doi:10.1111/jpc.12877
Accepted for publication 17 February 2015.
Cannabis has been considered a therapeutic herb by many civilizations across several centuries. During recent months, there has been increasing media interest and public discussion regarding a potential utility for cannabis in paediatric epilepsy. A ground-swell of interest arose largely due to a highly publicised case regarding Charlotte Figi from Colorado.1 Charlotte was a 5-year-old girl with a diagnosis of Dravet syndrome who was experiencing convulsive seizures every 30 min. Her parents sourced a liquid cannabis solution, and within one week of treatment, her seizures had ceased. This story gave rise to newspaper stories, television interviews and documentaries that have circulated the globe and provided a catalyst for discussion. The cannabis plant which treated Charlotte has now been renamed ‘Charlotte’s Web’ and allegedly remains in high demand in Colorado.Since this time, several other families have come forward and publicly reported beneficial impacts of cannabis-based products in the context of paediatric epilepsy. These cases have received widespread publicity.
Children receiving cannabis for epilepsy are generally taking an oral form of the drug in a concentrated oil or liquid. Cannabis contains several cannabinoids that are thought to play a role in modulating neurotransmitter levels, although the mechanisms are not well understood. There is strong theoretical and experimental evidence from animal studies to suggest that cannabinoids may be effective anticonvulsants.2 The psychoactive component responsible for the recreational high is tetrahydrocannabinol (THC).3 Most cannabis preparations marketed for paediatric patients are purported to have reduced levels of THC, although this claim is not easily validated in settings where the manufacturing is unregulated.4,5
Epilepsy is not a rare disease: the prevalence is approximately 1%. About two-thirds of people affected by epilepsy will become seizure-free on one or two anti-epileptic medications. For children at the severe end of the spectrum, however, epilepsy can be a catastrophic disease. Children with epilepsy syndromes such as Dravet, Lennox-Gastaut and some other genetic epilepsies such as CDKL5 (cyclin-dependent kinase-like 5, a rare X-linked disorder that causes early onset severe epilepsy and neurodevelopmental delay) can have hundreds of seizures daily associated with an epileptic encephalopathy that has profound impacts on development and interaction. Unfortunately, some of these children have epilepsy that remains refractory to medication. To complicate this further, these children frequently require multiple anticonvulsants, resulting in significant adverse effects.
It is the group of parents whose children have severe refractory epilepsy who are reporting the use of cannabinoids or who are asking about this treatment. One study demonstrated that parents treating their children with cannabis have seen their children trial an average of 12 anti-epileptic medications before they reach this stage.6
The term ‘cannabis’ instantly mobilises people’s preconceived attitudes to the recreational use of cannabis. At the outset, it is useful to recognise the division between questions of medical cannabis and the movement to legalise recreational drug use. In our experience, parents who ask about potential use of cannabis for children are not inspired by the prospect of lenient drug laws; both liberal and socially conservative families are asking about medical cannabis. These parents almost always have children with severe refractory epilepsy and are desperate to improve the life of their child.
All cannabis-based medicines are illegal in Australia. Parents wishing to source this for their children are generally finding supplies through word of mouth or online information. Several Australian suppliers openly and in fact passionately advertise their production of medical cannabis; some show an apparent altruistic commitment by providing their formulations free of charge.
As medical professionals, we are expected to transcend the anecdotal rhetoric and seek scientific evidence for any proposed therapy. Unfortunately, evidence is limited. A Cochrane review published in 2013 described four small studies related to cannabis in adults with epilepsy.7 Two studies8,9 suggested cannabis may be better than placebo in reducing seizures; however, the sample sizes were small (15 and 9 patients, respectively) and the longest follow-up was 4.5 months. The remaining two studies found no difference between cannabis and placebo.10,11
A specifically designed clinical trial is now underway. GW Pharmaceuticals, a UK-based company, has developed a cannabis-based product aimed at treating paediatric epilepsy. The drug, Epidiolex, has US Food and Drug Administration (FDA approval) for a limited clinical trial aimed at monitoring safety and tolerability while also assessing outcome. At the time of writing, 23 children, all with severe epilepsy, are currently enrolled in the study.
