Health and Social Care Committee
Oral evidence: Drugs policy: medicinal cannabis, HC 1821
Tuesday 19 March 2019
Ordered by the House of Commons to be published on 19 March 2019.
Members present: Dr Sarah Wollaston (Chair); Mr Ben Bradshaw; Johnny Mercer; Derek Thomas; Martin Vickers; Dr Philippa Whitford; Dr Paul Williams.
Questions 1 - 133
Witnesses
I: Professor Dame Sally Davies, Chief Medical Officer for England, Department of Health and Social Care; and Alette Addison, Head of Pharmacy Development and Regulation, Department of Health and Social Care.
II: Genevieve Edwards, Director of External Affairs, MS Society; Professor Mike Barnes, Interim Chair, Medical Cannabis Clinicians’ Society; and Peter Carroll, Campaign Director, End Our Pain.
III: Professor Helen Cross, Head of Development Neurosciences, UCL GOS Institute of Child Health; Dr Imran Malik, Committee member, Royal College of Psychiatrists; and Professor Sanjay Sisodiya, Chair of the ABN Epilepsy Advisory Group, Association of British Neurologists.
Written evidence from witnesses:
- Department of Health and Social Care
- Royal College of Psychiatrists
- Association of British Neurologists
Witnesses: Professor Dame Sally Davies and Alette Addison.
Q1 Chair: Welcome to the Select Committee for our inquiry into medical cannabis. To set the scene for those following from outside this room, on 1 November 2018 regulations came into force to reschedule cannabis‑derived medicinal products to schedule 2 of the Misuse of Drugs Regulations 2001 and to allow prescribing of these products, but only by a doctor who is on the GMC’s specialist register. It is widely acknowledged that expectations were raised, both for families who have children living with very severe forms of epilepsy and for a number of other conditions. In our hearing today, we would like to explore some of the wider issues that lie behind that decision and how well the current regulations are working.
Welcome to our first panel. Professor Dame Sally Davies, you are very well known to this Committee and to many people following from outside. Would you like to start by introducing your role, and then Alette Addison? That would be great.
Professor Dame Sally Davies: Thank you. I am the chief medical officer for England and the senior medical adviser to the UK Government. By background, I was a haematologist. I then went into the Department to run research and set up the National Institute for Health Research—NIHR—so I am a clinical researcher and fellow of the Royal Society. From that I graduated, you could call it, to become the CMO. I am now pretty expert at public health, and my role in this comes not only from concern about patients and the public getting the best treatment but because I was asked by the Home Secretary and the Secretary of State for Health to review the scheduling of cannabis for medicinal use.
Alette Addison: My name is Alette Addison. I work for the medicine and pharmacy division of the Department of Health and Social Care, and I have been working on cannabis policy for the last five months.
Q2 Chair: Thank you. Professor Davies, could you set out what you think the current evidence base tells us about the efficacy and safety of cannabis‑derived medicinal products?
Professor Dame Sally Davies: In my report, published on 3 July, I laid out that I had done a review of reviews, particularly by the National Academy of Sciences in the States, which had done a very good review—I declare that I am an elected member of that—and by the regulators in Ireland and Australia, and one other. What was the other review? There were four of them. Maybe there were three.
It was clear to me that there is some evidence, though contested, as no doubt we will discuss, that there can be clinical benefit from cannabis‑related medicinal products, or cannabis medicinal products. Because cannabis medicinal products at that stage were schedule 1, which meant it was illegal to use them in any form, we were not able to do research and therefore improve the evidence base. In fact I have thought this for some years, when I was in charge of funding research. It was quite clear that there was evidence that they may well help a number of patients. Therefore, I recommended moving them from schedule 1—the family—to schedule 2, where they remain controlled.
As we will no doubt discuss, these drugs are not licensed, outwith a couple for very limited areas, but that then allows us to prescribe them as controlled drugs at a doctor’s choice, following guidance, and, most importantly, to get the evidence base. Without an evidence base, we are stuck: we cannot license the drugs and move them into whatever turns out to be their rightful place in medicine.
Because we are going to be short of time, I should say that it goes in various phases. You find a drug, you test it and produce an evidence base that will do for licensing, but then in this country, following licensing, which shows that it has effectiveness and safety—I have concerns about the safety—you have to move to a NICE evaluation to see whether it is cost‑effective. One of the drugs that is available at the moment and licensed for multiple sclerosis did not pass the NICE cost‑effectiveness threshold. We have various stages to go through, but I was very keen, and recommended, that we should start to progress that, so that we get the best outcome for patients as soon as we can.
Q3 Chair: With your hat on of experience of having set up the NIHR, how do you propose to make sure that we can get sufficient and appropriate trials off the ground as soon as possible?
Professor Dame Sally Davies: At the same time as launching my report, the Department announced that NIHR was launching a call for research, randomised controlled trials, to develop the evidence base. The first call finishes around now and there is a second call that will finish at the end of July. I think we have a role for the public sector to fund these studies because they matter to patients, but for any other drug we would expect the manufacturers who are going to make the profit at the end of the day to fund the licensing trials. That is what is needed. Randomised controlled trials are the only way to get these drugs licensed and they would normally be funded by the industry. It is time that the industry started to say what they are going to do about funding trials to get the licences so that patients can have access. This cannot be just left to the public sector.
Q4 Dr Whitford: What would you say is the most pressing gap in the evidence that is required?
Professor Dame Sally Davies: We have opened a Pandora’s box, and there is a belief that it works for many conditions. There are over 100 chemicals in cannabis. We are generally talking about cannabidiol—CBD—but sometimes we are talking about THC. The work to date, as I understand it, suggests that cannabidiol is pretty safe, and Sativex for multiple sclerosis is cannabidiol pure.
The first problem or issue is: does that work in all those other areas, like epilepsy? There is some evidence that it probably does for some patients. Some preclinical work suggests, though, that in some animals it might be proconvulsive and cause more convulsions. Meanwhile, what is the impact of taking it for a prolonged period of time? THC has an impact on the brain; it causes depression, schizophrenia and brain development problems in the young and adolescents. If a pregnant mother were taking it, I would be very worried. We need more data on that.
If we can get a licence, which I expect we will if enough research is done, you are into the balance not of whether it works and is generally safe and the cost, but for an individual patient, which is what we are all talking about, of whether it can help the patient and what is the likely harm. Monitoring and balancing of that is what we as doctors do all the time, of course.
Q5 Dr Whitford: In your review of reviews, were there particular areas? The most acute in talking to families is obviously children with intractable epilepsy. What was the evidence like when you were reviewing the reviews in other countries? Did you feel that that area stood out, or did you not find sufficient evidence?
Professor Dame Sally Davies: It stands out that the National Academy of Medicine did not think the evidence was strong enough to prescribe it for intractable epilepsy, whereas the Australian and Irish studies thought there was an evidence base. That is why it is so disputed. People who have really looked at all the primary studies cannot agree. That is why we need more evidence.
Q6 Dr Whitford: What do you think are the particular barriers? Obviously, we hear from families about the issue of accessing it. Do you think, particularly with regards to children with uncontrolled epilepsy, that there would be an advantage in perhaps developing a few centres across the UK where that expertise could be developed quickly, and where the children being brought forward were, at the very least, part of observational studies? They should all be on the gold standard of traditional treatment already; if their epilepsy is that bad, I imagine that they are on everything at the moment.
Professor Dame Sally Davies: I have always thought it was an advantage, if you have a very difficult-to-handle disease, to go to specialised centres that know what they are doing, and I hope that no one at this stage is offered treatment with a cannabis‑related medicinal product unless it is a last resort. I absolutely understand where the parents are whose children have responded, and those who have not found access available as yet, but my concern with an observational study is that that delays the licensing at the end of the day, because observational studies do not give you strong enough evidence to move you through to licensing; we need randomised controlled trials. It is a short‑term fix but gives us a much longer problem. We need to find ways to work with this group of patients, who have such distressing lives, to do the research that will move the whole field forward as fast as possible.
Q7 Dr Whitford: Looking at the breast cancer trials I was involved in when I was still working as a surgeon, obviously depending on the endpoints, even a randomised controlled trial can be broken if the difference is so dramatic between the two groups, which is obviously the experience that families are reporting, but at the moment the numbers are tiny. Would it not be a possibility for the most urgent cases that it is a randomised controlled trial, but the outcomes aimed for measuring actually allow that, and they set levels that allow interim assessment, and so on?
Professor Dame Sally Davies: I am absolutely with you. Modern, good trials have a blinded data management committee who regularly review the data, and if it is clear that it is harmful, or that it is an advantage, you break it and you stop there, and then you, of course, ethically provide the drug to the rest of the people who were in the trial and not taking it. I would think that was the right way to do the trial and the best way to get to the right answer. Then we can progress to licensing. Whether it will come in at a cost that the NHS is prepared to pay is a separate issue, but in general, when patients are started on a drug through a trial, it is considered ethical to continue it for those individuals.
Q8 Dr Whitford: One of the problems is licensing, and the issue of doctors prescribing unlicensed drugs and the personal financial risk they have to take. I have signed the form many times myself and it has very scary wording. Surely, regardless of getting through the NICE process, getting it licensed would be the key step.
Professor Dame Sally Davies: That is what I want, which is why I think randomised controlled trials properly done are the way to go forward. It would be great if the industry would make a contribution to that. They may have very different drugs, but these days we have, as you know, methodologies with basket trials and things where you can put in different drugs. Maybe they cannot pay that much, but they could lodge in a trust some of their shares, so that, if it comes to make a profit out of our NHS, we can plough that back into better care. There have to be ways through this that will help patients to get things that work.
Q9 Dr Whitford: Do you want to add anything, Alette, particularly about the idea of perhaps the Department pushing almost the establishment of a few centres of real expertise to carry out the trials?
Alette Addison: The law has made it the responsibility of specialists to prescribe, so we already have in place a mechanism by which the people who are the most qualified to prescribe do so. They network and discuss cases already, so there is that sort of building of expertise as we go through. We are very early in cannabis policy, and that expertise can only grow.
Q10 Dr Williams: Sally Davies, you said there are some concerns about the effect on the brain of cannabis‑derived medicinal products and that we should wait for randomised controlled trials. The difficulty that people listening will feel about that is that, if you are the parent of a child with intractable epilepsy, you are equally, perhaps even more, concerned about the effect on your child’s brain of having intractable epilepsy and multiple seizures. Also, they are not in a cold, sterile clinical environment; they are living in an environment where they have heard that there is something that might make a difference. They are seeing harm and there is something that might show a benefit. Is an RCT the right and only possible methodology to establish efficacy and safety?
Professor Dame Sally Davies: I absolutely understand what you are saying. I started life as a paediatrician and I looked after some children with pretty horrible epilepsy, although I do not believe there was anything as bad as we now see in this particular situation. Of course, lots of fits can damage the brain, so it is always a balance. But there is that bit of preclinical work that suggests that in some animals it can be proconvulsive. You have to balance all of this.
The only way we can get it licensed is through doing randomised controlled trials. My belief is that we need to get on and do that as fast as we can, with modern technologies and checking where we are all the time through a blinded data management committee, so that we break it as soon as it is proved one way or the other. Without that, what we will do is just dish it out, if the doctors will. It is very difficult, and we will not get an answer.
Alette Addison: It is important to note that we have a medicine coming through the licensing system; it has already been licensed by the FDA and it is going through the European Medicines Agency. A CBD pure oil, an extract of cannabis—Epidiolex—is being made available. It has been made available to over 80 patients on the NHS already. Our difficulty is that the evidence for adding THC to CBD, and whether that actually makes any difference whatsoever, does not exist at the moment and that is what we need the trials for.
Q11 Dr Williams: Have you been surprised by the small number of prescriptions that have been issued so far for cannabis‑derived products?
Alette Addison: No. When we look at the experience of other countries that have legalised, it is a very slow start and it builds. Even in Canada, where it has been available for 10 years, there is still only a reasonably small number of physicians who prescribe. The other thing we need to bear in mind is the evidence base. Doctors will only be confident prescribing, signing the form, if they have the evidence base to do so. It is not there at the moment.
Q12 Dr Williams: The other factor is that doctors are more confident if they have guidance. Do you think that the current guidance is perhaps too restrictive?
Alette Addison: The current guidance reflects the best international evidence available; it is absolutely congruent with the evidence and the advice that has been provided to clinicians in Australia, Canada and across the world, because it is based on the best international evidence available. We have commissioned NICE to do their clinical guidance. They have a world‑renowned way of developing that guidance, and we expect it to be published in October this year.
Q13 Dr Williams: Would you be of the view that there is a need for more clarification of guidance at the moment, more education for practitioners?
