Legalisation of Medicinal Cannabis: Discussion

On behalf of the joint committee, I welcome Dr. Lorraine Nolan, chief executive, and Dr. Elaine Breslin, clinical assessment manager, Health Products Regulatory Authority, HPRA; Dr. Colin Doherty, a neurologist at St. James' Hospital, and Ms Vera Twomey, the mother of a six year old child, Ava Barry, who has been diagnosed with Dravet syndrome. The purpose of the meeting is to consider the possible legalisation of medical cannabis and cannabinoids. I am conscious that we will need to move along speedily because we need to finish by 11.30 a.m.

By virtue of section 17(2)(l) of the Defamation Act 2009, witnesses are protected by absolute privilege in respect of their evidence to the joint committee. However, if they are directed by it to cease giving evidence on a particular matter and continue to do so, they are entitled thereafter only to qualified privilege in respect of their evidence. They are directed that only evidence connected with the subject matter of these proceedings is to be given and asked to respect the parliamentary practice to the effect that, where possible, they should not criticise or make charges against any person or an entity by name or in such a way as to make him, her or it identifiable. I also advise that any submission or opening statement submitted to the committee may be published on its website after the meeting.

Members are reminded of the long-standing parliamentary practice to the effect that they should not comment on, criticse or make charges against a person outside the Houses or an official, either by name or in such a way as to make him or her identifiable.

I call on Dr. Nolan to make her opening statement.

Dr. Lorraine Nolan

I am chief executive of the Health Products Regulatory Authority, HPRA, and I am joined by my colleague, Dr. Elaine Breslin, our clinical assessment manager. We are pleased to provide a brief background on medicinal cannabis. The HPRA is the competent authority for the authorisation of health products in Ireland, which includes medicinal products. It is our role to ensure that where products can demonstrate they are safe, effective and of an appropriate quality based on clinical and scientific data, they can be authorised and supplied as medicines in Ireland. Medicinal use of cannabis is a broad term where part of the dried cannabis plant material, or products which have been manufactured from chemicals, known as cannabinoids, extracted from the cannabis plant, are used in medical treatment.

Cannabis under Irish law is considered to be a drug of abuse and is controlled under the Misuse of Drugs Acts 1977 to 2016. Under this legislation, cannabis and products that contain the psychoactive chemical, tetrahydrocannabinol, commonly known as THC, or its related derivatives, are subject to strict controls. Cannabis is prohibited other than in specified circumstances where all activities relating to cultivation, manufacture and supply of cannabis, and products containing THC, are subject to licence. Under this legislation cannabis and products containing THC are not viewed as products having medicinal use. However, a doctor could prescribe in limited circumstances, if granted a licence to do so by the Minister for Health. While it is generally perceived that our current legislative framework prohibits medicinal use of cannabis, this is not fully correct.

It is important to clarify that the cannabis plant also contains a range of cannabinoids some of which are psychoactive, which means they affect the mind, and some not. Examples of cannabinoids that are not psychoactive include cannabidiol, commonly known as CBD. Products containing non-psychoactive chemicals, such as CBD. are distinct in that these do not fall under the Misuse of Drugs legislation and its restrictions. In considering medicinal use of cannabis and the debate on the need for new legislation, we must be clear that this does not extend to CBD, which can be prescribed by doctors, without special licence.

However, regardless of the control status, if cannabis or its products make medicinal claims, they would be considered to be a medicine. In general, medicines are required to have a marketing authorisation enabling supply on the Irish market. The existence of an authorisation provides reassurance that a rigorous scientific assessment of the medicine’s quality, safety and effectiveness has been carried out by an authority such as ours. Based on this, the benefit-risk profile for the authorised medicine is both known and considered positive.

Ireland has authorised one medicinal cannabis clinical trial under a ministerial licence, which the company sponsoring the trial did not progress. We have also authorised a cannabis-based medicine which is known as Sativex. This contains the psychoactive chemical, THC, and also CBD. It is indicated for the treatment of multiple sclerosis. The product met the required safety, effectiveness and quality standards for authorisation as a medicine, and demonstrated clear patient benefit. The misuse of drugs legislation was amended in 2014 to allow for its prescribing, dispensing and supply. With regard to medicinal cannabis, the authorisation of Sativex and the earlier approval of an application to conduct a clinical trial, demonstrate that there are provisions within the existing misuse of drugs legislation that can enable patient access. In addition, the legislation can also be adapted to enable wider access, as in the case of Sativex, where this is justified based on scientific and clinical evidence.

With regard to current research we are aware that a number of clinical trials evaluating cannabis and cannabis products are being conducted within Europe and internationally. These relate to treatment of a range of conditions including chronic pain, psychiatric disorders and neurological disorders including epilepsy. Currently, some 30 such trials are ongoing within Europe. The majority of these trials involve adults. Some involve children and are investigating the use of products containing only non-psychoactive CBD for the treatment of epilepsy, including severe forms of this condition, which have failed other treatments. A product known as Epidiolex is the most widely used medicine in such trials. While the results appear promising, they have not yet been peer reviewed or independently evaluated by a regulatory authority.

While many countries have the same approach as Ireland, a number of countries have introduced changes to their misuse of drugs legislation to remove prohibitions which can, in certain circumstances, permit medicinal use of cannabis. Examples of where such changes have been introduced in Europe include the Netherlands, Croatia, Malta and the Czech Republic. Denmark and Germany have recently announced their intention to progress similar changes. Beyond Europe, Australia, Canada and a number of US states have introduced schemes for medicinal access. Internationally, the schemes in place are focused primarily on controlling the quality and supply, principally of dried cannabis for medicinal use, as prescribed by a doctor. Other than synthetic cannabinoids and Sativex, countries have not authorised medicinal cannabis as a medicine due to the limitations of currently available clinical data on safety and effectiveness.

In recognition of a growing demand for access to cannabis for medicinal purposes, it is, at this time, appropriate to consider whether patients' best interests could be served through enabling access to medicinal cannabis in Ireland. If on balance, it is considered that a less restrictive approach is appropriate for Ireland, in the absence of clinical data to allow the authorisation of cannabis, and related products, as medicines, there are a number of elements that such a framework may potentially cover. Based on international models and experience, these might include securing the quality of the cannabis plant which is cultivated, and can vary in terms of its chemical constituents and growing conditions. The framework would also have to consider patient safety and how that is achieved through appropriate medical oversight, while recognising that the requirement for access has been driven by patient demand. As such, patients and carers must recognise the limitations of the framework in assuring the safety, quality and effectiveness, as compared with what would be expected from an authorised treatment.

The HPRA has been requested by the Minister for Health to provide an expert opinion on medicinal cannabis and required policy and legislative changes. This is a complex issue which needs to be appropriately dealt with in order that all the needs of patients in Ireland who may benefit from medicinal use of cannabis can be considered. This also needs to take account of concerns that have been expressed on the potential harm from exposure to cannabis. We are currently in the process of convening a working group of experts to assist us with this issue. The conclusion of our work will be an advice to the Minister on the use of medicinal cannabis and, if warranted, possible frameworks based on international experience to address collective patient needs. If the Minister, following receipt of our advice, takes a policy decision to implement a new legal framework for medicinal cannabis, it will require time to develop, may require primary legislation and needs to be done in a manner that is effective and best meets both patient and societal needs. It would also require control of the supply systems for cannabis which have their own complexities. However, as I have explained, there is provision within the existing legislation for prescribing in limited circumstances. The HPRA would be happy to further explore, in conjunction with the Department of Health, how this could potentially be used to provide access to medicinal cannabis in the short term and in response to specific needs. We would be happy to keep the committee updated on our progress. I thank the Chairman, and we are happy to address any questions.