While scientific evidence is pending, parents are forming their own conclusions on efficacy. An online survey of the parents of 19 children with severe paediatric epilepsy syndromes found 84% of the 19 parents reported a reduction in their child’s seizure frequency while taking cannabis. Complete seizure freedom was achieved in 11%. These outcomes were not validated by any independent medical assessments.
The term ‘cannabis’ instantly mobilises people’s preconceived attitudes to the recreational use of cannabis. At the outset, it is useful to recognise the division between questions of medical cannabis and the movement to legalise recreational drug use. In our experience, parents who ask about potential use of cannabis for children are not inspired by the prospect of lenient drug laws; both liberal and socially conservative families are asking about medical cannabis. These parents almost always have children with severe refractory epilepsy and are desperate to improve the life of their child.
All cannabis-based medicines are illegal in Australia. Parents wishing to source this for their children are generally finding supplies through word of mouth or online information. Several Australian suppliers openly and in fact passionately advertise their production of medical cannabis; some show an apparent altruistic commitment by providing their formulations free of charge.
As medical professionals, we are expected to transcend the anecdotal rhetoric and seek scientific evidence for any proposed therapy. Unfortunately, evidence is limited. A Cochrane review published in 2013 described four small studies related to cannabis in adults with epilepsy.7 Two studies8,9 suggested cannabis may be better than placebo in reducing seizures; however, the sample sizes were small (15 and 9 patients, respectively) and the longest follow-up was 4.5 months. The remaining two studies found no difference between cannabis and placebo.10,11
A specifically designed clinical trial is now underway. GW Pharmaceuticals, a UK-based company, has developed a cannabis-based product aimed at treating paediatric epilepsy. The drug, Epidiolex, has US Food and Drug Administration (FDA approval) for a limited clinical trial aimed at monitoring safety and tolerability while also assessing outcome. At the time of writing, 23 children, all with severe epilepsy, are currently enrolled in the study.
While scientific evidence is pending, parents are forming their own conclusions on efficacy. An online survey of the parents of 19 children with severe paediatric epilepsy syndromes found 84% of the 19 parents reported a reduction in their child’s seizure frequency while taking cannabis. Complete seizure freedom was achieved in 11%. These outcomes were not validated by any independent medical assessments.
There are several challenges faced by neurologists and paediatricians whose patients are taking cannabis-based products, the most obvious being the legal status of the therapy. The second is lack of data regarding safety and adverse effects in children. While there are clear benefits to controlling refractory epilepsy, there are no data about the potential for long-term neuro-behavioural consequences in children treated with cannabinoids.
The lack of standardized manufacturing and absence of regulation only amplifies these concerns. While the safest medico-legal stance may be ‘don’t ask, don’t tell’, this removes an important safety mechanism for the patient. If we are unaware of what our patients are taking, there is a potential risk for interactions with other medications. Moreover, if there are potential side effects associated with cannabinoid use, it is in the child’s best interest to have regular medical reviews. This is only possible in an open and non-judgemental environment.
The challenges are multiplied if a child taking cannabis is admitted to an Australian hospital, particularly if the cannabis is thought to be beneficial in the eyes of the parents and/or clinician. Hospitals are not generally willing to permit staff to prescribe or administer cannabis or even have the substance stored on premises. However, if cannabis is proving to be an effective anti-epileptic medication for the child, then withholding the medication may be medically and ethically problematic. If so, an ethical case can be made for permitting parental administration of cannabinoids, as is often the case with complementary medicines in hospital.
Currently, when parents whose children are affected by severe epilepsy ask about cannabis as an option, there are several issues to consider. Parents need to know that the medication is illegal and, as doctors, we cannot prescribe or promote its usage. We need to acknowledge that their sense of desperation to improve life for their child is valid. If parents feel we are dismissing the validity of their question, they are less likely to share further concerns or to divulge if they are treating their child with cannabis. We need to be clear that currently there is no form of medical cannabis in Australia that has been tested or standardised and we are uncertain about side effects or interactions because the information has not yet been gathered. With the recent announcement by the NSW Premier of a trial of cannabinoids in refractory epilepsy, we can provide reassurance that better medical information about the role of cannabinoids in refractory epilepsy will be available.
Typically, the development of a new medication for epilepsy is associated with the publication of scientific data that allows clinicians to assess the risk : benefit ratio and then decide who should be treated. This paradigm has been reversed almost entirely by the publicity given to medical cannabis and the fact that parents are choosing to administer it.