Professor Dame Sally Davies: We need doctors to get used to the idea of prescribing cannabis, but it will always, until we have a licence, be at their own risk as a non‑licensed medicine. It is right that the expert doctors provide the guidance, but, because we have NICE, I have in fact written to NICE and on behalf of the health system commissioned them to look at this carefully. They are used to weighing up all these things and it is their role to provide the definitive guidance. We have also commissioned Health Education England to do some e‑learning for doctors in general.
To go back to where I came into this, which was, “Were the cannabis‑related medicines in the right place on the schedule?”, they were in the wrong place. There is some evidence that they can help and I want to make sure that we sort that through and get licensed medicines, if they are safe and work, so that patients can get them. We are going along on that journey, but it is never a fast journey. The Government have been quite expeditious actually.
Q14 Dr Williams: What points and guidance have you particularly asked NICE to address?
Professor Dame Sally Davies: They consulted, so they are going to look not only at epilepsy but at pain, nausea and vomiting, particularly associated with chemotherapy, and again at multiple sclerosis, as I remember it. They have consulted and people came forward.
Q15 Dr Williams: When will the guidance be available?
Professor Dame Sally Davies: It is scheduled for October.
Q16 Dr Williams: We have taken some evidence that there is going to be a group issuing some alternative guidance tomorrow. Are you aware of that and what are your thoughts on it?
Professor Dame Sally Davies: No. Who would they be?
Q17 Dr Williams: It is the all‑party parliamentary group—we have taken evidence from them—together with a campaign organisation, I believe.
Professor Dame Sally Davies: I know that they want to help patients, just as we do, so I welcome their help on behalf of patients, but of course it will have no legal standing, which NICE does. We will have to see what doctors do, because we cannot persuade doctors to follow guidance that has not come from their own specialist associations and NICE. I am hopeful that it will help.
Q18 Chair: Can I ask a question on behalf of some of the witnesses, people who have given evidence to our inquiry? They make the point that, for children living with very severe forms of epilepsy, some of the medicines that they are already being prescribed have not necessarily been through those kinds of processes in the same rigorous way, and themselves have some very serious side‑effects. Are we applying a higher bar to cannabis than might have been applied in the past to some of the existing therapies?
Professor Dame Sally Davies: You would have to ask a neurologist what else they are being prescribed, but I would say that the bar is set at the level we should be setting for non‑licensed medicines. When you consider that we have just had an Act of Parliament to change the scheduling, the fact that we are treating them just as any other unlicensed medicine is quite a good move.
Q19 Chair: Yes. Could you perhaps give us some examples where in the past there has been, anecdotally, pressure to go down a route for a treatment that turned out in the long run to be rather disastrous?
Professor Dame Sally Davies: I am about to give a lecture on this, so I have been looking it all up. The one I remember with great clarity, because I will have caused suffering and maybe death, as many doctors of my generation will have done, is steroids for head trauma. When I graduated, we knew the animal evidence was that, if you had brain swelling and you gave steroids, it made it go down and things went better. We know that, if you have brain swelling—oedema—with cancers and you give steroids, it goes away.
We all gave steroids to head trauma patients, and there were rather more of them because there were more traffic accidents because there were no seatbelts. Then someone came along in the early 1980s and said there is equipoise and managed to persuade people to do the randomised controlled clinical trial, and the outcomes are worse if you give steroids. People then looked at the cause of the oedema, and of course there is a quite different cause of the brain swelling—the oedema. If they had looked at it decades before, we would have known that. That is an example of how anecdote drove a treatment that someone queried, the RCT was done and we all had to change behaviour.
To continue that story, we would not expect tranexamic acid, at first thought, to help with brain bleeding in trauma, yet the early data from the crash studies suggests that it probably improves outcomes. Again, a randomised controlled trial is ongoing, but the early data of nested studies inside an RCT suggests that tranexamic acid probably helps. Those are examples, but, as for public pressure, I cannot think of anything off hand.
Q20 Dr Whitford: There are many, from Vioxx, which made it all the way through into standard use and then was causing heart attacks, or valproate in the epilepsy field.
Do you think that part of the issue, resistance and fear is that this was a schedule 1 drug? As doctors, we use ketamine, heroin and all sorts of drugs that on the street would have a value, but because they are already in normal practice we do not bat an eyelid. I wonder if the fact of cannabis having been a schedule 1 drug is adding an extra layer of fear and resistance among doctors.
Professor Dame Sally Davies: There is an emotional overlay that is aggravated by the kind of to‑do about cannabis on the street—“Is this the beginning of a slippery slope?”, which no one wants it to be, and people’s perception of cannabis. It is not sorted by our education system, because it is the first controlled drug coming in, yet we were taught to manage the other controlled drugs in medical school and then as young doctors. It will take time to change doctors’ perceptions and it is not helped by the fact that there are herbal medicines and extracts, and we will have to learn for each one what is the balance between cannabidiol and THC, how that impacts and what should be done going forwards. For each product, they will need different RCTs for the licensing.
Chair: We are going to talk a bit more about public opinion and behaviour.
Q21 Johnny Mercer: The BPNA said that part of your report is misleading, in specific relation to what Paul was talking about around childhood epilepsy. How would you respond to that?
Professor Dame Sally Davies: I was interested to see that. They have a right to their opinion. I have reviewed literature that I believe is well founded and I have given an answer. This is a problem with science: until you know exactly where you are, you get people on either side, and they come closer and closer and then you get an answer. That is a routine part of scientific discourse.
Q22 Johnny Mercer: There seems to be quite a lot of confusion in constituencies like mine about what the options are around medicinal cannabis at the moment and whether or not people can access it, what the benefits are and so on. Do you think the Home Office could have done more or should be doing more to tackle that challenge?
Professor Dame Sally Davies: My role was to say that there is enough evidence to move it from schedule 1 to schedule 2. It was not to give guidance to specialist doctors. They have to come together to look at the evidence for themselves as groups.
There are a number of barriers to prescribing. It starts with the evidence base that is not good enough, but we are all concerned about giving licensed medicines. We have concern about cannabis because it is so many different things, and there are many different things. That said—I am sure you will be talking to the NHS—they have pulled together to make sure that there can be a supply that comes in, that there is a way of prescribing it and that it is available.
Q23 Johnny Mercer: Will there be some sort of effort to inform the public about what the options are, what the efficacy of it is and whether or not it is likely to work?
Professor Dame Sally Davies: As soon as we have any data, of course we will share it with the public—that is very important; but we do not have any more data than is out there.
Q24 Johnny Mercer: It has become a bit of a cause célèbre in constituencies like mine. Some of us who see constituents looking for this sort of thing do not have detailed scientific knowledge of it, and we are up against that line from people like yourself and the Home Office as to what the boundaries are, so that we can inform them and so that they understand what the options are. You think we will get there once the evidence base comes out, do you?
Professor Dame Sally Davies: I wish we knew the answers now. I would love to tell patients, “It works with this side‑effect profile,” or, “It doesn’t work,” or, “It works for a few.” We do not have that evidence base. Until we do the randomised controlled trials, we will not have it, but I want to make sure that you recognise that we are not sitting on any knowledge or evidence that we have not shared with the public.
Q25 Johnny Mercer: Is none of that evidence available anyway in the US, or the other states?
Professor Dame Sally Davies: No.
Q26 Johnny Mercer: They have done some pretty extensive trials, haven’t they?
Professor Dame Sally Davies: No, they are not particularly extensive; that is the trouble. Where they are extensive is for the licensing ones, so in the States they have licensed Epidiolex and Dronabinol, and we have licensed Nabilone and Sativex—Sativex is not cost‑effective, according to NICE. Those all have an evidence base, but one of the problems in this area is that each one will need to be licensed separately. Take statins. Each company produces one, two or three; each drug has to be licensed and go through its own research process separately.
Q27 Johnny Mercer: What could we do to streamline that? Are there any options available?
Professor Dame Sally Davies: There is no shortcut. We have to find out how it works and what the impact is. If you look at the side‑effects reported to the MHRA, we know that for what we have out there—cannabidiol, Epidiolex and Sativex—we have had 79 reports over the years of adverse drug responses. In fact, there are nine fatal ones for Sativex. When we look at what they are, it probably will not be the Sativex; I think it is people with multiple sclerosis dying of something else, but we have to work through that steadily and collect the data, short term and long term, and analyse it very carefully.
Q28 Chair: Are there any final comments, Alette, that you would like to make, because I am conscious that we have not asked you very many direct questions? Are there any key points you would like our Committee to hear this afternoon?
Alette Addison: That is fine, thank you.
Q29 Chair: Are there any further points that you would like to make, Sally?
Professor Dame Sally Davies: I hope we can do the trials because, without those, how can we help the patients? That is what we are all here for, so please help us.
Chair: Thank you both very much for coming.
Professor Dame Sally Davies: Thank you.
Examination of witnesses
Witnesses: Genevieve Edwards, Professor Barnes and Peter Carroll.
Q30 Chair: Good afternoon and welcome to our second panel this afternoon. Could I ask you to introduce yourselves and say who you are representing today?
Genevieve Edwards: I am Genevieve Edwards. I am from the MS Society. We are a charity of people with MS—researchers, volunteers, fundraisers and campaigners. Our ultimate goal is to find a cure for MS, but while we pursue that we are also very keen to make sure that people have the treatments they need to help manage their MS. Clearly, cannabis‑based medicinal products fall into that category. We did some research in 2016 with 4,000 people with MS. We looked into the evidence for the effectiveness of those and we consulted our medical advisers. All of that led to us changing our policy to recommend that it be decriminalised.
Q31 Chair: Thank you. We will come back and explore that in more detail in a minute.
Peter Carroll: My name is Peter Carroll. I founded a campaign with colleagues called End Our Pain when we met some patients who were suffering from very distressing conditions and felt that medical cannabis could help. Last summer, we helped run the campaign for six‑year‑old Alfie Dingley, with his mother Hannah Deacon, which we feel played a significant role, along with other campaigns, in changing the law.
We represent about 45,000 people across the country who have signed up to our campaign registering support, and today is particularly pertinent because I am joined by the families of 16 severely epileptic children; many of the mums and dads are sitting behind me. To be honest, I am in a situation where I thought our job as campaigners and advocates was done on 1 November, and it was time to move on. I am shocked and horrified that we are in a situation where the law has changed but cases like Alfie Dingley’s would not qualify to get a prescription under the new guidance.
Q32 Chair: That is something we are going to explore with you specifically in more detail shortly.
Professor Barnes: I am Mike Barnes. I am a neurologist and a professor of neurological rehabilitation. I have been involved in cannabis work for about 15 years, initially with Sativex, which we have heard about already, and more recently with cannabis in a broader sense. I am a part of the lobbying campaign—part of the End Our Pain campaign—and I obtained the first prescription for cannabis for Alfie Dingley, pre‑legislation change on 1 November. I have been involved in trying to lobby for and develop medical cannabis for a long time.
Q33 Chair: Thank you, all three of you, for coming. I am sure you heard the evidence from our first panel, particularly the point made by Professor Dame Sally Davies, the chief medical officer, that there cannot be any shortcuts and we have to follow a process of randomised controlled trials in order to be able to establish the evidence base for safety. Would each of you give us your comment on what you feel the current evidence base tells us about the efficacy and safety of medical cannabis, starting in the same place as we started with the chief medical officer?
Genevieve Edwards: I mentioned that we had reviewed the medical evidence and consulted our medical advisers when we changed our policy in 2017. They agreed very much with the findings in the CMO’s report, that there was conclusive evidence that it can help in MS for pain and spasticity. MS is unpredictable and very different for everyone, but these are very common symptoms. They can make it really difficult to manage daily life. That led us to change our policy.
We agree that more evidence is needed—very much so—and we would like to see proper data collection set up alongside, so that we can learn as we go. We would like to see randomised controlled trials to help us to understand the benefits, but we need a plan for all of that. People are struggling with daily life right now. The change in the law is wonderful, and we welcome it; but what is the plan for what comes next?
Peter Carroll: I would like to challenge the proposition. I understand that evidence from randomised controlled trials is very important; it is the gold standard, but I do not think it is appropriate to base the entire future path solely on randomised controlled trial data. Dame Sally Davies herself said that we have to wait maybe three or four years before that kind of high‑quality, gold‑standard data is with us. How do you explain that to the parent sitting behind me now who is—and you may disapprove of this— sourcing a full plant extract cannabis, bringing it into the country and treating her child with it, and the child has improved dramatically? That is her random controlled trial and her own local doctors in the NHS have said they see the improvement; they have written it in clinical notes. Then they say, “But we are not going to prescribe it.”