Dr. Colin Doherty

I am a consultant neurologist from St. James’s Hospital in Dublin with expertise in treating all forms of epilepsy. I am the national lead for the epilepsy programme in Ireland and senior lecturer at Trinity College school of medicine and a member of the International League Against Epilepsy, ILAE. I will give a brief review of the history of cannabis use for epilepsy and describe the science underlying its potential use as a prescribed treatment and I will attempt to outline a pathway for developing a consensus around potential prescribing practice.

In the history of cannabis use for epilepsy, while there are references to medical uses of hemp going back 8,000 years in China, Irish physician, W.B. O'Shaughnessy is widely acknowledged to have written the first modern scientific paper on medicinal use of cannabis in the Provincial Medical Journal published in 1843. Mr. O'Shaughnessy was born in Limerick in 1809 and moved to Calcutta with the East India Company where he observed the local use of cannabis for various ailments. He is now considered the father of the medicinal cannabis movement. In 1851, following his paper, the US Dispensary classified cannabis compounds as useful treatments for neuralgia and convulsive disorders. By 1860, the Ohio medical society committee on cannabis declared efficacy for infantile convulsions, epilepsy and many other disorders. However, the narcotic effects of cannabis led to unregulated recreational use and medicinal cannabis was caught up in the prohibition movement that lead to the banning of alcohol and other drugs.

In 1911, Massachusetts became the first state to outlaw cannabis. Other states quickly followed with marijuana prohibition laws and they persisted throughout the 20th century such that, by 1970, the US Controlled Substances Act was passed, classifying marijuana as a drug with "no accepted medical use". Countries throughout the world now have stringent laws and punishments for the possession and distribution of cannabis.

Let us consider the botanical and chemical aspects of cannabis use. The herb and its extracts contain more than 100 chemically similar compounds, called cannabinoids. It also contains over 400 other non-cannabinoid compounds. As we know, cannabis remains best known as a drug of recreational use and is consumed by approximately 150 million people around the world each day. Recreational use implies the ingestion of leaves, resin and oils of the Cannabis sativa plant, which has large amounts of the psychoactive form of the cannabinoid tetrahydrocannabinol, THC. It is cannabis which is rich in THC that causes the "high" people commonly associate with the drug. However, the indica plant produces a more fibrous compound that has no psychoactive effects, and this was also probably the first non-food crop grown by man, for the production of hemp rope, sacks, etc. Hemp is rich in cannabidiol, CBD, which is the form that appears to be useful for treating convulsive disorders. While the pharmacology of THC is considered to be reasonably straightforward, the pharmacology of CBD is extremely complex. CBD is known as a multi-target drug whose action is not completely understood.

Over the past 50 years, there has been a growing community of campaigners for more widespread and regularised use of medicinal cannabis. Among the most popular indications are chemotherapy-induced anorexia and chronic pain in cancer and multiple sclerosis. Of course, there have also been reports of spectacular reversals in the treatment of epilepsy leading to a chorus of calls from patients, carers and parents for a more thorough evaluation of the drug for epilepsy, and if proved useful, its legalisation. In 1996, California became the first state in the United States to legalise cannabis, for medicinal use only. Now cannabis is legal in 26 states in the United States.

I wish to consider the growing evidence for the efficacy of CBD in treating epilepsy. The first scientific reports in recent times did not appear until the early 2000s. After a number of case reports of success in treating epilepsy, the issue came to the fore in 2013 when Dr. Sanjay Gupta, CNN's doctor, broadcast a two-part documentary called "Weed" on medicinal cannabis use. The series features Charlotte Figi, a young girl from North America with Dravet syndrome, a severe genetic form of epilepsy that is often resistant to anti-epileptic drugs and puts sufferers at risk of sudden unexpected death in epilepsy, SUDEP. Some 20% of people with Dravet syndrome will be dead by the age of 20. Charlotte began to have seizures at the age of three months, and by three years she was having more than 300 per month. She spent three years in and out of intensive care units. Her parents moved to Colorado having researched cannabis and obtained a high CBD content oil that had a sudden and dramatic effect on the seizures. The Figis noted that the amount of CBD in each preparation was important, and they worked with a local grower family, the Stanley brothers, to perfect the strain that worked best. The product has now become known as Charlotte's Web.

This and other stories like it have led to unprecedented co-operation in open-label studies in the United States of Epidiolex, a purified phytocannabinoid form of CBD derived from the whole plant in the United Kingdom which is produced by the pharmaceutical company GW Pharmaceuticals. Results from 213 children and young adults who received Epidiolex, which is 99% CBD, in an open-label study were presented first at the American Academy of Neurology in April 2015. They can be summarised as follows. Some 9% of patients, or one in ten, with an average age of 11, became seizure free. The average number of seizures per month was approximately 100 but this number reduced to zero. Some 50% of patients saw a decrease in the seizure rate of at least 50%, so the number decreased from 100 to 50. Patients who had Dravet syndrome responded more positively, with a 63% decrease in seizures over three months. CBD did not work for all and was associated with adverse events, including drowsiness, in 37% and fatigue in 16%.

Two phase III placebo-controlled studies on Epidiolex have recently been completed. These are the types of trials usually required for licensing. Preliminary results were posted in a press released on 26 September 2016 on GW Pharmaceuticals' website. From having spoken to the researchers, I know one of the studies has been accepted for publication. The other has yet to be published. Therefore, they have not been published yet in peer review journals.

Despite increasing evidence in the scientific literature of the value of this almost pure form of CBD, there are calls for other as yet unproven forms to be made not only legal but also available for medicinal use. These forms have various levels of THC that adherents claim will improve its antiepileptic effect. The evidence for this is based on anecdotal reports of benefit in some children. While there may be reasons to be optimistic that such claims may have validity, there are as yet no controlled or uncontrolled trials being run to endorse such a position. Furthermore, recreational forms of cannabis with high levels of THC have been associated with psychosis in susceptible populations. Extreme caution, and significant evidence, will be required in determining the safe level of this drug to give to sick children.

Let me address issues concerning the availability of CBD in Ireland. Under Irish law, cannabis is not recognised as having any medical benefits. The most recent Misuse of Drugs (Designation) Order lists cannabis, cannabis resin and its derivatives as Schedule 1 drugs under the Misuse of Drugs Acts of 1977 to 2016. As a consequence, the manufacture, production, preparation, sale, supply, distribution and possession of cannabis are unlawful for any purpose, except under license from the Minister of Health for the purposes of research. The availability of various formulations for use in cancer, multiple sclerosis and epilepsy has led to calls for a liberalisation of the law in regard to medicinal use. In the past few years, a form of medicinal cannabis called Sativex has been specially licensed in Ireland for use to reduce spasticity and pain in multiple sclerosis but this has not been reimbursed by Government payment schemes, which may explain its slow uptake. The main form of cannabis that appears to work for epilepsy - high CBD, low THC - can be considered an unscheduled drug only if the THC level is no more than "trace". Nevertheless, a number of forms of high CBD, low THC oils can be purchased in retail stores in Ireland and imported online. However, since the drug is not regulated or designated as a medicinal product it cannot yet be prescribed by Irish physicians.

The use of cannabis to treat epilepsy offers a tantalising new horizon for severe disabling seizures. There is an urgency created by the community of families with severe epilepsy to complete a proper, sober and reflective scientific evaluation of the efficacy and safety of this drug. Initial studies are encouraging but not definitive. Already, it is possible to state with confidence that this drug will not work for everyone and will cause intolerable, but probably not dangerous, side effects in a few. For those for whom it would work, however, it may be life-saving. Despite the short timescale for these hearings, I have already consulted widely with Irish and UK colleagues and international researchers, including one of the lead researchers in the US studies quoted. As of the last count, only ten countries in the world have legalised cannabis for medicinal use and only one that I know of, Australia, has a proper national framework for medicinal prescribing for children with epilepsy.

