learn about how we can improve the service. Our iOS app will be out in early December.
On a final personal note, there are too many people to thank who have played a role over the past 5 years but I’m extremely grateful to my team who are among the most resilient, passionate and committed people I’ve met.
Eva can be found here and we are excited to get going.