We have to take a broader view of the evidence, because there is a point where multiple anecdotal stories build up to a pattern of evidence, and it seems absurd to me that we have to wait three, four or five years for trials to be produced when there are real‑life cases now. I confronted the BPNA a few months ago. I showed them the story of Alfie Dingley, who had 150 seizures a week, each potentially life threatening, and now goes 300 days without a single seizure, rides a bike and goes to school. Does he have to wait for a randomised controlled trial? Does Indie‑Rose, the child I was speaking about a few moments ago, have to wait four or five years? We have to have a broader view. The medical community quite rightly has a very high regard for RCT data, but to do that exclusively to the exclusion of a broader pattern of evidence and to sacrifice the wellbeing and health of children while we wait for that is unforgivable.
Professor Barnes: I agree with that. Cannabis is a plant and it does not lend itself very well to the standard pharmaceutical approach. It is not a single molecule that we can compare against a placebo. There are over 2,500 varieties of cannabis, each with a different structure of cannabinoids and terpenes, each with subtle differences. Which one would you pick for the standard pharmaceutical model? I agree with Peter entirely that we need to take into account a range of other evidence. We need to take into account anecdote, and if there are tens of thousands of anecdotes they build up to some form of evidence.
We need observational trials, and we need an audit of people who are already on cannabis medicine to see what is happening to them. I agree totally that we need randomised controlled trials, but I want to make one point: it would be very difficult to conduct those studies, for the simple reason that to prescribe cannabis you would start with a high CBD product, generally speaking, for any indication. If that worked, fine. If not, you would build up the proportion of THC bit by bit, so eventually some people might need a relatively high THC with CBD component. You move from one to the next and the next until you get a response.
The totality of that prescription may well be, and should be, very positive against placebo, but it is not the classic double‑blind placebo‑controlled trial where you pick one medicine against placebo. If you do that, it will not work. Let’s take pain. Around 20% of people with pain respond to a high CBD product, around 20% to a more balanced product, and so on, to about 20% responding to a high THC product. If you take one of those products, you will stand a 20% chance of success, which is not likely to be positive against placebo. If you take the whole lot, it will be positive against placebo.
It is not beyond the wit of man to design studies around that, but I want to make the point that cannabis is not just cannabis, and a lot of doctors do not understand that. Cannabis is a whole family of plants, and we need to take that fact into account when designing our studies.
Q34 Chair: Presumably one of your concerns about people using street supplies is that they simply do not know what they are getting.
Professor Barnes: Exactly. The street supply generally is high in THC, because that is what recreational users seek; they seek a high. Generally speaking, street cannabis is very low in CBD, sometimes non‑existent. It is very high in THCs, 20%, 25% or even 30%. Also, you do not know what is in it. Some people get it into their mind that medical cannabis is the same as street cannabis. Of course there is an overlap, but generally speaking, medical cannabis with the CBD that counteracts the THC effect is a different animal from street cannabis, a totally different animal. As to some of the side‑effects that we have heard about, quite rightly, such as damage to the developing brain, those studies are done on street, high‑THC cannabis, entirely different from medical cannabis with a CBD component.
Q35 Chair: Would you accept the concern that many people have expressed that the history of medicine is absolutely littered with anecdotally wonderful drugs that turn out to have very serious harms?
Professor Barnes: I agree with that, but cannabis is rather different in the sense that it has rather a lot of experience over thousands of years. It is not something that has come on to the street in the last few decades. In this country today, about 3 million people take cannabis, of which 1 million take it for medical purposes—1 million people. That is an accumulated great experience, so we know an awful lot about potential side‑effects. If some awful side‑effect was going to emerge, it probably would have emerged by now.
Peter Carroll: It seems to me perverse that doctors who undoubtedly are very caring and professional will routinely prescribe immensely powerful conventional pharmaceutical drugs. In fact, I was on an intensive care ward with one of the families behind me only a few months ago and I could see three syringes of very high‑powered pharmaceutical drugs being pumped into the child who was seizing, with the mother in tears. Those drugs, as was indicated in the previous evidence session, are for adults; they have not been tested on children. If you read their side‑effects, it is in black and white: they will kill you; they damage your heart and your liver. The medical profession has got itself on tram lines where it is prepared to do that, but there was an absolute refusal from the hospital to consider medical cannabis for that child. It is as if the focus on RCT is so rigid that it has completely distorted any sense of proportionality and common sense.
Q36 Chair: Do you think there is a case for having a different approach for very rare conditions with very serious side‑effects, say, from intractable epilepsy, and taking a different approach with those conditions than you might take with much more widespread conditions where it is easier to get results more quickly from a controlled trial?
Peter Carroll: Today, we were very fortunate that the Secretary of State for Health himself came to meet the 16 families who are with me. We are not talking about children who are a bit ill or who have mild epilepsy; some of these children have 100 seizures a day or more, and in fact it is so severe that they can even physically damage themselves. Because the illnesses of these children are so severe, we are suggesting to the Department of Health that you have to treat this cadre of families differently: rescue them, put them in an observational trial, pay for them to go to Holland, get some of the drugs from Holland and try them. There are all these nuanced arguments about, “Maybe we are going to damage their brain,” but that is probably happening already from conventional pharmaceutical drugs, the epilepsy itself or the physical harm that is being caused to them.
One of the families went to their consultant, who said—I kid you not—“I think it might work, but actually you should go to Holland.” If the family goes to Holland, they do not just pop over and get it: they have to go over and take a CBD product first and then be supervised by a clinician. I think Alfie Dingley’s family were away for about 15 weeks—£30,000. We actually have a doctor who is no doubt a very caring person—he must be because he is a paediatric neurologist—yet he is in a mindset, maybe from peer pressure, to say, “Go to Holland.” That man could just pick up his pen and write a prescription now. How have we got into this state?
Q37 Dr Whitford: As we were discussing with the former panel, if in the cadre of patients you are talking about the results are as dramatic as in the few children who are on it, do you not think that a randomised controlled trial that is designed to observe a dramatic difference can be broken quickly? In breast cancer, the Herceptin trial and others were stopped remarkably quickly because the results were so different between the groups.
Professor Barnes: It is right to say that would work, but you need to bear in mind what I said earlier; the design of the trial should not be just one of the many cannabinoids. We need to design a trial that allows that graduation, moving up the ladder, from high CBD to higher THC. If you take that into account, and I am sure that there are cleverer people than me who can design such a study, I totally agree with you.
Q38 Dr Whitford: Obviously, that can simply be part of the study, in that many drugs require to be introduced, whether it is from a low dose to a high dose, or, as in chemotherapeutic drugs, they move in all sorts of combinations from one drug to another. The experience that has been gathered anecdotally could be put into that because otherwise, as Dame Sally was saying, we are going to remain in the morass of anecdotally treating. That is fine and it helps, hopefully, the person in front of us, but it is not helping the children who will be born next year, the year after or the year after that because they will be back trying to get it.
Professor Barnes: I agree with that, yes.
Q39 Dr Whitford: Can I ask you particularly, Professor Barnes, whether there are any barriers and challenges to research, particularly accessing it from the manufacturers?
Professor Barnes: Yes.
Q40 Dr Whitford: Are they happy to get on board, or are they willing to contribute the drug, which is often the case in traditional pharmaceuticals?
Professor Barnes: I believe they would be very willing to take part in clinical studies. They obviously want to get into the UK for commercial reasons. It is a very profitable sector—of that there is no doubt—as experience in Canada and Germany has shown, so I think they would be very willing to take part in some sort of pooled exercise to promote and fund appropriate studies. I have no doubt about that.
Q41 Dr Whitford: Apart from the fact that studies of different cannabis‑derived drugs would be in different conditions, which applies equally in many areas of medicine, what do you think, looking at barriers and challenges, of the idea of trying to have a very small number of specialist centres within the UK that develop the expertise? If families are travelling to Holland, living there and having to buy it for thousands of pounds, travelling to Leeds, Birmingham, London or Edinburgh would not be so difficult if they were then accessing a trial on the NHS.
Professor Barnes: I quite agree. I think in the short term—how short is short, perhaps a year or two?—there are going to be very few cannabis physicians who are properly trained to prescribe. There is no doubt about that and it is a very sensible model to develop a small number; we may only need 50 or 60 doctors grouped in regional centres, where they can act as a regional centre of excellence for prescription, for the audit that follows it and for involving people in studies. That is an excellent idea and hopefully the medical community will realise that it can be helpful, and slowly but surely other doctors in other specialties will be willing to prescribe. Working in partnership with a cannabis physician and the appropriate specialist or GP is a very sensible model.
Q42 Dr Whitford: Is that the model that is developing? Obviously, many patients and families will be trying to access through their general practitioner, which is unlikely to be the access point for a long time, so is there any action coming from Government, from the Department of Health, to try to push that, so that we develop small pockets of expertise?
Professor Barnes: There is just one thing, before I let Peter get a word in edgeways: we formed the Medical Cannabis Clinicians’ Society, which is now a group of 60 doctors, as a peer support group. Hopefully, over the coming months, we will get those pockets of excellence around the country. That is what we are doing at the moment, actively promoting our society.
Peter Carroll: Dr Whitford asked a very specific question: is there any sign that the Government and the NHS are working to get centres of some kind? From my perspective, no. Families are routinely told, “We can’t do it, we’re not allowed to do it, we don’t want to do it.” We are not aware of a single co‑operative trust anywhere in the country actively reaching out to experts like Professor Barnes, or to us as a support group. We are not aware of any positive developments at all. It is simply a shattering experience for the families.
Q43 Dr Whitford: We heard from families that many who managed to access it under licence last year would now be excluded. Do you think that there is a need to have an ongoing licensing system at the moment as an interim?
Peter Carroll: No, I am not sure about the licensing system. When we put Alfie Dingley through the licensing, goodness me was that a process. They actually sent—was it?—a firearms officer to check the security of the house. We are talking about a bottle of medicine this big with a very low concentration of THC. Then we were threatened with a £20,000 bill for the licence, which was quashed. It is overly bureaucratic. What has to be done in the first instance for epileptic children is an urgent trial right now where the Secretary of State, Matt Hancock, says, “I don’t care what my officials tell me. I am not letting these children suffer. Get that observational trial to get the pressure off.” That is the first thing that has to happen.
Q44 Dr Whitford: Would you accept what I was saying about a randomised controlled trial that is dramatically different? You literally believe that the difference between the placebo group and the treatment group would be obvious within a couple of months. Would that take us further forward than an observational trial where everyone says, “Yeah, but it was only an observational trial”?
Peter Carroll: Yes, but there is a benefit of the observational trial; I would not want to be the person who said that child cannot have the drug and they have to have the placebo.
Q45 Dr Whitford: It is blind, so neither doctor, the patient nor anybody—
Peter Carroll: I love every one of the families we fight for. I could not suggest—
Q46 Dr Whitford: That does apply, I have to say, to cancer patients who also do not know if they are getting the cancer cure or not. Many of them may have spent five years on a drug that later proves not to have been the beneficial drug, whereas, if the dramatic responses that are described are shown, it should be obvious to the independent data monitors. If you are going from 100 fits a week to one or none, it should be obvious literally within a month or so, and it has moved you further. Would you accept that?
Peter Carroll: I am not that expert in the construction of different types of trials. The only thing I can say with certainty is that, given the anecdotal evidence that exists from the children last summer, combined with the evidence from across the world that Professor Barnes has talked about, these families should be given the right to try it now.
Q47 Dr Whitford: I understand that, but also, as a doctor, I have seen patients who have been damaged by things that look good, as the Chair pointed out. We have debates here on MeSH, on drugs and on all sorts of things—Primodos, valproate, or whatever you like—that were prescribed in absolute good faith, and they were licensed drugs that had been through a lot of process.
Peter Carroll: I totally accept your point. With the cadre of families I am talking about, the illnesses are so severe that it would be a wild stretch of imagination to think that any harm—it would be unthinkable in my mind that medical cannabis at low concentration THC could do anything that is—
Q48 Dr Whitford: But when would that change? There will be a child born next week who has the same condition, and the week after and the month after. At what point do you say, “We treat this cadre differently,” and then suddenly at some point you say, “Okay, any new children who develop this are going to be in a randomised controlled trial”?
Peter Carroll: I hope that the observational trial would be so powerful that we would not need the RCT, but I am not a doctor. I am a scientist, a physicist by training, but I am not a doctor. I can only say with certainty that I want these families helped. I do have one more—
Q49 Chair: Genevieve is keen to come in as well. I will come back to you, Peter, but I am keen to bring Genevieve in.