In conjunction with those behind the national epilepsy programme and the Irish section of the International League Against Epilepsy, whose president is Professor Norman Delanty of the Royal College of Surgeons in Ireland, and with representatives from the pharmacology and therapeutics committee of the Royal College of Physicians of Ireland, we propose to work with the Health Products Regulatory Authority to determine whether such a framework for limited prescribing of pure CBD oil is possible based on the current level of evidence, with particular focus on the safety for children.

I thank Dr. Doherty. Would Ms Twomey like to make an opening statement?

Ms Vera Twomey

I will try. I did not come as prepared as my colleagues. I was going to print out a little photograph to show the members my daughter Ava. I brought a number of pictures of her on my iPad, one of which shows her after she had a seizure. Perhaps the members would like to pass it around. Ava has Dravet syndrome and is six years old. Dravet syndrome is an intractable form of epilepsy. Ava can suffer from anything up to 50 seizures per day. She was diagnosed when she was four months of age. We took her to Macroom to get her vaccinated at 11 o'clock in the morning and then brought her home. By 8 p.m. that evening, she had her first 45-minute seizure. We took her to hospital by ambulance and we were obviously terribly frightened. When we got in, a considerable number of blood tests and other tests were carried out. Ava's bloods were sent to Glasgow for tests. After a number of weeks, the results came back and we were given the diagnosis of Dravet syndrome. It is an intractable form of epilepsy that causes multiple seizures of all types, including absences, drop seizures and tonic-clonic seizures, which are the ones where the individual falls to the ground and shakes.

The photograph I have circulated shows Ava after having had approximately a dozen seizures. One can see quite vividly that she is in a considerable amount of pain. It is very frightening. When she has that many seizures, we do not know what the outcome could be. She could come out of a seizure with a dramatic loss of skills. That has happened before. When she was about two years of age, she had five seizures, after which she lost the ability to walk. It originally took us two years to get her up on her feet and walking but after having those seizures together, it took us another year to get her back on her feet again. She did it, however.

I would like to show the committee a picture of my daughter at her best. It is a lot nicer. That is how she is. That is how we love to think of her when she is having seizures. I will explain what has happened during her treatment. She has gone through 11 different forms of medication. She began on phenobarbital and she has since gone though Frisium, Topamax, Epilim, stiripentol and many other medications. All of them were unsuccessful in treating her seizures. Some of them were successful for a short period, but the nature of Dravet syndrome is that it breaks through the medication - it makes its way around and the seizures begin again.

We were told 13 months ago that we had come to the conclusion of all the medications that were available to treat Ava's seizures. We were told there was nothing left for her to try other than the ketogenic diet, which is a regulated diet for children with epilepsy that can result in weight loss for some. It is quite severe. Members might be more familiar with it if I were to describe it as something close to a modified Atkins diet. I have been doing a considerable amount of research into medicinal cannabis. Many families in the US have moved to states where medicinal cannabis is available. We did not have access to that here last July, when it became known to me that the Charlotte's Web product, which has been mentioned by Dr. Doherty, was available in England. We were not comfortable with ordering Charlotte's Web online because we did not know exactly where it came from or anything like that. We were told in September that it was available in Dublin, so we decided to travel there. Fortunately for us, we met Joel Stanley, who is one of the producers of Charlotte's Web and is a very nice and ordinary person. He was very willing to talk. After discussing Ava's situation with him, we decided to purchase the Charlotte's Web product. Although we had done a great deal of research, it was very frightening to have this product in my hand. I was very concerned because I wanted to do the best thing for my daughter.

At the end of September, Ava had 23 tonic-clonic seizures in 36 hours. That was the worst bunch of seizures she had had for some time. Things were going in a bad direction for Ava, so we decided to begin to administer Charlotte's Web and see what would happen. After we started the Charlotte's Web treatment, Ava had seven seizures between 2 October and 31 October. I believe that was a reduction of between 80% and 90%. In previous months, Ava could have had seven seizures in two hours. It varied every day. We would not know what to expect from Monday to Tuesday. She might have ten seizures on Monday and two seizures on Tuesday. We experienced just seven seizures last month. This improvement was accompanied by an awakening of the child whom I knew was there the whole time. When Ava was diagnosed, we were told she would never walk or talk and would be in a wheelchair. These were presented as facts in Ava's future. Ava runs rather than walks when she goes to school and she likes to climb. We have to accept that she is not like every other child, but we can see how much she has achieved. Since we have been giving her the CBD oil, there has been an improvement in her awareness. She is now able to do something as simple as getting her shoes. When I ask her to get her shoes, there is a delay but she goes to pick them up. When I ask her to close the door, there is a pause but she does it. She has had little achievements like that. It has been noticed in school that she is more engaged with her peers and other students. She is better able to concentrate on school activities. Ava has improved dramatically on a broad scale, solely as a result of the use of Charlotte's Web.

While this product is completely legal, it is just one component of the marijuana or cannabis plant. We are anxious to get an opportunity to get the help of the doctors. We want the very best for Ava. I have seen in my own home that this is working. I can see that my daughter is standing up straighter. I think it is because she is in less pain. Ava is not non-verbal, but she has very few words. Her speech has been improving since we started to give her this oil. There is more chat and little sentences coming out of her. She is improving. This improvement could be enhanced dramatically if we had access to THC. Overall, we would prefer to be in a position where a doctor could prescribe this product for Ava. That would enable doctors to work with us, rather than being in a sort of grey area. We do not feel we can really talk to our doctor. I cannot say how our doctor feels, but I am sure that if doctors were allowed to prescribe this treatment, they would be able to play a bigger part in Ava's treatment and to help us more. That is what we would like to achieve. We hope the Government will come forward and help us with this.

I thank Ms Twomey for her presentation.

Deputy O'Connell and I are going to the Dáil Chamber to help to make up a quorum.

We will be back in 15 minutes.

I invite the members of the committee to make contributions.

I welcome Ms Twomey and the other witnesses. In the broader context, there is an ongoing debate within the regulatory authority, in society and among clinicians and physicians about the benefits that may arise from the use of cannabinoids to treat epilepsy and other ailments. A Bill relating to this issue will be debated in the Dáil next week. Perhaps that will open up a wider debate in society. I find that when cannabis is mentioned, certain people almost immediately express the view that it is a harmful substance that creates huge difficulties in society. On several occasions during debates with people, I experienced a certain mindset revealing itself when the word "cannabis" was used. Clinicians and regulators might have some knowledge in this area, but how much research is available out there for lay people, politicians and legislators to assess when they are making determinations on the use of these products? I know there can be a lot of division within clinical views, particularly in Ireland. Is an overarching view shared by those involved in the whole area of neurology and, more broadly, in multiple sclerosis and other muscular diseases? Is there still a great deal of division? I suppose that is the key question I am asking.

Ms Twomey has said that she needs a certain type of cannabinoid substance for her daughter, Ava. Are there any other forms of cannabinoids that are beneficial? Is this specifically about THC? Does Ava require very specific types of cannabinoids? Could varying substances within the overall cannabinoid family be beneficial?

How did the family decide on the specific medication that was suitable for their child? Was it the result of trial and error or the outcome of research? Did the clinicians or physicians suggest that this specific drug would be beneficial to Ava?

Ms Vera Twomey

Would the Chairman like me to answer?

Would Dr. Colin Doherty like to address that question?

Dr. Colin Doherty

A great many issues have been raised. I do not think I would characterise the debate in clinical circles as one of division. There is not a great deal of knowledge. The average clinician would not be aware of it because of the way that cannabis treatments have arisen and come through families of carers. That is a little unusual. Let me give an example. A new drug Fycompa has been licensed recently for epilepsy treatment and is being rolled out in various clinics for patients with epilepsy. Fycompa came through the usual scientific circles. It was an investigational product at the level of small scientific laboratories and it was taken up by a drug company which developed it as a product. The drug went through clinical trials.

