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The green leaves of recovery

Epilepsy
Alex Turnbull examines the likelihood that the UK will see a revolution in cannabis-based medicine

The use of cannabis recreationally has long been regarded with wariness by the medical establishment, it is increasingly being seen as a valuable treatment for many conditions, such as epilepsy.

In the US, 33 states have approved the medical use of cannabis, although the overall legal status remains complex. But in the UK, clinical trials may soon begin, after the campaigning work of Charlotte Caldwell, mother of Billy Caldwell, a 12 year old boy with severe epilepsy.

Ms Caldwell tried to obtain medical cannabis in the UK but was denied, so she took him to the US and Canada to seek treatment. This was remarkably successful. With CBD Billy’s seizures reduced hugely, and with the addition of full extract cannabis oil they disappeared completely. He was able to stop his other medications, and his cognitive and motor abilities markedly improved.

When his mother returned home to Northern Ireland Billy’s GP he agreed to prescribe the cannabis oil. But when the Home Office found out the GP was threatened with a charge of gross medical misconduct if he continued to prescribe an illegal drug, so he stopped.

To prevent Billy’s condition deteriorating, his mother took him back to Canada for more supplies and tried to import them into the UK, declaring them at Heathrow airport customs. The drugs were confiscated, and Caldwell’s condition rapidly worsened. However, in July 2018, the government relented, and allowed the prescription of cannabis by specialist medical professionals from 1 November.

Now, after a recent meeting with Professor Helen Cross, Consultant in Paediatric Neurology at Great Ormond Street Hospital, Ms Caldwell claims that talks to begin clinical trials for the prescription of cannabinoid medicines are underway.

‘A planned UK Clinical trial means other children could be given the chance to see if medicinal cannabis works for them,’ said Ms Caldwell. ‘The end result we hope is NHS prescriptions for this amazing plant based medicine and no need for private and expensive prescriptions.’

‘We consider only purified cannabidiol for patients with very difficult to treat epilepsy, who are not candidates for epilepsy surgery, vagus nerve stimulation treatment or the ketogenic diet,’ said a spokesperson for Great Ormond Street Hospital. ‘Currently we are awaiting further guidance from NICE and NHS England that will address questions of funding and prescription for patients. In general, purified cannabidiol is not available for prescription apart from in a very few limited cases where expert clinicians deem it suitable.’

Medical usage

The medical use of preparations derived from the cannabis sativa plant has a long history.

There is evidence of use from 3000 year old tombs in Egypt and Siberia. It had a place in Indian and Chinese medical writing from nearly as long ago, where it was used as an anaesthetic (the Mandarin term for anaesthesia literally means cannabis intoxication).

It didn’t enter the UK until the late 1600s, but by the 1800s it was widely used, sold over the counter as an alcoholic tincture for problems such as tetanus and seizures. Its efficacy more broadly became apparent, and the definitive overview was published in The Lancet in 1890 by John Russell Reynolds. It is believed that Queen Victoria used cannabis medicines, particularly for period and childbirth pains.

However, by the 20th century, medical use of cannabis had largely declined. Its consumption for medical purposes was already very limited when in 1961 cannabis was included in the United Nations Single Convention on Narcotic Drugs and classified as a drug that had no medical uses.

In the past 20 years, however, there has been a resurgence of patient interest in using cannabis and cannabinoids to treat a variety of conditions, including chronic pain, cancer pain, depression, anxiety disorders, sleep disturbances and neurological disorders, the symptoms of which are reportedly improved by using cannabis.

Currently, very few people in the UK are likely to get a prescription for medical cannabis.

It is only likely to be prescribed for children and adults with rare, severe forms of epilepsy, and adults with vomiting or nausea caused by chemotherapy.

‘With regard to UK legislation it IS probably sufficient for the few cases where medicinal cannabis has some evidence for its clinical effectiveness however many patient groups would like to see legislation extended to cover more patients with MS and for a broader range of practitioners to be able to prescribe it. Currently it can only be prescribed by specialists and not by GPs or juniors,’ said Deborah Robertson, lecturer in adult nursing at Salford University, and consultant editor of the Journal of Prescribing Practice.

A 2017 study led by Professor Cross, published in the New England Journal of Medicine, found that cannabidiol, one of 113 cannabinoids in cannabis plantsreduces seizures by nearly 40% in children with a form of drug resistant epilepsy, known as Dravet syndrome. For 5% of patients, seizures stopped completely. The study also suggests that the medicine also has the potential to provide relief to the thousands of children with other strains of epilepsy who live with debilitating seizures. Cannabidiol is a substance discrete from THC, the psychoactive element in cannabis, which has been linked to psychotic episodes

‘The results of this study are significant and provide us with firm evidence of the effectiveness of cannabidiol,’ said Professor Cross. ‘This drug could make a considerable difference to children who are living with Dravet syndrome and currently endure debilitating seizures.’

‘At present, cannabis-derived products can vary greatly in their composition, effectiveness and level of impurity. It is important that clinicians, patients and their families are confident that any prescribed medication is both safe and effective. The Advisory Council on the Misuse of Drugs recommends that an appropriate definition be agreed by Department of Health and Social Care and Medicines and Healthcare Products Regulatory Agency promptly. Only products meeting this standard and definition should be given medicinal status,’ said Chair of the Advisory Council on the Misuse of Drugs, Dr Owen Bowden-Jones.

‘Though we agree with the Chief Medical Officer for England that there is now evidence of therapeutic benefit for some cannabis-derived products in some medical conditions, we are also recommending that urgent clinical trials be carried out to better improve our understanding of these products.’

However, the roll out of medical cannabis has been much slower than patients and parents had hoped. Still only a tiny number of children with severe juvenile epilepsies are being treated, and many others continue to have multiple seizures because neurologists will not prescribe.

‘There are several likely reasons for this,’ said Professor David Nutt, the Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences, at Imperial College, writing in the BMJ ‘One is ignorance of the value of cannabis medicines, because few doctors have any training or experience in this area and are fearful of prescribing them off licence.

‘Another reason for resistance could be that parents and patients lead this initiative rather than the medical profession. Some doctors fear that medical cannabis will lead to severe adverse effects such as psychosis, and others that it will lead to more recreational use, which seems unlikely given the current wide use and availability of black market cannabis. Additionally, some pharmacists and clinical commissioning groups are refusing to pay. Another substantial challenge is obtaining supplies, because currently all medical cannabis has to be sourced from foreign producers in the Netherlands and Canada.’

Doubts

Despite some positive indications, it remains unclear if cannabis base medicine is the magic bullet some think it is. In the past, clinical trials to evaluate the effectiveness of marijuana to treat certain conditions have been restrictive and limited. As medical marijuana becomes more prevalent throughout the world, researchers are doing more studies.

However,according to a study published in Frontiers in Pharmacology,expert reviews of current research continue to advocate that more studies are needed. Many of the hurdles involve controlling the quality and dosing of cannabis with what is legally available to researchers. Additionally, a number of the current studies are not controlled clinical trials in which a placebo or alternative medicine is used. Without more of these comparative studies, scientific evidence on the therapeutic effects of cannabis will remain in question.

While in the case of Billy Caldwell, cannabis based medicine seems to have proven a welcome treatment for his seizures, it remains unclear if we will see regular prescriptions of medical cannabis in the future.