Genevieve Edwards: Thank you. I agree with many of the points raised. We estimate that there are about 10,000 people with MS who could benefit from these treatments for whom other treatments are not working, and that is specifically around pain and muscle spasms. I put on Twitter that I was coming here, and I have heard over the last few days so many people expressing their frustration and confusion and the feeling of false hope that has been raised as a result of this. They go to see their clinicians and are turned away either for unlicensed treatments, or for Sativex if they are outside Wales. One of the effects of this sort of confusion over what the plan is, and when they might reasonably be expected to get it, is that people are being forced back into the illegal black market where, as we have said, you do not know what you are getting—you do not get the strength, the quality or the right dose—and that frightens people.
Aligned with that is the fact that we know that smoking makes MS worse; it can make your daily symptoms worse and it can speed up your disability. We are really concerned about that. We are very keen to make sure that this can be available responsibly but in a responsive way because people are desperate.
Q50 Chair: Peter, you had another point you wanted to make.
Peter Carroll: I agree that a responsible approach has always to be the guiding principle. The comment I wanted to make is this. Part of our role as advocates and campaigners is to talk about the human experience. The situation, when families approach the NHS and their trust, is absolutely shambolic. I have seen a letter from a senior pharmacist in the north of England saying that it is illegal to bring these products into Britain. For heaven’s sake, did they not watch the news last year? It is quite shocking.
A commissioning group that wrote back was completely confused between CBD and THC, telling me that it was not possible to prescribe CBD. As you well know, you can buy the lowest concentration of CBD in Holland & Barrett. This is a shambles. Somebody needs to get a grip of this from the top and make it happen for patients.
Chair: Phillipa has a question on procedures.
Q51 Dr Philippa Whitford: It is on what the barriers and difficulties are in actually getting it. Maybe we could start with Mike. What should we change in procedures that would make it easier to use, easier to access?
Professor Barnes: The main barrier, to be honest, is education. There are bureaucratic barriers, but I think they can be overcome. I think most doctors do not want to prescribe because they do not understand the nature of cannabis. They do not understand what dose to give or in what format to give it. We can overcome that with an educational programme; there are one or two around at the moment. I would like to see how Health Education England or other jurisdictions develop, with experts, appropriate training programmes, and I know there are some doctors—quite a few—who will be happy to prescribe once they know what on earth to prescribe.
The second barrier is the guidelines. I am sure that the Royal College of Physicians and the British Paediatric Neurology Association felt they were doing a good job in providing those guidelines. Personally, I think they are too restrictive, rather negative and focused on double‑blind placebo-controlled studies, as we have heard, so I think producing guidelines that are a little bit more balanced is necessary. You kindly mentioned those being produced today by the Medical Cannabis Clinicians’ Society and the all‑party parliamentary group, so it is a group of doctors who have produced them. They sent a pre‑draft to the Committee, but this is now the final version, if at some point I could put that to the Committee. Hopefully, they are still balanced and sensible guidelines, but they are a little bit more attuned to cannabis than the existing guidelines. I think that will be another barrier; doctors can refer not only to those guidelines but to slightly more balanced guidelines as well so they can make their mind up with perhaps a little bit more balance themselves.
Q52 Dr Whitford: What about the barrier of the fact that it is an unlicensed drug and therefore a doctor has to sign a personal liability form? That is one thing if it is an old drug that is now unlicensed because nobody makes any money out of it, and another if it is a drug that, as you say, is 100 drugs.
Professor Barnes: Yes, that is a very good point. Many countries have gone along a slightly different licensing route. In Holland, there is the Office of Medicinal Cannabis, for one example. They have accepted the fact that it is not a straightforward pharmaceutical compound and it needs a slightly different view of licensing. We are trying to force it down a pharmaceutical licensing route and I do not think it comfortably fits a pharmaceutical route, to be honest. We should give some consideration to a different form of licensing so that doctors do not have to take personal responsibility for prescribing an unlicensed medicine.
Q53 Dr Whitford: Do you think the NHS could be taking the liability rather than them? When sentinel node biopsy came in, I had to sign one of those forms for the blue dye we inject into breast cancer patients, even though it was completely proven, and it took me about a year to get the hospital to take the liability. Do you think something like that might help?
Professor Barnes: I do indeed. It could be some form of alternative licensing system that does not either unlicense or license, so that there is something in between for cannabis.
Q54 Dr Whitford: But it does not change the licensing; it just changes the personal liability. To sign away your house every day is not something that will go down very well with the hubby or wife.
Professor Barnes: It is a barrier, you are quite right. Some doctors are prepared to overcome that barrier and just sign—I would, for example—but there are many, understandably, who would not. I agree with you.
Q55 Dr Williams: I want to ask a little more about the guidance you mentioned, Mike. In what way is the guidance that is being issued tomorrow different from the ABPN, RCP and ABN guidance? That is my first question. My second question is: are there any competing interests behind that guidance? That is just to give you the chance to have that out in the open.
Professor Barnes: Thank you. The guidance being produced at the moment is about paediatric epilepsy only, and the Royal College of Physicians guidance was about pain, and nausea or sickness in chemotherapy. These are broader. This explains a little about the background of cannabis, explains some of the terminology, and at a fairly high level goes through the evidence for all the other conditions that may be considered. It is much broader‑based guidance, which I hope is helpful to the prescribing community. The Medical Cannabis Clinicians’ Society is totally independent. This was produced with some support from European Cannabis Holdings simply to print the thing, but it is totally independently written; I wrote most of it.
Q56 Dr Williams: You said it was also being issued by the APPG.
Professor Barnes: It has also come out from the APPG on medical cannabis under prescription.
Q57 Dr Williams: The funding of the APPG is also relevant.
Professor Barnes: Yes. I cannot speak exactly about the funding, but the secretariat for the APPG is from Peter.
Peter Carroll: As well as running End Our Pain, we provide secretariat services to the APPG on medical cannabis under prescription. We have always made it clear that we are funded. I need to give you a few seconds on the story of End Our Pain. We came up with the idea for it because we met some patients and we had no money to fund it. We then got some funding from a think‑tank called Volteface, who funded us for about nine months. Then we had no funding for several months, and we are now funded by a man called Neil Mahapatra from Kingsley Capital Partners. He funds most of our campaign.[1]
Q58 Dr Williams: Are there links between him and any companies producing medicinal cannabis products?
Peter Carroll: I believe he has future plans to do that. I think he may have a company that he has recently formed, but I understand that it will be two to three years before there are any products. We have always had that on the website and declared it.
Q59 Dr Williams: I am just making sure that you have the opportunity, as we are talking publicly about guidance, to make sure that people understand.
Peter Carroll: Yes, I totally get that. I have a more general comment on the guidance, if I may. I cannot help but use anecdotes, because I think that is how you tell a story. To my knowledge, there is only one private paediatric neurology prescription in the UK. The doctor who wrote that, in a private hospital, was so nervous about writing it, in light of the guidance from organisations such as the BPNA and the national health service, that we had to work extensively with her to reassure her that she was not breaking the law and she was not going to get into trouble. She was constantly thinking, “Is it okay to do this?”
We have been to the highest levels of the GMC and the highest levels of the NHS, and they have written to us, in these files of letters I have here, saying that, whatever the guidance says, clinicians have the right, if they take everything into account, to take a holistic view and to write the prescription, but we are in a situation where feeling in the community is so powerful that they do not feel able to do that. One thing that could be done is for the NHS and for the bosses—the top people of the medical professional bodies—to come out and say, “Yes, we have given you guidance, but if you see these children and you judge, all things considered, that you can write the prescription, it is perfectly okay.”
The feeling of going against conventional wisdom and the guidance is very strong, and trusts are, frankly, just saying, “No, you work in our trust; you are not doing that.” The trusts are blocking it. That is not healthy.
Q60 Johnny Mercer: Can I ask about the money? What problems are there with the funding and availability of medicinal cannabis products, Genevieve?
Genevieve Edwards: At the moment, NHS England has said that trusts need to fund it. To take a step back, there is no clear and secure supply chain for these medicines. When people go to see their neurologist, they are told, “I have no idea where to get this from or who pays for it.” There is a lot of confusion at clinic level. In order for trusts to fund it, they need a budget line in place and there isn’t one at the moment. It will take a while to get the system in place and sorted, but what we would like to see quickly—there is a cross‑departmental working group on it—is a strategy that starts to unpick some of this stuff so that people get the further research that we need, and professionals know how they can do it, what they can prescribe, how it is being paid for and who is paying for it. At the moment, that is really unclear.
Q61 Johnny Mercer: What would you like to see happen, Genevieve?
Genevieve Edwards: We would like to see pain and spasticity specialists being able to prescribe these treatments, or specialists in the other conditions, and get them to people in a timely fashion.
Q62 Johnny Mercer: In terms of the money, what would you like to see happen?
Genevieve Edwards: My guess is that there are actually more people who could benefit from this than has previously been expected; 10,000 people with MS is probably right, maybe an underestimate. If you are dealing with a very small number of children with severe epilepsy, you could maybe manage that on a trust‑by‑trust basis, but you would need to put a more realistic estimate together to decide where the funding stream should realistically sit.
Q63 Johnny Mercer: Peter, you look like you’re itching to get in.
Peter Carroll: I am sorry, it is just that, having met the families and seen the patients, I cannot help it. On the money side, the brutal reality is that medical cannabis is very cheap, because if you look at some of the cases like Alfie Dingley, it has transformed his life, and he now takes no other conventional, or very few, anti-epileptic drugs, so there is potential for a net saving to the NHS. Think how expensive it was for him to be hospitalised every single week of his life, and then he goes 300 days without a single seizure. I think the financial argument is heavily towards trying to embrace medical cannabis and make it work.
Genevieve Edwards: What we are seeing, though, with Sativex, for example, which is a licensed treatment only available on the NHS in Wales, is that people with MS are trying to scrape together the money to pay for it themselves, and that is about £500 per month currently. That is why NICE is deeming it unaffordable. We hear from people that it improves their condition by 40% to 60%, for example, but they have only been able to afford seven months’ supply in four years, so we need to sort out the funding. It is not realistic that people who are unable to work are scraping together their benefits to try to pay for treatments that they desperately need.
Johnny Mercer: Slightly moving on from the money thing, if I may, Chair—
Q64 Chair: Mike wanted to come in as well.
Professor Barnes: It is a very quick point. I think it is important that a body—maybe NICE is going to fulfil that—looks at a proper health economic analysis, not just taking into account the cost of cannabis, which is expensive at the moment but will come down when more prescriptions are issued, but taking into account the other points that colleagues have made. You save about 25% of opioid prescription costs when you introduce cannabis. That is evidence from the United States where individual states have done that. You save on anti‑epileptic drugs, you save on anti‑anxiety drugs and, of course, you save on hospital admissions. I suggest that you could introduce cannabis to the national health service at zero net cost, or close to it, if all those other factors were taken into account, but we need the evidence for that and that is what we do not have.
Q65 Johnny Mercer: On the evidence point, what did you make of the previous panel where we were essentially told that that sort of hardcore base of evidence is not there? As I understood it—I have a very loose knowledge of these things—there are some fairly widespread trials going on abroad that have seen legislators in other countries, such as America and elsewhere, feel comfortable enough to make the process start happening. What do you make of the fact that we are not in that position, and we cannot seem to use that evidence base for families over here?
Professor Barnes: We definitely should use that evidence. At the moment, there are 128 trials of cannabis ongoing worldwide. We should not forget that other jurisdictions—sensible jurisdictions, if I can use that word—Canada, Australia, Germany and other European countries, such as Denmark, have introduced cannabis legislation and allowed doctors to prescribe, and they are prescribing with more freedom than we are here.
I think we are a little bit obsessed with UK‑based evidence. We need to take into account global evidence. I am sure people do, but I think we need to take everything into account and learn as much as we can from other countries that are now three, four or five years ahead of us.
Peter Carroll: Slightly changing the tack of that answer, and going back to the individual cost, the father of the two‑year‑old child who has the private prescription I referred to earlier—the one we all fought so hard to get—has to find at least £1,000 a month every month for that medicine. I have an adult patient in the north‑east who has been going over to Holland and bringing the stuff in. A consultant has written a prescription but will only do it on a private basis. She too is paying £1,000 a month—Lara Smith. When she walks, it is like she has constant electric shocks. It is unthinkably cruel. Those prescriptions could and should be written now on the NHS under the reschedule.
Chair: Derek, did you have any points you wanted to make?
Derek Thomas: Johnny stole my question.
Johnny Mercer: I am sorry, I didn’t realise that that was his question.