Patients do not come into the office looking for Fycompa. They ask the doctor about new medicines to treat the condition. It is important to know that while Dravet syndrome, which is the form that Vera's daughter has, is at the top of the pile, we still have 15,000 from the 40,000 people with epilepsy who have not got full control of their epilepsy. About one third of patients do not have full control and a smaller number - several thousand - have very severe epilepsy. We are dealing with patients who ask their doctors if they have anything else to treat their condition. Many have reached the end of the line, just like Vera's daughter has. They have tried everything from ten to 12 different drugs and are not looking for Fycompa. The clinician will go through the data on various drugs and may recommend the patient to try out the drug, having informed the patient of the known side effects, and introduce it slowly.

The cannabinoid drugs have come by a completely different route. Patients are coming into the doctor's surgery, telling him or her that they have researched this drug and they want to know why they cannot have it prescribed for them. It has come to the fore in an unusual way. Patients are walking into doctor's offices and they have more information on the drug than the doctor. That is the simple fact, as Ms Twomey can confirm.

Allowing for the fact there are a small number of highly specialised people in the epilepsy field who know the drug, I would not characterise their feelings about it as one of division. It is simply a question of evidence. It is very important to distinguish between evidence in the generic colloquial term, where there is evidence that something works for this child or that child, and what we call scientific evidence. Scientific evidence should not be open to interpretation. We have established in the western canon of scientific thought that one arrives at scientific evidence by conducting an experiment. Typically in the experiment, one gives the drug to one group of patients and the other group with the same condition get a placebo. We follow the two groups of patients. The groups have to be large enough to be able to draw conclusions. One cannot just give the drug to two people, with two others getting the placebo. In an experiment, there are several hundred people in each wing and at the end of a period, usually 12 to 24 weeks, one establishes whether the drug has worked or not. That is scientific evidence. What we need to have is clear scientific evidence that the drug works.

What we know at this time about cannabis is that there is a purified form of CBD oil made by a small pharmaceutical company called GW Pharmaceuticals. This CBD oil is not a scheduled drug in this country, and although it has passed several layers of evidence, it has not quite reached the level that most doctors would be happy to prescribe it. Once the two placebo controlled trials are published, which will be any time in the next three to four months and if the company then submits the drug for regulatory approval, that is usually the point at which people will say they are happy to prescribe.

There is no division, but caution. The medical profession needs to say that they need to wait until it reaches such a level, a mark on the wall of significance. I would separate this out from personal use. I have no problem with people making a personal decision to use a drug and feel that using a drug with varying levels of THC is a decision they have made for themselves or for a family member. That is a question for society.

There is a solemn duty on a doctor when prescribing a medicine to ensure that drug is safe and effective. It is a very solemn duty and it cannot be gainsaid by anybody suggesting that the medical profession is naturally conservative. It is naturally conservative but for the right reasons. If we end up giving all various forms of this drug to children and find out in a year's time that it has created some very difficult behavioural or other problem in the children, that reflects on the doctor. It is very important we separate out those two phenomena - somebody making a personal decision of how much they want to give themselves or a child versus what we are asking the medical profession to do. It is not a matter of persuading one or two doctors. We have to bring the whole profession with us. As Ms Twomey said, the doctor-patient relationship is extremely important. Nobody wins if anything is pushed through and people are being asked to prescribe something they are not comfortable with. There is much more to the treatment, as Ms Twomey will know, than giving a drug. There are support services, rehabilitation, diet and there is a significant amount going on. If we rupture that relationship by forcing a doctor to prescribe something that he or she is not quite comfortable with, people will leave their doctor to go to other doctors who may not have the same level of expertise.

I am very excited about this form of treatment and I think we can use the evidence that exists and in a reasonably short space of time we will come up with the framework and we can all get behind it. If there is a rupture, it will be around forcing people to prescribe something where the scientific evidence does not exist. I am not saying there is no evidence. I am saying the scientific evidence does not exist.

When Dr. Doherty speaks about scientific evidence, he is saying that scientific evidence does not exist that the drug works. Is that correct?

Dr. Colin Doherty

No. For the particular purified CBD oil, there is scientific evidence, but it has not been published in peer-reviewed journals yet. It has not quite reached the point where people are comfortable with it. Everything is pointing towards reaching the level of scientific significance at which most doctors, especially experts in the area, will be happy to prescribe it. I do not know exactly when that will happen. I anticipate within the next year.

Does that evidence also take into account the long-term effects of the drug or is Dr. Doherty concerned about that?

Dr. Colin Doherty

I am concerned about that. Let me refer to some of the newer drugs that have come through the more conventional role. We have been finding that these drugs have behavioural effects that did not come out in the original trials. The usual number of patients that are required to get a drug across the line into the regulatory zone is sometimes between a couple of thousand to 3,000 to 4,000. If something happens in only one in 5,000 children, one will not see that in the original trials. There are a number of examples going back in history, for example, the drug Vigabatrin, which is still used today, was released in 1991 to great acclaim. It was thought it would be a great addition to the treatment of epilepsy. By 1996, it was clear that it was causing blindness in a small number of people. That drug was banned initially, but now it has been reintroduced in very limited circumstances. It took five years to realise that in a small number of people it causes a severe side effect.

The point I am driving at is that my understanding is that there is a whole series of drugs given to children with epilepsy and there is no clear evidence of the long-term side effect of these drugs either. There is a concern about the long-term side effects of the use of CBD oil and THC, but on the other hand there are many drugs being administered that there are no clear outcomes-----

Dr. Colin Doherty

I would not say there are many. It is the most recent ones. Vigabatrin is a good example of a drug where we came across the problem five years after the start. There is a definite concern about that, even with the newer drugs.

At a minimum, one needs to go through several thousand patients treated, using proper observation of those thousands of patients. We can say with Fycompa, this new drug, that we have had several thousand patients but it has only been on the market two years. We are all being very cautious about the use of the drug because we know the stories about vigabatrin and we are keeping a very open mind, but we are dealing with patients who are looking for life-saving treatment. We are constantly aware of that.

Dr. Colin Doherty

What we are arguing for with CBD is to get over the initial line and then we will be in this cautious phase where we will be mindful of problems down the line but where one is balancing the life-saving potential of the drug versus its potential long-term effects. I do that every day of the week. I make that decision. It is a very solemn duty.

I just want to be clear. Dr. Doherty said he is in favour of getting CBD and THC over the line to start using it and then he can monitor it.

Dr. Colin Doherty

I am in favour of getting over a certain level of scientific evidence that my colleagues and I will be happy with, but that will only be the start of the journey for us because then we will be in a phase where we will be observing it and waiting to see if anything happens to people on the drug two or three years down the line. We will always be monitoring that. The game only starts for us when we get over the initial hurdle. What I am saying is we have not got over the initial hurdle yet. The initial hurdle is getting those-----

Yes, the evidence that the authority is looking for that will get it over the initial hurdle is evidence that it works not evidence that it does this, that or the other following long-term use.

Dr. Colin Doherty

No, we are looking for evidence of value first.

That it actually works.

Dr. Colin Doherty

There is initial safety data but again it is on a relatively small number of products. That means even if we have it licensed we will always be watching and waiting, as the parents will be. Ms Twomey is the same. We are always watching and waiting in order to make sure. One could ask what happens if only one in 5,000 children who takes the drug dies. One could say there is a risk of death anyway. That is the choice we are making. That is the choice Ms Twomey is making. The families are making the choice. We consider the risk of death from the condition and the risk of death from the drug. We are always making that judgment.

