Australian Chapter of the International Bureau for Epilepsy
Position Statement: “Medical marijuana” in the treatment of epilepsy
In this context it is important to distinguish between ‘medical marijuana’ (crude cannabis) and pharmaceutical (synthetic) cannabis. The term ‘medical marijuana’ refers to the unique compounds of the plant Cannabis sativa, called cannabinoids, which may be effective in preventing or reducing seizures. Components that have attracted considerable attention are cannabidiol (CBD), the major nonpsychotropic compound, and tetrahydrocannabinol(THC) the compound that gives cannabis its psychotropic effect, and combinations of these compounds. ‘Medical marijuana’ or crude cannabis is unregulated, and the potency and safety is unknown and variable. It is illegal to supply or be in possession of ‘medical marijuana’ in Australia.
Pharmaceutical or synthetic cannabis is the product of a controlled manufacturing process that mimics or produces similar effects to cannabis and is approved for the treatment of various medical conditions. The pharmaceutical drugs Cesamet and Marinol (synthetic cannabinoids usually used to treat pain and wasting associated with HIV or chemotherapy) are not marketed in Australia but are included on schedule 8 to enable particular patients to access them through the Special Access Scheme (SAS), while Sativex, an oromucosal spray containing cannabinoids, was registered in Australia for use in treating spasticity related to multiple sclerosis, in 2012.2
Research data on the use of ‘medicinal marijuana’ for the treatment of epilepsy is limited.
Basicresearch studies have provided strong evidence for safety and anticonvulsant propertiesof CBD. However, the ‘lack of pure, pharmacologically active compounds and legalrestrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports’. 3 A Cochrane Review published in 2014 on Cannabinoids for Epilepsy reviewed published literature to assess the efficacy and safety of cannabinoids when used as monotherapy or add-on treatment for people with epilepsy found that no reliable conclusions could ‘be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy.’ Only four studies from 1978 to 1990 met the selection criteria of randomized control trials (RCTs) whether blinded or not. Patient numbers were small, 48 in total, with varying reports on reduction in seizure frequency and/or seizure freedom (2 of 4 patients at 3 months, Mechoulam, 1978), and as the studies ran for short periods of time, (4 weeks – 18mths) the safety of long term cannabidiol treatment cannot be reliably assessed.4
The American Academy of Neurology conducted a systematic review of the efficacy and safety of medical marijuana in selected neurological disorders, found that the use of oral cannabinoids are of unknown efficacy in epilepsy, that the risks and benefits of medical marijuana should be weighed carefully, and that the comparative effectiveness of medical marijuana vs other therapies is unknown for epilepsy. 5
In the United States, the Food and Drug Agency has given Orphan Drug Status to Epidiolex (cannabidiol) as an investigational drug therapy of Dravet and Lennox-Gastaut syndromes. There is an ongoing open label study, i.e. a clinical research study in which the participant, health care professional, and others know the drug and dose being given, that has recently released data for 27 patients treated for more than 12 weeks.6 Four patients were seizure free and approximately half the patients had a 50% reduction in seizures. Somnolence, fatigue, diarrhoea and altered appetite were each seen in more than 10% of these patients. These interim results look positive and we wait for further results to be published.
How can we improve the current situation? We need to be able to use information from well-conducted clinical trials of these treatments, just the same as any other new treatment. Trials are currently in progress. These will provide good quality evidence and if ‘medical marijuana’ is found to be beneficial, allow best practice guidelines to be developed in the treatment of severe epilepsy. At the moment that information just isn’t available. We need to recognise there is uncertainty around the efficacy and safety of using ‘medical marijuana’ in children and the potential impact it can have on the developing brain in regard to memory, cognition, and the potential for psychosis in later years. Patients and families need to give careful consideration to such issues. If this alternative treatment is commenced, it is advisable to inform the treating doctor so that if a significant change in the patient’s health occurs this can be more completely assessed. It also important to understand that if this alternative therapy is commenced and the person requires future hospitalization, the therapy will be discontinued during this time.
There is a lot of excitement about these therapies, but at the moment we need to be cautious and look carefully at the new information coming out of trials before we can give these treatments unqualified endorsement. Patients and families need to keep in mind that Epilepsy Associations, hospitals and doctors can’t legally provide or recommend these treatments at the current time.
The Joint Epilepsy Council of Australia understands the medical complexity of epilepsy and the difficult decisions facing people with epilepsy and their families. The Council urges all people living with epilepsy to consult with an epilepsy specialist and explore the many existing treatment options, so that they can make informed decisions with their specialist that weighs the risks and benefits of the different treatment options.
Until such time ‘medical marijuana’ is approved by the Therapeutic Goods Administration as an adjunct treatment in the management of severe refractory seizures or catastrophic epilepsy syndromes with clear guidelines and indications for its use and recommended doses, the Joint Epilepsy Council of Australia cannot endorse the illegal use of this substance.
Orphan drug status is given to drugs which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the US, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.