Q66 Derek Thomas: Mike, you mentioned the OMC earlier—the Office of Medicinal Cannabis.
Professor Barnes: In Holland, yes.
Q67 Derek Thomas: My question was going to be about what we can learn from other countries and what we can implement here to accelerate. Peter’s passion is absolutely right; we need to move, and I know you are all keen to get this done. We need to move quickly. I have constituents who contact me about this quite often.
What should the UK Government and the Department of Health be doing, looking at what is happening around the world, to see how we can accelerate in the right way here in the UK? Are there things that you can clearly demonstrate that can help us to accelerate things?
Professor Barnes: There are two or three answers to that, briefly. One is teaching programmes. In the States, there are several good-quality cannabis teaching programmes for physicians and clinicians. They are more comfortable about prescribing because they have been through an accredited teaching programme. We could learn from and duplicate those, and make them a bit more UK‑centric.
As we have mentioned, it is a plant product and because of the difficulties of the plant, I think there is a role for a slightly different office of medical cannabis, like they have in Holland, where they look at evidence in a slightly different way and can approve products that are slightly different from the normal pharmaceutical route. That will help to oil the wheels. It could be a subdivision of the MHRA—whatever format is appropriate—but as I said earlier, we are trying to force a plant product with multiple cannabinoids, thousands of different varieties, down a single molecule pharmaceutical route, and it ain’t fitting.
Derek Thomas: That is helpful. It is good for us to take that on board.
Q68 Mr Bradshaw: You have answered a lot of the questions I was going to ask in your very good and comprehensive replies, so thank you, and thanks to the families for coming.
Can I clarify one or two things? Professor Barnes, you said earlier that 1 million people in the UK currently take cannabis. Was that in England or Britain?
Professor Barnes: I believe it is in the UK. It was a survey from the United Patients Alliance; someone from it is sitting behind me. I think there are 3 million people taking cannabis every day, 1 million for medical purposes.
Q69 Mr Bradshaw: How are these people accessing the cannabis?
Professor Barnes: Illegally.
Q70 Mr Bradshaw: These people are being driven to criminality by the medical establishment’s refusal to move on the issue.
Professor Barnes: Yes, that is right. There are now about eight private prescriptions written in this country, so eight of the million are legal and 999,000, or whatever it is, are illegal.
Q71 Mr Bradshaw: Epilepsy and the death of young people from epilepsy is a major and growing problem. Is that not the case? Could you give us any figures on that?
Professor Barnes: I cannot give you figures on the death rate for epilepsy, but it is significant.
Q72 Mr Bradshaw: It is one of the major causes of death in young people.
Professor Barnes: It is one of the main causes of death in young people.
Q73 Mr Bradshaw: And it is growing.
Professor Barnes: Yes.
Q74 Mr Bradshaw: Would it be right to suggest that people are dying unnecessarily, because they are not getting access to medical cannabis?
Professor Barnes: Sadly, that has to be correct, yes.
Q75 Mr Bradshaw: When you went to see the chief medical officer, Sally Davies, after the law was changed—I don’t know whether it was your evidence or from one of the other organisations—you were told that it would basically all be fine and that this was the change you needed; yet in her evidence to the Committee earlier she seemed to be suggesting that the law was a change to allow trials. What was your understanding of the purpose of the law being changed? I think the public perception was that it was going to make this easier.
Peter Carroll: I might be able to add some context. Shortly after the law was changed, and the realisation dawned that actually prescriptions were not forthcoming, the APPG arranged a meeting with the most senior figures in NHS England. Sir Mike Penning MP, who has been a great advocate for this, held that meeting. I went as the secretariat.
We all left that meeting, and I think I can quote advisedly what was said, thinking that medical cannabis would become part of business as usual. It was just an unlicensed medicine, like the many other unlicensed medicines that are in use and, yes, there would be a bit of teething trouble and time to settle in. At that meeting, we said that we were detecting that that might not be the case, and that there would be a much more systematic refusal and objection to prescribe. I think, personally, that the top levels of the NHS want it to be business as usual and an unlicensed medicine, just like many others, because it has great advantages. I referred to cost previously. Something has seriously gone wrong because it is not business as usual.
Q76 Mr Bradshaw: According to some of the evidence we have seen, it has got worse and gone backwards: people who were getting it are now being deprived of it. Is that the case?
Peter Carroll: I personally have not come across that. That may be the fact I quoted earlier, when you allowed me a few opening comments, that the family of Alfie Dingley, for whom we went to all that trouble to obtain a special licence—only Government could do this—just got an email saying, “We have revoked your licence.” The full context was, “We have revoked your licence because you do not need it now because you can get it through the NHS,” but, guess what, the trust that actually looks after him locally refuses to prescribe. We have had to construct a workaround, straining every letter of the Home Office regulations, to allow Alfie Dingley to keep a supply. His trust said no.
Q77 Mr Bradshaw: Do you think that hopes were unjustifiably and unfairly raised by the Government?
Peter Carroll: No, I do not think it was unfair. The Government did the right thing. The Home Secretary listened, and there was a consultation on the evidence—the high-profile cases of Billy Caldwell, Alfie Dingley and Sophia Gibson. They were genuine cases and the Government, for once, did the right thing and did it quickly. No, I do not think they were raising expectations.
What has happened is that hopes have been correctly raised, because this offers a lot of hope and benefit to a lot of people, but we have now moved across to implementation and the honest reality is that it is a disaster. It is just not working. The families sitting behind me now should be getting prescriptions, going home and watching their children, hopefully—it might not work for everyone—improving day after day. I do not think it was wrong to raise the expectation: it is wrong not to implement it.
Q78 Mr Bradshaw: What has been the reaction of those families to the fact that it is not working?
Peter Carroll: Devastation. A member of our team liaises with family members, and it is tears every single day. I do the campaign, but in my spare time I help them write letters to their local trust begging for a second opinion. I say to families, “Please write to your MP. Get your MP on board; they can point out to the trust that the clinicians can lawfully prescribe.”
It is shattering. They are caring for kids who are suffering horrendously anyway. How dare we put them through a bureaucratic assault course and treat them sometimes almost with disdain, as if they are an irritation? How have we got to that system when everybody in the system probably really cares? The system needs to be got hold of by the scruff of the neck and shaken down from the top. I can promise you—please excuse my passion on this—that we will not stop until they get sorted. If it takes a campaign for every single individual child, like we did for Alfie Dingley, we are going to do it.
Q79 Chair: Can I pick up on one previous comment? There is a difference between the children who are suffering severe intractable epilepsy and what should happen for the wider picture of research. If we give an impression that for everyone who has suffered a sudden unexplained death from epilepsy it could have been prevented had cannabis been available, it would be unfortunate. I do not think that is necessarily the impression that was meant to be given.
Peter Carroll: I would not want to give that impression.
Q80 Chair: We simply do not know the answer to that question.
Peter Carroll: Can I say, though, that should that happen, and they have been denied the right to try it, how are we going to feel then?
Q81 Chair: Absolutely, but the point I was trying to make was this. How do you think we can best push forward with genuine research to say what the role of cannabis is more widely in the treatment of epilepsy? Would you be supportive of a rapid roll‑out of clinical trials that look at the wider issues about its place in the treatment of epilepsy?
Peter Carroll: I would, but forgive me for attachment to the particular group of families. I want them to get it now, and then we can work together to get a more sophisticated programme of trials and research.
Chair: I completely understand. Lots of colleagues want to come in. Martin was waiting to come in, and Philippa and Paul. Is it on the same point, Martin?
Q82 Martin Vickers: Yes, in part. It is also reflecting on what I have heard over the last hour or so. Clearly, particularly Peter, you are very passionate, and I have met constituents who have family members who suffer, or suffer themselves, so I can understand where you are coming from.
It seems to me, given what we heard from Professor Davies and what we have read in other evidence, that one can understand why Government Ministers have reservations about moving forward in the way you would like. It troubles me that what we have heard during the course of the evidence is that much of the guidance is amiss, because, clearly, there are health professionals, pharmacists, doctors and so on who are unaware of exactly what the position is. Surely, we could move forward a little bit by improving that guidance and the education that Professor Barnes mentions. Are there Administrations, other countries and the like that you would take as a model for that, so that we can at least get to a halfway house?
Professor Barnes: Two or three countries lead. In Canada, they are now well ahead in medical terms, and I know they have also added recreational, which is a different issue. There are lessons to be learned in Canada. Australia as well has been on this route. I think there are lessons to be learned in Denmark, Holland and Germany. They are the five countries, if I had to pick. A review of how they have done it, and how they have done it wrong in some cases, would be very useful to the UK.
Genevieve Edwards: I agree that there are some good examples that we can learn from in countries that are further down the road than us. We were disappointed when the interim guidance came out. It recommended against the use of cannabis‑based products for pain and it did not specifically address spasticity in much detail, despite the evidence in the CMO’s report.
We would love to see NICE get it right and nail it when the actual guidance comes out in October, and we would love to see patients round the table because, to my knowledge, there were no patients involved in drawing up the interim guidance and I know of no particular instances where involving patients does not make things better. We would really love to see patients’ voices and experiences taken into account, and a real streamlining of the process from product to patient. In Australia, for example, they have some good examples of how they have made that more streamlined than our current, understandably clunky system. It will take a while to get right—we understand that—but we would love to see the plan for doing it.
Q83 Dr Whitford: To go back to sudden unexpected deaths in epilepsy patients, it is the second commonest cause of neurological death, particularly in young patients, but they are a totally different cohort from the cohort who have intractable epilepsy. These are unexpected deaths, so maybe I can ask you to clarify that, Professor, being the neurologist in the room, because I would not like it left that we were implying that all these patients have uncontrolled epilepsy, or that it was somehow an expected death.
Professor Barnes: Sure. Many people, children or adults, with epilepsy are very well controlled on licensed products. The vast majority, 80%, are controlled on one single anti-convulsant drug. A small number need two or more, and then we are talking about very tiny numbers who need multiple drugs and do not really respond to anything.
In the less controlled population, there is a risk of a SUDEP, as it is called—sudden unexpected death in epilepsy. You can die in the context of having a seizure, but you can die outside having a seizure; you just drop dead and no one fully understands the mechanism for that. It is fortunately quite rare, but hopefully if the epilepsy comes under control—coming back to the cannabis issue—the risk of death either during a seizure or in between seizures, in the SUDEP syndrome, will lessen and we will save lives. I am not talking about huge numbers, but we will save lives.
Q84 Dr Whitford: Has there been any research in patients who are thought to be at risk of SUDEP with cannabis?
Professor Barnes: Not as far as I am aware.
Q85 Dr Whitford: We have gone from intractable epilepsy, which is very much where this conversation started, to a different cohort of patients.
Professor Barnes: I am not aware of studies like that and there are very few studies on adult epilepsy, full stop. We talked about epilepsy, quite rightly, as there are many families behind me that have real problems, but, looking at cannabis as a whole, we should not forget that 80% of prescriptions are for chronic pain and other conditions such as PTSD, anxiety, depression and so on.
Don’t get me wrong. It is a very worthwhile cause for the children with intractable epilepsy, but we should not just focus on those cases; we should focus also on the totality of helping people with a lot of chronic disabilities.
Q86 Dr Williams: I want to understand the issue with the epilepsy guidance to make sure that I am clear about it. Currently, the only licensed product is Epidiolex.
Professor Barnes: It is not licensed in the UK yet; it is licensed in the States.
Q87 Dr Williams: The current guidance suggests that people should prescribe Epidiolex off licence. Is that correct?
Professor Barnes: At the moment, yes, there is a compassionate use programme. The company making it, GW Pharmaceuticals, has given out 150, I think, for people to use.
Q88 Dr Williams: Epidiolex is almost totally CBD.
Professor Barnes: It is an isolate. It is 99.9% CBD, which works very well for some people, but others need the full extract—the cannabis with other components still left in.
Q89 Dr Williams: Which may be THC and maybe other components.
Professor Barnes: There will be a little bit of THC and it will have other components, yes.
Q90 Dr Williams: You are suggesting that there should be more freedom to try different legal but unlicensed products.
Professor Barnes: Exactly. Quite right.
Q91 Dr Williams: They have not yet been through any randomised controlled trials, but there are many individual cases in which they have been shown to bring improvement.
Professor Barnes: Correct, yes.
Chair: Thank you for coming this afternoon, and thanks to all those joining us today who have been affected by this issue. Thank you.
Examination of witnesses
Witnesses: Professor Cross, Dr Malik and Professor Sisodiya.
Dr Paul Williams took the Chair.