I expect they carry that risk with the drugs they are being administered at the moment anyway.

Dr. Colin Doherty

I will go back over this and look at the last two or three drugs that we have. We are talking about several thousand patients in the trials. No deaths have been attributed to the drug but there have been deaths during the trials because the patients have very severe epilepsy and epilepsy causes death. None of the drugs has caused death, that we know of but it could do. It could be one in 5,000. Another drug caused liver failure in one in 5,000 patients and the drug was banned after the post-marketing analysis. It took several years to find the drug because it did not happen in the first couple of thousand patients treated.

Does Ms Twomey want to contribute?

Ms Vera Twomey

The reason we went down that road of the CBD was based on research that started initially with Paige Figi and her daughter Charlotte. That child was getting over 300 seizures a day and after the Stanley brothers produced the oil for Charlotte her seizure count went down to three or four a month. Now that little girl is nine years old and she is doing very well. She is doing regular things like riding her bike and playing games.

In some respects there is an absence of reports but there are good reports, including one done by Professor Mike Barnes which is a very important document to read and take notice of because he covers not only epilepsy and Dravet syndrome but multiple sclerosis, cancer and many other ailments that are helped by CBD in combination with THC. There are reports from Israel as well that are very promising and that information is available.

Deputy Kelleher asked who mentioned the different products to us. We did have a conversation with a consultant about a company called Bedrocan in Holland and that is one avenue that seems promising. The company is well researched and its products are made according to manufacturing guidelines. I suppose the evidence is limited. When we went down the CBD route a lot of our research was coming from families but they were families like us that were struggling and that had gone through 11 and 12 different medications and were left with no alternative. We went down the CBD route because as Dr. Doherty said, from the time Ava was four months old we were told that she could pass away from her seizures at any time. She could go into a seizure that could last 30 minutes or two or three hours. One never knows. She might not come out of a seizure and she would be gone from us. When one is put in that situation, in spite of the fact that there might not be a vast amount of information there, when one speaks to families, and when one looks into the issue and does careful research, although the evidence was anecdotal we took it very seriously. The other families were in the same position as we were.

Reference was made to medication and the side effects of CBD. At present, what I have noticed in terms of side effects with Ava on CBD is an increased appetite, which we could badly do with so that she could put on a little bit of weight, better sleep, and a better stance and gait. She has more words coming and she is doing better at school. I genuinely cannot point to a negative. If there was I would tell the committee but from what we have seen there is not. We cannot say in the long term how things will be, but the risk for our daughter who had over 20 seizures in a 24-hour period is so serious that it is a real balancing act. Trying CBD for Ava has been the best thing we have done so far for her.

Deputy Smith asked about the side effects of other medications. We have been on 11 different medications. I wrote down the names earlier. Frisium was one of the medications we were on and it caused problems with Ava's balance. She was on another drug, Rivatril, which is a benzodiazepine. It is a little like a sleeping tablet so one can get quite addicted to that. Ava was on Rivatril previously and came off it. It took over 12 months for us to wean her off it because it is so potent one has to reduce it by the tiniest degree, three or four weeks at a time. It takes a long time to come down off it because the drug is so addictive.

Topamax is another drug which caused significant speech delay for Ava. We were working really hard to help her with her speech and while the Topamax was helping at the time to control her seizures we did not realise until afterwards that it was affecting her speech. The efforts we were making were being hampered by the medication she was on to stop her seizures.

Keppra is another medication that Ava is on at the moment. Fortunately for us she is not on a huge dose of Keppra but patients that are on a high dose sometimes encounter an effect known as "Keppra rage" where people get very upset, emotional and angry. It is hard to calm such a person down and that is proven to be associated with Keppra. Thankfully, we have not experienced that ourselves but Ava was on another drug which was brought in for her from England when she was about two and a half called Stiripentol. That has been shown to be of significant benefit to a lot of people with Dravet syndrome.

Unfortunately for us, however, Ava was in a coma for a week having been on the medication and subsequently lost the ability to walk when she was approximately two and a half years of age. There are drugs that are available but which have had a very negative effect on us.

As Dr. Doherty mentioned, we are always watching. Even though things are now going well, it is difficult to relax and get used to Ava not having seizures. That is very new for us in the past six weeks or so. She has to be monitored all the time and we have to take great care because there is a serious risk that she will pass away from a seizure. I cannot recall the exact date, but she had a bad seizure at or about the beginning of November and I believe firmly we could have been in serious trouble. The seizure was violent and its power rose her high off the bed. It took her and she lay down; it took her again and she fell. Anyone who has seen an epileptic seizure will understand what I am saying. Had we not had the break in October, when she had just seven seizures, we would have been in real danger of losing our daughter. The cannabidiol, CBD, helped her to fight off the seizure she had at the beginning of November and she is still with us.

I thank Ms Twomey. I call Dr. Breslin.

Dr. Elaine Breslin

I just wanted to comment-----

I apologise but a vote has just been called in the Dáil. We will have to suspend the sitting for 15 minutes.

Sitting suspended at 10.25 a.m. and resumed at 10.40 a.m.

I invite Dr. Nolan to contribute.

Dr. Lorraine Nolan

I will respond to a couple of points. Deputy Kelleher spoke of the mindset towards cannabis, which comes from its history and the fact that it has always been viewed by regulators as a substance of abuse. There are, however, authorised medicines which contain cannabis such as Sativex and a range of synthetic cannabinoid products. This shows the flexibilities among regulators who recognise that they have therapeutic value and that, once there is sufficient scientific evidence, a product can be authorised as a medicine and viewed as part of conventional therapy. Dr. Doherty said the issue was one of evidence and it is a lack of evidence, rather than division, which is the underlying factor. We echo that and while we recognise that there is emerging evidence from research on a range of cannabis-type products many reviews, such as the Barnes report and the Cochrane reviews, cite the limitations within that emerging evidence. The Barnes report, which is cautious and balanced, puts forward strong evidence in favour of the use of cannabis for neuropathic pain, spasms associated with multiple sclerosis and nausea control but found that, in other cases, the evidence was moderate or poor. It also cites limitations in the studies which have been conducted in that they involved small numbers of patients, were not peer reviewed and included controlled populations. We are getting there but we are not there yet in terms of having the evidence to authorise them as medicines.

Other jurisdictions have introduced frameworks to allow access to cannabis for medicinal purposes, but all of these have been demand led and are part of drugs legislation in those countries. Access has been allowed by a relaxation of drug laws so they sit outside what is considered conventional medicine. The focus is on ensuring a controlled supply source that is regulated, particularly in the case of cannabis material, the purity and content of whose cannabinoid components can be controlled. In this way the chemical content, such as the amount of THC and CBD, is known and standardised. The focus has not been on a level of quality control which one would accept from a conventional medicine, though elements of quality control have been put into the system to give reassurance on the quality of the dried cannabis.

Deputy Smith said that side effects were associated with conventional medicines, such as those used to treat epilepsy, and that is a fact but an authorised medicine has been through a rigorous scientific evaluation. All medicines carry risks and all medicines can have side effects. Our job in assessing medicines is to monitor those risks, weigh them against the benefits and ensure the profile is positive in favour of the benefit. The side effects of an authorised medicine are identified during its development. The risks are known and medicines are sold in the market with patient information leaflets showing a product's characteristics. They always list the side effects and say what the expected risks are. Once a medicine is authorised it is subject to a rigorous process whereby the experience of patients is monitored, and things which may not have been anticipated are reported to competent authorities, properly investigated and addressed by regulators. It may be that extra controls are applied or the supply restricted when they are not suitable for full populations. A rigorous system is in place for conventional medicines and they have a full benefit-risk assessment. The risks associated with their use are known and anticipated. We equip our health care professionals to monitor them and, where side effects or new signals arise, they can be reported to an authority and be appropriately investigated.

A point was made about the importance of the best interests of patients and nobody in this room would disagree that the best treatment option for a patient is an authorised medicine. In the absence of the availability of an authorised medicine, or one authorised in another jurisdiction and on which an assessment has been carried out by a regulatory authority, the next best option is access through a clinical trial. There is an appropriate level of regulatory oversight of these mechanisms but there is a limit to the number of cannabis products which are available to meet these needs. They are investigational products although some, as Dr. Doherty pointed out in the case of Epidiolex, are more advanced and there is more evidence with which to work.

In its review of this area the Health Products Regulatory Authority, HPRA, will weigh up all these factors. It will take into account emerging evidence in a balanced and impartial way which takes into account the risks associated with using cannabis, which is typically used as an adjunct supportive treatment in an established ongoing therapeutic programme for a patient. The review will assess how it can be used and what harms are associated with cannabis. The information we have on the harms comes from illicit use and there are strong links between prolonged and excessive use of cannabis and psychosis and schizophrenia. These things are more prevalent in those who start to use cannabis illicitly at an early age and in people with a susceptibility to mental illness. There have been very limited studies which have monitored the side effects of the medicinal use of cannabis. A meta-analysis by the American Medical Association looked at 80 studies and found side effects or adverse events in 69 of them, though they were not hugely significant, being mainly headaches, nausea and drowsiness.

To assist us in our review we will convene a working group of experts as it is important that we bring on board the clinicians practising in the area. We have already identified a number who have agreed to participate and we would like to involve patients in order that we can bring together all the information and review it in an impartial way to see if it has a benefit and a place in patient treatment. In other jurisdictions which have relaxed drug laws and frameworks, there has always been a detailed upfront review and the Barnes report, of which I spoke earlier, was part of the initiatives taken in the UK to advance this issue.

I read this document 20 minutes ago and found it good. Listening to Dr. Lorraine, however, I was disheartened. What are the terms of reference of the Minister's report? Who is involved and what policy and legislative expertise in terms of medicinal cannabis does the HPRA have? The Barnes report, which Dr. Nolan is familiar with, was conclusive on the benefits of medicinal cannabis.

I had very little knowledge of medicinal cannabis until eight months ago when I met a family from Clondalkin whose daughter had Dravet syndrome. I met Ms Twomey four or five months ago in Leinster House. The more that I find out about this plant and medicine, the more I am fascinated by its medicinal benefits. In the past five or six months, I have been astounded by the number of people who use cannabis for medicinal purposes. Shockingly, they are criminalised in some ways. They are not the usual suspects. They are ordinary citizens in very difficult circumstances for whom traditional medicine has not worked. Medical cannabis has worked. They should not be stigmatised or criminalised. I hope that the Bill I am proposing next week will open up the debate on medical cannabis. The movement for medical cannabis is unstoppable. Consider what has happened across Europe and the US. It will happen in Ireland.

There are many people in Ms Twomey's situation, in that they are almost drug resistant. I do not know about Ms Twomey, but in the case of the Clondalkin family, some of the drugs that the child has taken for Dravet syndrome are toxic. CBD oil has a major future.

Will Dr. Nolan explain the review and does it have a timeframe? This country is terrible for reviews, with situations dragging out and being put on the long finger. In the immediate term-----

Has somebody got a phone on?

(Interruptions).

Maybe it is mine. Who will be involved in the review?

Dr. Lorraine Nolan

The terms of reference have been given to us by the Minister, who has asked us to review the availability of authorised medicines containing cannabis. He has also asked us to review the status of ongoing clinical research involving cannabis and associated products. He has asked us to review the international experience of the medicinal use of cannabis. On the basis of these factors, he has asked us for our opinion on its use and, depending on whether we view it positively or negatively, our policy advice. These are the terms of reference that we have been given.

The HPRA has expertise in the authorisation of medicines. There are medicines containing cannabis. From that perspective, we have the experience to know what we are looking for. We also have a section that deals directly with the licensing of controlled drugs under the Misuse of Drugs Acts. I have worked in the area of controlled drugs since 2001. As an organisation, we have considerable expertise on this subject. We have many toxicologists, clinicians and specialists in the quality of medicines.

As an organisation, we do not provide health care. We are not engaged in clinical practice. Our role is the authorisation of products. It is from those on the front line in the treatment of patients with these conditions that we need to understand where this sits. For that reason, we have decided to convene a group to assist us.

The Deputy is right, in that patients and the demand that exists need to be heard. Theirs is an important voice in this programme. The changes brought about in other countries have been based on demand. The scientific evidence is where it is and more information will continue to come through, but we need to examine it collectively and properly. A review is necessary because it is the best way for us to protect patients' safety.

The timeline set by the Minister is tight. We have been given until the end of January. Regarding other countries that have examined this issue, the Barnes report took three months to produce. We are conscious of the timeline and the immediacy of the situation and we are committed to working through this as efficiently as possible.

Regarding the committee's composition, we have identified the clinical specialists that we would like to have on it. We have secured the participation of two consultant neurologists, one of whom specialises in childhood epilepsy. We have secured the participation of a palliative care specialist, a pain control specialist and a pharmacist with an extensive background in cannabinoid research, particularly the pharmacology of cannabinoids. We have also secured the participation of a pharmacist who specialises in palliative care and the possible compounding elements of medicine. We also want to involve patients. We are looking into the best way of achieving that. We undertake patient engagement as part of our role and we normally work through the patient associations relating to the major therapeutic areas for which cannabinoids are being investigated. We will look to those associations to assist us with this.

We must be realistic about the group's composition. If it grows too large, it becomes inefficient and unworkable. We need to control the number of participants so that it can work effectively, but the group will involve a large consultation process. We are trying to achieve a mechanism for including as broad a range of expertise as we can to inform us.

I thank Dr. Nolan. Three further Deputies are offering. In the interests of time, we might take their questions together.

I welcome our guests and thank them for their submissions. It has been enlightening to hear of the first-hand experiences of patients and those who are directly involved in addressing the issues presented by same. Like everyone else present, I have seen epileptic seizures in children that were so severe as to be distressing, not only to their parents, but to people who were not accustomed to such situations.

The Minister is anxious to bring this matter to a conclusion and to achieve the best outcome as quickly as possible, but I accept that we should take safety precautions. If we do not, we will knock the process back and the benefits might not quickly accrue to those whom we have in mind. A long time ago, a treatment was authorised and prescribed for hepatitis C. It both worked and did not work.

For some patients, the results have been dramatic. Compared with having no control over a child's situation, a parent or relative will be heavily on the side of trying to avail of the best possible treatment. I am disposed towards this approach, provided that adequate safety precautions are taken and we do not rush the fences by cutting corners and saying that, since everyone else is taking it, it must be good and we will all have a bit of it. We cannot do that when patients' lives are at stake. Consider the health of the nation.

We have had the debate about the various vaccines prior to this and some patients react in a totally different way to others. The question then arises as to whether we have taken the right decision. We have had this conversation before. I was involved in this back in the 1970s, 1980s and 1990s, unfortunately. When one has seen some of the things that can happen, one begins to become a little bit cautious, notwithstanding the beneficial elements of it. I strongly support the availability of cannabinoids provided that all of these safety points can be met.

Deputy Gino Kenny asked some of the questions about the review and the terms of reference. While I agree that there cannot be a large number of experts engaged in the review because it is such a short timeframe, will the authority be accepting submissions from the public in the review or will it be solely the group of experts looking at the wide range of evidence available to date?