Q92 Chair: Welcome to our third panel. I am Dr Paul Williams. I am going to chair the final panel because Sarah has been called away. Could you start by introducing yourselves and saying who you represent?
Dr Malik: I am Imran Malik. I am a consultant psychiatrist. I am representing the Royal College of Psychiatrists, which is a professional medical body that sets and raises standards for psychiatric practitioners in the UK. I am a member of the expert reference group working on a position statement on the role of cannabis-derived medicinal products in mental health.
Professor Cross: I am Helen Cross. I hold the Prince of Wales chair of childhood epilepsy at UCL, Great Ormond Institute of Child Health and Great Ormond Street Hospital. I am a paediatric neurologist, and my main focus for the past 25 years has been research and clinical care of children with complex epilepsy with ongoing seizures. Due to my standing, I have led on a number of various bodies, and I have driven co‑ordination of the European reference network, EpiCARE, which I hope will continue. This is recognition that epilepsy is not a single condition. Epilepsy is a symptom of many rare diseases, and therefore it tries to co‑ordinate new interventions, which has been the main focus, for children and adults with early onset epilepsy.
Professor Sisodiya: I am Sanjay Sisodiya. I am an adult neurologist and an epileptologist. I am chair of the Association of British Neurologists epilepsy advisory group and I am here on behalf of the ABN today.
Chair: Thank you very much. Our first questions are going to be around the evidence base and the future of research.
Q93 Dr Whitford: Can I start with you, Professor, and then we will add in. Don’t feel the need to repeat if you agree, but do add things, if you can. What would you say the current evidence base tells us about the efficacy and safety of medicinal cannabis?
Professor Sisodiya: It is important to start by expressing the fact that there are between 150,000 and 200,000 people with difficult-to-treat epilepsy in the UK. It is important that we try to find new additional treatments to stop the seizures that people are having. Among those, we have evidence for the efficacy of cannabidiol from three randomised controlled trials in two rare epilepsy syndromes, Dravet syndrome and Lennox‑Gastaut syndrome. There is good evidence for the effectiveness of those products in those epilepsy types. That is where the main evidence base is. There are non‑randomised studies published in many journals for other combinations of cannabis‑derived medicinal products in various other epilepsies, but the best evidence is for those two syndromes.
Q94 Dr Whitford: Of the 200,000 with difficult-to-control epilepsy, what proportion would be covered by those two syndromes?
Professor Sisodiya: We do not exactly know, because some of these syndromes have not yet been diagnosed in people who have them, especially in adults. I only see adults and am speaking about adults. We know that there are adults who probably have these conditions in whom the diagnosis has not yet been made. It is difficult to be clear about that. We think that probably one in 12,000 people have Dravet syndrome, so it is not that uncommon, and Lennox‑Gastaut may be slightly more common. It is a group of syndromes. It is important to remember that Lennox‑Gastaut syndrome is not one condition. There are many different possible causes for that condition.
Q95 Dr Whitford: What would you say is the gap in the evidence base where research is clearly needed?
Professor Sisodiya: We know about the evidence for cannabidiol in those specific epilepsy syndromes, and we know that on the short‑term basis of the trials that have been carried out. They have been relatively short term. We do not know about longer-term treatment schedules. We do not know about combinations of different cannabis-derived products, and we do not know about other epilepsy types, beyond Dravet syndrome and Lennox‑Gastaut syndrome, so there is quite a lot that we do not know. We do not know about interactions with many other anti-epileptic drugs, for example. Speaking as an adult neurologist, seeing people who may become pregnant, we do not know about the effects in pregnancy, and that is a very important thing to consider.
Professor Cross: As my main area of research focus has been early intervention, or new interventions into early onset epilepsies, I have been involved with the trials of cannabidiol from the beginning. I was the first to prescribe Epidiolex in this country as an unlicensed medication, and was involved in the development of the trials, and indeed was an investigator and an author on two of the three trials.
I think we need to explain that this is cannabidiol, because some of the confusion is that cannabidiol, as pure cannabidiol with minimal THC, has never been a schedule 1 drug. It is a schedule 4 and therefore not a controlled drug, whereas the legislation changed the position of cannabidiol with THC, which is where it would enable the research to go forward. We were able to do the trials as it was not a controlled drug, and it was sponsored by GW Pharmaceuticals, who produce the medication.
The studies were done in two rare complex epilepsies—Dravet and Lennox‑Gastaut. The reason for choosing a narrow type of epilepsy was being able to define quite clearly the clinical features of the children and adults going into those studies, and then defining the endpoints quite clearly, minimising the number of individuals who needed to be included in the studies to get the power of the study at the end, from a statistical point of view. Although we accept that there are wide ranges of different complex epilepsies, we chose those two particular types because they are particularly well defined, and we could include those and get some degree of answer, which we did, with cannabidiol.
The way it is thought to work is not thought to be specific to Dravet or Lennox‑Gastaut, and it is likely that it would work across other complex epilepsies, having proved that it worked in those two. The issue is that that is now where the evidence base is and that is where the definition is.
When it comes to how we move forward, it has been shown in those studies that cannabidiol can be effective. It is not effective in every child with Dravet and Lennox‑Gastaut—40% show more than a 50% reduction of seizures—but the issue is then whether anything is added by the THC. As we have heard, cannabis is not one but many different plants, many different products. There is clear evidence that cannabidiol does not affect learning and cognition. The issue is that in animal studies THC, as has previously been pointed out, has been seen to be proconvulsant as well as anticonvulsant, so could it cause seizures? The issue is also about the effect on the developing brain and how we monitor that. We then come to the issue of what percentage is required: how do you move forward with that? These are the areas we need to look into. That is why we want to do further clinical trials.
Clinical trials do not have to be in rare disease, big randomised controlled trials. They could be small, careful N of 1 studies. There is different methodology. We all agree that different methodology has to be applied to this group of rare diseases. The difficulty is that we have to design it. We have to determine which product, and we have to obtain the product. The product costs a lot of money, so many of the funding agencies where you might apply would not consider funding the product, the placebo or whatever we need. Therefore, there is an issue about how that funding goes forward. Yes, we have calls to the NIHR, and we are trying to work towards getting protocols, but again it is defining which category of type of epilepsy, and indeed getting agreement on how the product might be achieved, or might be obtained.
There are many different barriers, not least funding. We can design, with collaboration, appropriate trials in different groups of types of epilepsy, maybe considering the type of product we need to use, but there is an issue about developing the protocols and what will be available for funding and so on.
Q96 Dr Whitford: Do you think the companies that produce these drugs would be likely to be happy to give them, as is often the case in traditional pharmaceutical trials, or do you think they would not?
Professor Cross: We have been in discussion with one particular company, but it has taken us six months to get them to be interested in doing that, and I know the experience in another country was that they pulled out of those trials early on. I have had correspondence with Canada where they are proposing a particular study, but I have yet to see the protocol, and the difficulty is where the products are going to come from too.
Q97 Dr Whitford: Dr Malik.
Dr Malik: As we have heard, there is a debate about the dearth of evidence on the epilepsy side of medicinal cannabis use. In mental health, the evidence is even weaker. There is some evidence on the role of medicinal cannabis in behavioural and psychological symptoms of dementia. There is some evidence of herbal marijuana being used in PTSD. However, these are largely based on observational studies or case reports. On the behavioural and psychological symptoms of dementia, studies have shown that there is an element of neuroprotection from cannabinoids, which are psychoactive substances, and that they reduce neuro-degeneration. However, because they are early findings, there is an appetite for further research in the area.
Q98 Dr Whitford: What do you think would be the potential health harms that might be associated with using cannabis?
Dr Malik: As already identified, the active component is THC, which is proven to be useful. The challenges are that we know that there is clear evidence of harmful effects on mental health of cannabis, which is driven by THC. If the proportion of THC increases, it has a negative impact on mental health. That would be the challenge with regards to studies in psychiatry.
Q99 Dr Whitford: Within mental health, touching on dementia, PTSD, anxiety and depression in other mental health areas, what would you pick out that would be the first area where you would probably think you wanted to focus? For your study, where would you want to look?
Dr Malik: I think it would be the behavioural and psychological symptoms of dementia. We heard earlier from Peter how frustrating it is and how desperate families are when individuals are in dire need of treatment. BPSD—the behavioural and psychological symptoms of dementia—are the non‑cognitive symptoms of dementia that present in a very challenging fashion, and actually lead to institutional care, which leads to a reduction in quality of care for the families and individuals involved. That is the area that could see the most difference, and that is the area where it has come out that it is likely to reduce neuro-degeneration, and is more neuroprotective in their cells.
Q100 Dr Whitford: How do you respond to concerns from previous panels that the current procedures to access cannabis are not working?
Dr Malik: I hear that. The frustration was quite palpable in the room. I have similar cases in mental health. I see patients who use cannabis for recreational purposes, as well as for medicinal purposes. The majority of them are using it for recreational purposes.
The people who use it for medicinal purposes are looking for treatment for fibromyalgia, insomnia, or resistant PTSD symptoms, and they are desperate. I get challenged day in, day out in clinics. The recent hype of medicinal cannabis has not helped the situation. It has given very high hopes. Based on what we have heard, the evidence has not been that strong. In clinics when we talk to them, we are actually thrashing their hopes, which have been raised by social media.
Correct me if I digress. What does not help is that we in this panel here today, the Committee members and the panellists, have interchangeably used the words cannabis and medicinal cannabis, which sends a very wrong message. All the recreational users of cannabis in my clinic are reinforced by the fact that the cannabis has a medicinal use, and they do not see the difference between medicinal cannabis and street cannabis. There is a perception of reduction in the risk associated with cannabis usage in the streets. We are seeing people we would counsel to refrain from using cannabis, but they are using more under the umbrella or the light of this new evidence being thrown at them. We sit here and say that medicinal cannabis is useful. They hear, “Cannabis is useful.” The language has to be drafted in a way that differentiates the two, and there is a need for a campaign.
Q101 Dr Whitford: Thank you for bringing that point out so clearly in the hearing. What do you see as the particular barriers and challenges to the research you would want to carry out in the mental health dementia and PTSD areas?
Dr Malik: The challenge in our area of mental health is that the research is common across any medication you want to trial, as opposed to our colleagues who are neurologists. They have a very specific, well-defined diagnosis; they can do a scan and an EEG and get to the diagnosis. They may disagree with me; I see shoulders being shrugged.
However, ours is more abstract when it comes to the diagnosis, and the challenges are more difficult. In real life, you come across multiple comorbidities. For example, day in, day out, I see patients who have epilepsy but have mood disorders associated with that. When we are to prescribe whatever form of medicinal cannabis we get approval for, we do not have any drug interaction information available to us. In real life, they are on multiple drugs, so they would be on antidepressants, antipsychotics or a number of other physical health-related medications. As a clinician, when I stick my neck out to prescribe something that does not have a licence, I still do not know what the interactions are.
Coming back to your question, the challenges would be to find pure cases where there were no other confounding factors and to trial this one pure form of medicinal cannabis on them. Then there is the challenge, which was raised by Professor Barnes earlier, that this is a natural product with a number of cannabinoids—over 100 types of cannabinoids—and the ratio of CBD and THC will have an effect. To find the right set of drugs to try, and the right set of patients to try them on, would be a great challenge.
Q102 Dr Whitford: Obviously, that would be similar to the phase I trials of almost any drug—which combination is safe and efficacious—before you go wider. That can apply in multiple pharmaceutical areas.
Dr Malik: Yes.
Q103 Dr Whitford: That is why we end up not just doing a trial. Many members of the public think there will be a big trial and that is the end of it, whereas actually it is a small group, a bigger group and then a huge group. That is what we normally do.
Dr Malik: It is just the start of it, yes.
Q104 Dr Whitford: Can I come back to you, Helen? What do you think are the barriers and challenges particularly on this issue? The public, in the sense of patients and their families, were expecting dramatic change, but they are not getting it, so there are barriers to getting medicinal cannabis prescribed, whether or not in a trial.
Professor Cross: It is important to say that I fully understand the desperation of the families. I see that every week in my clinic. All I see is children with complex epilepsy, with a multitude of other problems associated with that. With complex epilepsy come learning disability and behaviour problems. It is difficult for the families, and I acknowledge that.
What we are trying to do is look at safe new treatments. With the initial announcement in July last year, and then the subsequent change in legislation and the announcements in November, there came a real expectation on the part of the families, and not just the 16 families we have heard about but every family in my clinic, that we could just prescribe it. It was a natural treatment, and therefore that is what they wanted because it was different from what they were on. Probably 70% to 80%, if not more, of my clinics now are taken up with explaining the position. Obviously, we discuss the complexity of the condition and what the next best treatment is, but cannabis and cannabidiol come up with every single one.
What we are all here for is to strive for better treatments for our patients; that is exactly what we want. About 60% or 70% of those I explain it to understand; we have trust that we are going forward in the treatment together. There is a small percentage where it has become quite adversarial, and it is not a way forward with regards to treatment.
We want to prescribe something that we know is safe or that we can monitor in the appropriate way. Yes, we have the compassionate use programme with Epidiolex, but that is limited to Dravet and Lennox‑Gastaut syndromes. It is being considered as to when it is licensed and whether it will be funded, and that may also be limited to Dravet and Lennox‑Gastaut syndromes. We don’t know. There is a perception that they can walk in and get the prescription, walk out and it is fine.
I acknowledge that there are pockets of expertise, and I probably have most expertise with cannabidiol, not necessarily with the other products. The issue is what product has pharmaceutical standard, how we go forward with that, where we get it from and who is going to pay for it. Who is going to pay for it may be a bit of a moot thing, but I want to raise it. Parents come in expecting that everything is prescribeable on the NHS, and they do not understand that, No. 1, we have to decide which product. Even Epidiolex, which we can get through the specials programme, is not necessarily available on the NHS; we have to have local agreement for funding.
When it comes to other products, because I want to know about clinical trials and how I move forward, I inquired with my pharmacy. I have been told that, if I decided I wanted to prescribe the product with THC tomorrow, I could not get it through standard procedures even if I prescribed it tomorrow. There are many different barriers. It has been put forward that it is the doctors who are stopping this, when actually a multitude of things are putting the barriers in place. That has made relationships between us and some patients quite difficult.
Q105 Dr Whitford: I talked in an earlier panel about the barrier perhaps to clinicians being that this was, if you like, associated with an illegal street drug and that was adding an extra layer of concern. You used the words “natural medicine”, and I know from being a breast cancer surgeon that there is a perception that a natural or herbal medicine has no side‑effects, whereas, as we know, from digitalis and many others, many of our original medications came from plants, and, if it can work, it can also have side‑effects. Do you think there is a kind of softer layer of perception on both the clinical and patient or family sides that is getting in the way of the understanding?
Professor Cross: Correct me if I have got the question wrong, but I do not think there is really a fear because it is a controlled drug. That is not what is bothering physicians. It is the issue about knowing what we are prescribing and, ”First do no harm,” which is what our premise has been. We acknowledge that there is concern about recurrent seizures, that recurrent seizures can cause damage, and the drugs themselves. We do not want side‑effects and we are weighing that up all the time, but it is the same with this. We need to be secure about what we are giving and that we are giving the right stuff, of the right grade and reliability.
The other thing we have, of course, is the hemp oils that are being bought over the internet by families who are desperate. I try to relay that, No. 1, they are not necessarily reliable in their content. They have been looked at and studied from batch to batch; some may contain nothing but CBD, and some THC, so what they are getting is fluctuating on a day‑to‑day basis. I have seen several families where the seizures of a kid with epilepsy have gone for a while, they have come back for a while and gone for a while and then come back devastatingly. They were taking, supposedly, the same product.
The issue is not only the fluctuation in what they are getting but the interaction with other drugs. Even a small amount of cannabidiol may interact with liver-metabolised drugs. They may not be only on anti-epileptics; they may be on other things, stimulants or whatever they need. It is about being secure that you can have a consistent product that is reliable and you know what you are giving, to make sure that you can monitor the effect and the side‑effects.
Professor Sisodiya: I agree with a number of those points. There is a disconnect between what appeared to be being made possible and what was actually possible. It is still the case that most of my colleagues would like to be able to use new agents for the people they see with difficult-to-treat epilepsy. We would all like to do that. There is the compassionate use programme, and six adult neurology centres across the UK are taking part in that. Colleagues are keen to be able to prescribe cannabidiol, as an example. In fact, in the adult neurology sphere there is a very limited supply, only 30 prescriptions across the UK. That is it for the many people with treatment-resistant epilepsy that we would like to be able to treat. I do not think there is reluctance to consider its use.
I think my colleagues are keen to be able to use it, but, as Helen said, there are barriers. Those barriers are at many levels, including at the level of trusts that may not, for whatever reasons, allow us to prescribe the drug. There is a disconnect between what was said to be possible and what is actually possible in practice.
Q106 Dr Whitford: How do we go about getting that changed? Even if it is trials, you need secure access to the drug, or drugs, and what you are trialling needs always to be the same. There has to be a sustainable supply of the same balance. If you know what the balance of CBD and THC is for a cohort of patients, it has to be the same in all that cohort and timewise as well. How do you think we get through some of those difficulties, as well as things like funding or provision?
Professor Sisodiya: There needs to be a co‑ordinated discussion between the different parties who are interested in this, rather than maybe separate activity from the different entities. We all want the same thing. We need to join together in order to make it happen. We need to consider all of the different aspects, as has been said. There are different products that we need to be able to think about. We need to make sure that there is secure supply for these products. We need to be able to structure the trials in a sensible and sensitive way for what may be relatively rare epilepsies where perhaps more traditional structures of trials may not be so easy to manage.
Q107 Chair: Who should co‑ordinate that? We took evidence earlier that in the Netherlands there is the Office of Medicinal Cannabis. Do you believe that there is a need for that co‑ordinating body?
Professor Sisodiya: It is important to put this in the context of what is happening, for example, in the treatment of epilepsies. Cannabidiol is one cannabis product. It may be very helpful for some people with very difficult-to-treat epilepsies. There are equally other agents. I know we are not talking about other agents today, but it is important to put it in context. They might also be unlicensed but may be indicated for specific epilepsies, as an example. We have the same problems trying to prescribe those agents, which are probably also unlicensed.
In my view, it is part of a bigger picture that we need to be thinking about. For example, as we learn more about each individual type of epilepsy and we learn more about the biology that underlies it, we can work towards more rational treatments for those individual epilepsies. For some, it might be medicinal cannabis products and for others it may be repurposing cardiac drugs; for others, it may be something else. We need an overarching mechanism. It may be that this becomes part of that. For cannabis, specifically medicinal cannabis, there may be additional pressures to try to move ahead sooner. I do not know if I have an answer to who should co‑ordinate it, but I think it would at least be sensible for the different parties involved to sit together to try to establish it, which I do not think, to my knowledge, was how it happened initially.
Q108 Dr Whitford: Would it not be, from a medical point of view, more appropriate that it was a network group related to the disease, which is obviously what you would like, rather than a network group related to cannabis, in the way it is in the Netherlands, in that you have gone to the answer? You have decided cannabis is the answer, whereas in actual fact you need to be looking, and, as you say, there will be other new drugs, there will be other agents.
Professor Sisodiya: Yes. It is part of a bigger picture, as we move towards more personalised or precision medicine. We need to be thinking about mechanisms that enable all these things to happen, because there will be other people who require other agents, in the same sort of position, but maybe without the additional surrounding circumstances for medicinal cannabis. In fact, we do this to some extent already. We work across the UK and across Europe with groups of people who have the same type of epilepsy—I use that as an example—and establish what the right treatment for those individuals would be, and we structure studies across Europe to make that happen.
Q109 Dr Whitford: You mentioned, Helen, the particular syndromes within epilepsy, identifying that they will have a good chance of responding to CBD—Epidiolex—in the same way. Coming from a cancer background, I know we cannot help but test or identify, before giving any drug at all, the cohort of patients who are most likely to benefit from this version or that version, of that drug. Is research along those lines going on?
Professor Cross: There are two things. One is that we already have a network of specialist centres, particularly paediatric and adult neurology within the UK. The paediatric neurologists have an epilepsy interest group, just as the adult people do, and we could work together. We have already worked together looking at medication that, for example, perhaps has an adult licence, as is often the case before it has a paediatric licence, to try to gain data to see what children are actually demonstrating over time. We audit that on a regular basis. That is one coherent network from the work together.
There is no doubt that, if a study is going to happen, that is where the medical side should be driven. Now we do not do any research without family involvement in designing protocols, obviously working with clinical trials units, because they need to co‑ordinate things; but it needs to be driven from the medical side to define which outcome measures, or which best outcome measures, we need to look at, let alone which types of children. That was the main premise for the European reference networks, to try to get clinical trial readiness for rare diseases, knowing where the rare diseases were so that we could roll out standardised protocols. Another initiative, conect4children, was initiated in the UK but is a European‑funded IMI project that many of us are in. That is also looking at clinical trials in rare diseases to try to build up that work.
We have some of that background, but the problem we have in trying to get a protocol up and running as quickly as possible is that you have to go through the application for the money process, and that takes months to come forward. We had a question earlier about what you can learn from other countries. In Australia, the Government could not get Epidiolex, so they funded another product, a certain amount per physician; a delegated paediatrician or paediatric or adult neurologist has a certain number of prescriptions that they can utilise. I do not think that is the way to go, because it is like an open label, but you could look at it with regard to a set research protocol. More often than not, getting the product is the main stumbling block.
Q110 Derek Thomas: People behind you have sat here for a couple of hours now. They live this every day, some of them. What I take from this afternoon is two things. One is that we have to get this randomised controlled trial and we need to educate physicians better so that they feel more comfortable working with a non‑recognised drug at the moment.
You will be familiar with the commissioning through evaluation process that happened a few years ago. I have two questions. Do you need something like that? Do you need something like commissioning through evaluation, in order to accelerate what is going on from the NHS? If the drug is so expensive, why are the pharmaceutical companies not engaged in actually funding the randomised controlled trials? What is stopping them? It just seems that today we heard what needs doing, but no one is actually saying what is going to happen and when. I do not know if I am hearing it right.
Professor Cross: It depends what you mean by a pharmaceutical company, or whether it is a company producing a product that may or may not be of pharmaceutical grade.
This is my view. I think there is a plan for some of them to engage in trials but there is also a belief that there is lots of money, and that they do not need to do the trials because it is just going to be prescribed and therefore it is going to be okay. There are one or two companies that are discussing with us about doing the trials, but they cost a lot of money, and are they going to get their licence at the end? If it is going to be prescribed anyway, they may or may not need to. If they are based in countries where it is all legalised, they may not feel that they need to do that. That aside, there are some that are interested and therefore we are discussing it with them.
Q111 Derek Thomas: The commissioning through evaluation, where you give the drug, or in this case the medicinal cannabis, and then you evaluate as you go along, is already happening, but, if it is happening, it is happening at a tiny—I think we heard—
Professor Cross: It is tiny.
Q112 Derek Thomas: Do we need to apply some pressure?
Professor Cross: I would feel very reluctant not to do it under a protocol, with key entry points and endpoints and looking at the methodology. It would not be a big RCT in the traditional sense, but actually looking at rare disease methodology, looking at key cohorts of children and adults. I must not leave it to just children.
Dr Malik: If you do not follow a protocol, it will be again thrown out as poor evidence, so it is crucial that it addresses all protocols.
Q113 Mr Bradshaw: I would like to ask a question that Dr Whitford asked but from the other way round. Would we be making this difficult for desperate families whose experience indicates that it helps for any other naturally occurring substance, if it was not something that was prohibited and used widely recreationally? Do you not think that is having a chilling effect on doing something that would appear to be rational and would end this cruelty?
Professor Cross: I would like to emphasise that we have heard about the 16 families, but I have many other families in my clinic who have children who are recurrently seizing many times a day. They look at their children every day and we are trying to improve their care. The problem with any natural product is always the worry that, although it may be naturally produced, that does not mean that it does not have side‑effects and interactions with what they are on already. I can give an example.
I have done a lot of research into the ketogenic diet, which is a high-fat diet that has been around for over 100 years in the treatment of epilepsies, but I only did the first randomised controlled trial in 2008 and actually proved that it was effective in complex epilepsy. That is developed from natural products, but it has side‑effects and interactions that you have to look out for. It may be a naturally produced product, but the effect on the body is not necessarily natural. We have to bear that in mind with any product that we are going to put into a child or an adult, and again there are interactions with other things.
Q114 Mr Bradshaw: What about what we heard from the families and their representatives earlier? These children are already being subjected to very potent pharmaceuticals with very strong side‑effects that have not been tested and licensed for use on children.
Professor Cross: We acknowledge that in paediatrics traditionally we have licensed medications behind the adults. It has been easier to do big studies in adults with focal onset epilepsy. Therefore, we have necessarily ended up trialling some medications subsequently in children. We are not in the business of prescribing medication to stop seizures with side‑effects. If there are side‑effects happening, we have to evaluate whether it is the right drug. In some circumstances, it is better that children are not on drugs than on them because they are better off. Some do not respond to anything at all. We are constantly evaluating. There are many complexities around what causes learning and behaviour issues in the children. Yes, sometimes the medication may affect them and you have to monitor that, but the underlying cause of the epilepsy often is equally at fault.