Obviously, the Minister will make the policy decision at the end of the process but in terms of the review, will the HPRA merely give him advice? Will that advice contain recommendations? In her opening statement, Dr. Nolan stated, "If the Minister, following receipt of our advice, takes a policy decision to implement a new legal framework for medicinal cannabis, it will require time to develop [and] may require primary legislation". Even when the Minister takes the advice at the end of January, there will still be a considerable period in which the development of the new legal framework will be progressed. Dr. Nolan also stated it may be possible to start administering medicinal cannabis to meet specific needs within the existing framework. While I do not want to pre-empt the outcome of the review, if it is the case that a recommendation is made or policy advice is given to explore this, we must be clear that there is nothing to stop it. It cannot then be put on the long finger; we cannot wait on the Minister to state we need new legislation or a new legal framework. All of that has to take place but in the short term, there will be options available to start administering it. Is that something that will be contained within the recommendations? Will there even be recommendations in the report or will the HPRA solely be giving advice to the Minister?

Has the Deputy a further point he wishes to make?

It will not be a part of the review, but one argument on medicinal cannabis is that if we start legalising cannabis for medicinal purposes, it will have a knock-on effect for illicit use. There is no evidence whatsoever to suggest that. In fact, in all the countries in which medicinal cannabis can be received, there has been either a stagnation or an actual reduction in the illicit use of cannabis. There is absolutely no evidence to suggest there will be an increase in illicit use on foot of legalising cannabis for medicinal purposes.

I thank the witnesses for coming before the committee. I thank especially Ms Vera Twomey for her attendance. I cannot even imagine what it is like to deal with that number of seizures in a day. I have a family member with epilepsy and have only seen a couple of seizures. It is not an overly pleasant experience and it must be very difficult for her.

I am very heartened by the considered approach of the HPRA to this issue. As a community pharmacist by profession, I would almost say that all drugs are bad, in the sense that all drugs have side-effects and that a patient should never take something unless it is absolutely necessary. In light of previous failings of regulation with regard to Thalidomide and the incomplete trials and data of the past, I note that in the case of CBDB, an extremely complex and multi-targeted drug, it is very difficult to quantify potential side-effects when one cannot track exactly the effect of a drug or the response that it elicits within the system. I also make note of the statements regarding already-licensed drugs such as Keppra, Frisium, Rivotril and such products. As this meeting is in public session, it is important to note that children and families are using those medications at this time. I have a duty to state I would not like to see anybody taking those drugs away from their children because of the risk involved. I wish to say that in public session.

I assume that Dr. Doherty thinks that a consultant or medical professional would need to be involved in the titrating up of a dose of cannabis oil or products containing CBG or THC. A medical person should be involved in the titrating up of those drugs and perhaps in the reduction in dosages of other drugs in order that seizure thresholds are not reduced. As a medical person, I would strongly advocate that a medical professional prescriber be involved in all treatment programmes for people.

Following on from Deputy O'Brien's statement about the illicit use and medicinal use of cannabis, it is worth noting that diamorphine, which is heroin, is used in operating theatres all of the time. It comes in a completely different form than the block one sees on the telly when there has been a drugs seizure. When we talk about medicinal cannabis, it is very important to point out that it is a medicinal product in an oil form. It is not a case of doctors writing prescriptions and pharmacists shovelling grass into bags and sending them off with labels on them. It is a completely different concept and it is worth saying that in order that the argument is not put forward that we are legalising cannabis for people to use on the street, at home or wherever.

I wish to bring to the attention of members that a vote has been called in the Dáil. I will stay behind and keep the meeting going.

Deputy O'Connell and I better go.

We can pair with each other.

How long ago was it called? Do we have a few minutes? I would just like to say that I have spoken to the Minister and I believe he is very supportive of this. I also believe that the correct procedures must be followed. We do not want any child or adult to have some sort of catastrophic event. The authority's role is to safeguard the supply of medicines and to regulate them. We depend on that and we must respect that. I believe the Minister is very supportive of this. I understand that it is probably not very helpful to Ms Twomey when she is dealing with a sick child but I believe a shift is taking place and there are many people within my own party who are quite open to this happening. I will support it in whatever way possible. Having said that, I always will be against the quick authorisation or the fast-tracking of anything. We are administering drugs to children and adults and we need to be mindful of the side effects of drugs and the catastrophic effects of the overuse or misuse of drugs. I am sorry that I must leave.

There is one question I would like to ask. With regard to clinical trials on the benefits of cannabinoids, are there sufficient numbers in Ireland to carry out a clinical trial or would it have to be an international clinical trial? The witnesses might now address those questions. Who would like to take the lead?

Dr. Lorraine Nolan

I will start, if I may, and then perhaps Dr. Elaine Breslin will come in at the end in response to the question about clinical trials. A couple of points have been made and I wish to pick up on the point raised by Deputy O'Brien on the legalisation of cannabis. I believe we need to ensure this is a health-led debate about the medicinal use of cannabis from a medical viewpoint and a treatment viewpoint. The recreational use of cannabis is not part of this.

As I understand it, recreational use might be examined by the national drugs strategy next year as well.

I refer to the point Deputy Gino Kenny made on the cannabis Bill. Some provisions in the Bill would remove cannabis and the THC cannabinoids from the misuse of drugs framework, which would have the effect of legalising them from that point of view. The proposals in the Bill are not fitting for something that is really a legislative proposal for medicinal use. I should make that point.

I am heartened by the point Deputy Durkan raised about patient safety, which was echoed by Deputy O'Connell. Our role is to protect patient safety. That is the reason for our existence. That is the reason we are taking an approach that is robust and involves sufficient expert consultation to ensure that if we make a decision to introduce this, based on evidence of patient benefit, it is done safely. We must remember the way this would be used. It is a supportive treatment so if we make that decision, and we cannot pre-empt the outcome of the review, many patients would remain on their conventional therapy, so even the safety issue becomes complex. We must consider how this material, containing in excess of 100 active components, may interact with other medications as well. Those are the types of issues involved, so it is important we give this time and carry out a thorough review.

Deputy Jonathan O'Brien asked what format our advice to the Minister would take. We intend to do this in a robust way. Certainly, there will be a report on the outcome of the findings of the working group, which we will present to the Minister as well.

Will there be recommendations?

Dr. Lorraine Nolan

There will be recommendations in the report. The Minister has asked for that. The Deputy made the valid point that it is up to the Minister to decide whether legislation will be required to enable this and then we begin the process of developing policy, which is long and will add more time. We acknowledge that, and we raised that point in the statement for that reason. It is an important issue. We have had this debate for a long time and the needs of many patients in the State have to be examined within this, so it must be done correctly. The Deputy referred to the point that I emphasised in the opening statement. There is provision within the existing framework which would allow a doctor to prescribe. To my knowledge it has only been used once previously, in the context of a clinical trial authorisation. To look at that previous precedent, it was in a circumstance where the patients were under the supervision of a specialist and the specialist was monitoring those patients and could follow up on their care. Certainly, there is provision there which can be looked at and, as part of the review and the work of the expert group, it would make sense to include that provision and examine it in the context of whether it could be used. The officials in the Department of Health would have a role in that regard as well.

I wish to tease out that point. It was interesting that earlier we were saying that the clinical evidence must reach a certain level. There is a possibility that the clinical evidence might not be published or contained in peer-reviewed journals before the HPRA's review is completed. There could be a scenario where there is a recommendation that we should pursue a new legal policy or framework to provide medicinal cannabis in the future without the clinical reviews being published. Would the witnesses see that as a barrier to any recommendations they might be examining or would they be of the same opinion as Dr. Doherty? If there is policy advice to the Minister that this is something we can provide within the existing framework while we are waiting for a new legal framework to be completed, does Dr. Doherty think that would satisfy physicians in terms of prescribing or would there still be hesitation until it reached that clinical point?