Q115 Mr Bradshaw: We heard earlier that people are being driven to criminality and are dying because they cannot get access to medicinal cannabis. Has anyone ever died of a medicinal cannabis overdose?
Professor Cross: There are children who have been put at harm by being given cannabis, in the interaction with other drugs, let alone being given the actual product—full cannabis—because parents are not aware of the problem, yes.
Q116 Mr Bradshaw: Dr Malik, you talked about mental health and the impacts on mental health a little earlier. Are you aware of any evidence that medical cannabis has had a negative impact on mental health from countries where it is obtainable?
Dr Malik: There are no long‑term effects known of it. Short‑term effects are known in terms of cannabinoid-induced hyperemesis, which is excessive vomiting with cannabinoid; and cognitive difficulties in terms of poor concentration and memory difficulties. Those are all in short‑term studies.
I would like to emphasise what was said earlier about valproic acid. We psychiatrists have used that almost as much as neurologists have used it, for its mood-stabilising aspects, and out of licence for emotional dysregulation and personality disorders in women of child-bearing age. That has only been over the last couple of decades and we have recently come to know the evidence of its harmful effect in congenital malformations, and we are all backtracking, trying to find all the patients we prescribed the medications for.
There is a lot of pressure to rush into it. There is a lot of frustration and a lot of people are struggling, but we have learned the hard way, and from various other medications as well, that rushing into it is not the right answer. It was also mentioned that experiences have been the same in Canada and Australia. In Canada, the Federation of Medical Students actually issued a position statement in spring last year that there was a huge gap in their understanding in comparison with what was expected of them as they qualified to become doctors, and a similar statement was issued by pharmacists in America last year. If we are rushing into approval of something for which there is less evidence, there is less effort being made to educate people who are at the frontline.
Q117 Mr Bradshaw: But the families do not feel this is rushing into anything. They are desperate and a million of them are obtaining it illegally, or they are going abroad to get it. How on earth can you describe this as rushing into anything?
Dr Malik: There is a long‑standing perception of herbal remedies being accepted, and cannabis being accepted as one of those, and we see that in clinics day in, day out. There are people who when they come to us are only focusing on, “I have been able to sleep better,” but they forget the avolition syndrome, which is lack of motivation, being lethargic continuously. That is not as important to them at the time, when they have had a good sleep. Some people have anecdotal evidence. In my clinic, they tell me how beneficial it has been for their sleep, but they are disregarding the mental health side‑effects, which are blatantly obvious to us. There is that perception element.
Q118 Chair: In the last panel, it was argued that cannabis has been around for 1,000 years. Don’t you already know what the side‑effects of it are and what the effects are? Why do we have to be so cautious?
Dr Malik: That is a very good question. The best way to answer is that it is probably suitable for some but not for everyone who may be presenting with the same conditions. Let us take an epileptic child who has a family history of schizophrenia. On the vulnerability scale, that child is vulnerable to developing psychosis regardless of exposure to cannabis or not. So, if you expose that child to THC in their teens, you are accelerating, or increasing, their risk of developing psychosis, and the child may be considered to be ruled out for THC treatment. You identify cases, and identify a patient profile where it would be suitable and where it would not be suitable.
Q119 Johnny Mercer: Can I talk about the money again with this panel? What problems are there with the funding and the availability of medicinal cannabis from where you are sitting?
Professor Cross: It is not freely available on the NHS, whether it be cannabidiol, as in Epidiolex, or any other product. It is not prescribeable. The Epidiolex that we are prescribing is on the compassionate use programme, which is funded by GW Pharma, the company itself.
Q120 Johnny Mercer: If you get prescribed this in the UK, who pays for it?
Professor Cross: There may be a discussion and an application process for it to be funded, whether it be through the trust or through the local CCG, but, in reality, if it is Epidiolex, it is £25,000 to £30,000 a year and that is how much the market is.
I acknowledge what the earlier panel was saying about cost-benefit. You do not know what the effect is going to be, and there needs to be a trial period. As far as other products are concerned, there needs to be an agreement locally that it is going to be funded. In the ones you have heard about, I think families are actually funding it, as far as I am aware.
Dr Malik: We are talking about an unlicensed product. If we were talking about licensed products, at local level the cost matters. You may have a national statement to say such and such a drug should be considered for such and such an illness. However, at local NHS trust levels, medicine management committees assess the cost‑effectiveness, and they have to look at the other medications that are being used and how much budget is being spent on them. In line with that, they may or may not allow it to be prescribed at different NHS hospitals, so one particular NHS hospital may allow it, but down the road another may decline it.
Q121 Johnny Mercer: Can I ask a question about evidence without upsetting anybody? There is one thing I do not understand about evidence. We say the evidence is not there, and we need to do a trial to find out what is going on. Even to the average layman there is quite a lot of evidence out there. Other countries are looking at this, and, as was alluded to earlier, they are not tin‑pot countries: we are talking about America, Australia and Germany. Can you explain to me why that evidence is not good enough for legislators in the UK? I know this is not my subject matter or expert area, but I do not understand why, if there is evidence out there, we do not just go and get it for families who are crying out for this drug to be available.
Professor Cross: The only randomised controlled trials are with cannabidiol.
Q122 Johnny Mercer: Is that worldwide?
Professor Cross: Worldwide. The only randomised controlled trials are with cannabidiol, and they were multi-centre, multi-country, so they were led in the US, but the UK participated, as did several European countries and Australia.
When it comes to the other studies, they are large, open‑label studies, so there is no placebo control. With regard to, for example, Tilray and Dravet syndrome, of which there was a study of 20 patients published, it was open label, which meant that they were all put on it and monitored before and after. The percentage that had a benefit—in fact one died in that study of a SUDEP, even though they were on it—
Q123 Johnny Mercer: What is a SUDEP?
Professor Cross: It is a sudden unexpected death in epilepsy, as we discussed earlier. Of the other 19, 60% had an improvement, and when you look at randomised controlled trials, where they are completely blinded and nobody knows what they are on and you are assessing it, and you look at an open-label trial, that is probably comparable. That was a small study of 20. All the other data we have is open label. It is not randomised controlled trials.
Dr Malik: From a mental health perspective—
Professor Cross: That was in childhood epilepsy, yes, I am sorry.
Dr Malik: From a mental health perspective, there is no RCT, to my knowledge, that has been conducted. It is being used for PTSD in Israel and it has been used in 16 states of America, but the only things you have to go by are observational studies, some case reports. We talked about behavioural and psychological symptoms in dementia. There are eight reports collectively that comment on 117 patients, so there is no wealth of evidence.
Maybe I can stick my neck out and say within the safe walls of this Parliament that our American cousins across the pond are often quick to approve medication. We have colleagues working there who are talking very highly about some products now, which six months down the line we may get approved here if they withstand our trials—our robust testing. However, the majority of them fizzle away; we never get them here. I am not sure whether it is true for neurology or not, but for mental health medication they inevitably get licensed across the pond first and it takes some time to come to us, often with different restrictions and regulations, which are all welcomed for the safety of our patients.
Q124 Johnny Mercer: Is it not worth thinking outside the box of these randomised controlled trials? Are they the Bible for testing on all sorts of drugs, and you have to have that and without that the answer is simply no, and will always be no? Is there not an effort to look at all the other evidence that is available?
Professor Cross: Yes, we do look at it. There are systematic reviews and we look at the data, but from a regulatory point of view, they will be looking at randomised controlled trials. That is where we are at.
We are trying to move forward, and we have moved forward a long way in paediatric trials, for certain over the past five years, with the regulators in trying to say what evidence we require. There is the orphan drug registration, which means it is slightly faster track to get to that than previously, and we are trying to re-look at how we do trials in rare diseases because of that. We are doing that actively all the time, but, when it comes down to it, the regulators have a set bar that they want us to cross.
Professor Sisodiya: It is the industry standard, if you like, to have a randomised controlled trial, and the licensing depends on it, but there is an appreciation that they are not perfect by any means.
Q125 Johnny Mercer: Yes. There is no point having regulations if they do not work for the people who need them, but I am afraid this sort of old adage, “Those are the rules and we stick by them and put our fingers in our ears,” is not appropriate going forward.
Professor Cross: That is not what we are saying.
Professor Sisodiya: No. I do not think that is what we are saying at all. We are saying that randomised controlled trials are not our design, they are not our structures, but they are the structures that are established for licensing that we recognise are not perfect. There have been anti-epileptic drugs that have gone through randomised controlled trials and have been apparently shown to be effective, which in regular clinical practice, when many more thousands of patients get them, do not work or have other side‑effects, and they fall out of use. There are drugs for which that has happened. There is an appreciation that a randomised controlled trial, although it is an industry standard, is not perfect and that there is a need to think about different ways of doing this, especially as we begin to accept and understand the difference between different epilepsies.
Q126 Johnny Mercer: Who is doing that thinking and looking at changing the regulations? Who is at the cutting edge?
Professor Cross: Some of us who work in clinical trials all the time are involved in those discussions. We have an international body that works with the FDA and the EMA in liaising on that, and there is ongoing discussion all the time. I have talked about outcomes. Are seizures the only outcome for these families? Not necessarily. There is behaviour. It is about putting in lots of different outcomes. We are all actively involved in that too. There is constant discussion going on, and there is active discussion going on between the FDA and the EMA.
Q127 Chair: Thank you. We have to finish in four minutes, so the final question is about the guidance that is currently available. You will be most interested in the RCP guidance, and presumably the ABPN guidance and the ABN guidance. We have taken evidence that the guidance is too restrictive. We also know that NICE has been asked to draw up some guidance. Maybe we can have a final comment from you on what you think of the guidance from your organisations, or the organisations you are most interested in, and what changes, if any, need to be made.
Dr Malik: From the Royal College of Psychiatrists perspective, we have the expert reference group, which is currently meeting and coming up with the understanding of its role in mental health. As we stand, there is no other guidance available to psychiatrists for the use of cannabis-derived medicinal products in mental health. That is where we stand.
Professor Cross: From the BPNA, the guidance was written looking at the evidence base that it had at the time and was written to support the professionals. I think, as it stands, it is appropriate. It does not mean to say that, as a body, we are not looking at moving it forward, and that is certainly partly what we have been reporting today, but the guidance as it stands, I think, is guidance and it is there for the purpose, for our paediatric neurologists to utilise.
Q128 Chair: We have heard evidence that it has resulted in how many prescriptions being given for—
Professor Cross: I do not think it is only the guidance that has resulted in that. I do not think you can blame the guidelines totally for that.
Q129 Chair: You do not think that the guidance needs to be less restrictive.
Professor Cross: No, I do not.
Professor Sisodiya: I am only speaking, obviously, about the guidance for adult use of cannabidiol and cannabis-based medicinal products. I do not think that it is the rate‑limiting factor in the prescription of cannabidiol, for example. It is appropriate that colleagues who are perhaps not familiar with its use have some guidance on what dose to start with, how quickly to build it up, and what monitoring is required. People do not have that experience. We need to be able do that in order to keep our patients safe, especially with an unlicensed medication.
Q130 Chair: To be clear, Helen Cross, you think that we need more evidence base, and better availability of these medicines, and that there are issues around availability, so, even if they were prescribed, they are not available.
Professor Cross: Yes.
Q131 Chair: Are they the big things that you are saying need to change?
Professor Cross: Yes.
Q132 Chair: You said the guidance is not the rate‑limiting step.
Professor Cross: No. The guidance states that cannabidiol is recommended as the first line, because that is what we have as the evidence base. It says that physicians who do not have experience should not feel that they are put into a corner to prescribe something they are not happy with. That does not say nobody can prescribe it. I do not think you can say the guidance is the rate‑limiting step. For those of us who are involved in clinical trials, and actively trying to look into that, the actual development of those studies, monitoring our patients and indeed even obtaining the product and the funding are the major rate‑limiting steps.
Q133 Chair: Do you agree? Are they the rate-limiting steps?
Professor Sisodiya: I agree. I think the guidance is guidance, and we all do what we think is best for the individual patient in front of us, which sometimes means deviating from the guidance, but the guidance is not the rate‑limiting step.
Chair: Is there anything else you would like to say that we have not asked you about?
I thank our witnesses and everybody who has come in and listened so attentively to the evidence. We will have another evidence session next week, which you are very welcome to join, or you can tune into parliament.tv if you want to watch it. We will be compiling a report with our recommendations. Thank you very much for joining us today.