Dr. Colin Doherty

I do not have a one-off answer to that question. To take a step back before answering it specifically, the only important thing from my point of view is to make sure we bring the medical profession along with whatever we decide. For the reasons I articulated earlier, and I know from my conversations with Vera Twomey that she would agree, we must have a solid doctor-patient relationship as we move forward on this. If that breaks down, people will be out on their own looking for other doctors, who perhaps do not have the same expertise, and asking them to prescribe a medicine. There are a relatively small number of specialists in this country who can justifiably call themselves experts in these difficult forms of epilepsy. It is a handful of fewer than ten or 12 specialists. These people must be brought along. For good or ill, that is what it means to be in Ireland because it is a relatively small community.

The question of whether they will be satisfied that there will be an interregnum before the publication of the data in a peer-reviewed journal will be an interesting one. My sense of it is that we can still come up with a framework where people balance the severity of some forms of epilepsy - to be blunt about it, the risk of death - versus the wait for that pinnacle of evidence. They are human beings like everybody else. They will say that perhaps we can consider this in a limited way for these most difficult forms until the evidence goes through. If there was support across all the regulatory groups and all the experts agree, my sense of it is, and I will not state it definitively, that we could probably come up with some way of administering or prescribing the drug before the definitive evidence is across the line. It is not an issue of conflict, but there will be strong voices on both sides of that argument. I do not wish to pre-empt the findings.

Obviously, the lack of that clinical level having been reached in terms of publication would be a consideration in any policy advice the HPRA gives. I presume it would be a factor the authority would have to consider in giving advice to the Minister.

Dr. Lorraine Nolan

Deputy O'Brien is correct. If I can return to the point about the provision that can be used, it is a licensing provision which the Minister can use at his discretion and ultimately it is up to the Minister to decide whether it should be used. I can give a legalistic explanation of it. It is an exemption from prohibition. By virtue of it being an exemption from a prohibition, it is always unique to the individual circumstances of a particular case. That brings me back to what Dr. Colin Doherty said. It might be for some patients given the immediacy and urgency of their needs and lack of alternatives. All the evidence is taken together to make a decision collectively and it may be that in those instances a clinician, and I cannot speak for clinicians, may make the decision that in his or her opinion and judgment, he or she wishes to try this.

The other point is that the review must look at the range of products that exist. Different levels of evidence are being gathered for each. Dr. Colin Doherty spoke about Epidiolex. That is more advanced than others. When one looks at the weight of evidence that exists for some products, it might be the case that the outcome of this review would be that we can make a decision on certain products and on certain indications. That is certainly the case with the frameworks in place in other countries. They do not have a blanket allowance but only allow it for treatment of certain conditions. They look at it in that way where they believe there is enough weight of evidence to allow it. These are all the issues the group will have to examine.

On Deputy Kenny's question about the composition of the group, I omitted to say that a consultant oncologist is also involved in the group.

Perhaps Dr. Breslin will deal with the clinical trials.

Dr. Colin Doherty

I wish to make a separate point later.

Dr. Elaine Breslin

One of the roles of the HPRA is authorising clinical trials. We are aware there are ongoing trials with Epidiolex, which is the CBD enriched standardised product. Dr. Doherty referred to those.

It is likely that trials would not be conducted in Ireland alone but that we would participate in international trials, such as those being conducted by the GW Pharmaceuticals company, and Irish patients and Irish investigators could participate in those trials. Such trials would be authorised by the HPRA for conduct in Ireland. Were those trials to be submitted here, it is likely that this experience would build confidence among investigators and patients. The HPRA would be very open to receiving those trail applications.

Dr. Colin Doherty

I do not want proceedings to close without a discussion on cost. Within the structures of what we are reviewing here, we will have no capability of jurisdiction for stating that this drug should be made available under the long-term illness scheme, which is the main reimbursement scheme for anti-epileptic drugs. People also get it on the medical card, but as there is a charge per medication there, most people choose to get their medicines under the long-term illness scheme. Getting a drug designated for treatment on the LTI scheme is completely separate and is just not covered by this review. We could recommend it, but it would not necessarily move the situation along.

Cost will be a big issue in this. Certain families accessing the high-CPD versions, as Ms Vera Twomey is, have stopped using it because they cannot afford to continue to pay for it. This meeting should not close without an acknowledgement that the cost issue will be significant and just because there is a recommendation on an individual patient basis that a patient should get it, it is not automatic that the HSE will pay for it.

There is a whole process to get a drug listed on the long-term illness scheme. That sometimes can apply even to established drugs that we use. We sometimes use vitamin supplementation for patients with epilepsy and we have trouble getting the Government to reimburse those because it is not defined as an anti-epileptic drug. I do not think there is an answer to that question.

Is it a Government decision?

Dr. Colin Doherty

The HSE has a process on long-term illness drugs and if it is like anything else in the HSE, I presume it will take time. I am conscious of the Deputy's question. We could go hell-for-leather to come up with this framework and finally reach a decision to definitely prescribe it for particular patients, and suddenly find the drug is not affordable because it is going to take a year to get through the approval process for the LTI scheme. I just want to ensure we are all conscious of that.

It has the recommendation.

I am conscious of time. I call Deputy Gino Kenny.

I do not want to pre-empt the conclusion but given that this only affects a tiny number of people, we would lose a major opportunity for people who want to gain access to medical cannabis. We will see what the findings are. Obviously the Bill will be debated next Thursday. There is a groundswell in Ireland and across Europe that medical cannabis is here to stay. It could be of benefit to tens of thousands of people, including those suffering from MS, arthritis, cancer and epilepsy. It just goes on and on.

Dr. Doherty has made a very good point regarding the medical profession. We need to meet half way because if the medical profession does not buy in, it will be slightly difficult. We all have to buy into this - politicians, those who are using it, the medical profession and the HPRA. This will be beneficial for people who want it. The debate about medicinal use versus recreational use is a different debate. We have had a very healthy debate over recent months. We are having the debate about the medicinal effects of cannabis. We will have the other debate another time. The times are changing and Ireland has to get into the mood of the 21st century that medical cannabis is here to stay.

I will allow the penultimate remarks to Deputy Durkan.

I wish to emphasise something that caught my attention. Deputy Gino Kenny is right that we have to move on with the times. We also have to put in place the necessary safeguards to ensure we do not do something wrong. We need to recognise that it has to be prescribed. Of course, cannabis will make someone feel well. Recreational cannabis has been around for years and has made many people feel well. We want to draw a distinct line between that and cannabis for medicinal purposes. We need to be absolutely clear in our heads about that.

I will give the final remarks to Ms Twomey.

Ms Vera Twomey

I wish to respond to a comment by Deputy O'Connell about Frisium and Rivotril. When I mentioned that, I was only speaking on an individual basis. I did not mean to speak about anybody else's circumstances. I was just referring to the experience we had with those medications. The Deputy spoke about making a catastrophic mistake. From our perspective we have only ever wanted to do absolutely everything as perfectly as we possibly can for Ava. Ideally we would have wanted the CBD to be available in conjunction with the doctor from the very beginning. She spoke about doing it carefully; we also very much want to do things carefully. We do not want any kind of radical move made.

At the same time people in our situation, with a child who is dangerously ill, need this as soon as possible but done correctly. We do not have any options left. It is incredibly important for people to realise that we have exhausted every other avenue available to us and we need a solution for Ava as soon as we possibly can. We want it done correctly but we need it as soon as we can possibly avail of it.

On behalf of the committee, I thank Dr. Nolan, Dr. Breslin, Dr. Doherty and Ms Twomey for appearing before the committee.

On the basis of this engagement, the committee proposes to prepare a report. We may have further engagement. We will make a copy of the report and its recommendations available to the Minister for Health. Is that agreed? Agreed.

The joint committee adjourned at 11.28 a.m. until 1.30 p.m. on Wednesday, 30 November 2016.