The lack of standardized manufacturing and absence of regulation only amplifies these concerns. While the safest medico-legal stance may be ‘don’t ask, don’t tell’, this removes an important safety mechanism for the patient. If we are unaware of what our patients are taking, there is a potential risk for interactions with other medications. Moreover, if there are potential side effects associated with cannabinoid use, it is in the child’s best interest to have regular medical reviews. This is only possible in an open and non-judgemental environment.
The challenges are multiplied if a child taking cannabis is admitted to an Australian hospital, particularly if the cannabis is thought to be beneficial in the eyes of the parents and/or clinician. Hospitals are not generally willing to permit staff to prescribe or administer cannabis or even have the substance stored on premises. However, if cannabis is proving to be an effective anti-epileptic medication for the child, then withholding the medication may be medically and ethically problematic. If so, an ethical case can be made for permitting parental administration of cannabinoids, as is often the case with complementary medicines in hospital.
Currently, when parents whose children are affected by severe epilepsy ask about cannabis as an option, there are several issues to consider. Parents need to know that the medication is illegal and, as doctors, we cannot prescribe or promote its usage. We need to acknowledge that their sense of desperation to improve life for their child is valid. If parents feel we are dismissing the validity of their question, they are less likely to share further concerns or to divulge if they are treating their child with cannabis. We need to be clear that currently there is no form of medical cannabis in Australia that has been tested or standardised and we are uncertain about side effects or interactions because the information has not yet been gathered. With the recent announcement by the NSW Premier of a trial of cannabinoids in refractory epilepsy, we can provide reassurance that better medical information about the role of cannabinoids in refractory epilepsy will be available.
Typically, the development of a new medication for epilepsy is associated with the publication of scientific data that allows clinicians to assess the risk : benefit ratio and then decide who should be treated. This paradigm has been reversed almost entirely by the publicity given to medical cannabis and the fact that parents are choosing to administer it.
It is hoped that the current and pending medical trials will enable practitioners to evaluate the role of cannabis in treating epilepsy. They may also provide an impetus for legal reform if that is what is required. In the meantime, we can expect parents to continue seeking out and administering cannabis as a treatment when they believe no other options are available. In terms of assessing whether this is reasonable, some useful questions to ask include: Does this child have severe epilepsy that is proving refractory to other medications? Are the parents acting in the best interest of their child and are they informed about the uncertainty surrounding this therapy? Are you able to see the child for regular reviews and are you satisfied there has been no deterioration since cannabis was commenced? If these questions can be answered affirmatively, then it is difficult to argue for undermining parental autonomy. As doctors we have a responsibility to be open and to use our skills in counselling and critical analysis to help parents address these very difficult questions.
References
1 Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014; 55: 783–6.
2 Devinsky O, Cilio MR, Cross H et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014; 55: 791–802.
3 Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia 2014; 55: 787–90.
4 Leach JP, Mohanraj R, Borland W. Alcohol and drugs in epilepsy: pathophysiology, presentation, possibilities, and prevention. Epilepsia 2012; 53 (Suppl. 4): 48–57.
5 Gordon E, Devinsky O. Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia 2001; 42: 1266–72.
6 Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013; 29: 574–7.
7 Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst. Rev. 2012; 6: CD009270.
8 Cunha JM, Carlini EA, Pereira AE et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980; 21: 175–85.
9 Mechoulam R, Carlini EA. Toward drugs derived from cannabis. Naturwissenschaften 1978; 65: 174–9.
10 Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. S. Afr. Med. J. 1986; 69: 14.
11 Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. Marijuana ’90 International Conference on Cannabis and Cannabinoids; 8–11 July 1990, Kolymbari, Crete: International Association for Cannabinoid Medicines, 1990; Section 2, p. 5.
1 Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014; 55: 783–6.
2 Devinsky O, Cilio MR, Cross H et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014; 55: 791–802.
3 Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia 2014; 55: 787–90.
4 Leach JP, Mohanraj R, Borland W. Alcohol and drugs in epilepsy: pathophysiology, presentation, possibilities, and prevention. Epilepsia 2012; 53 (Suppl. 4): 48–57.
5 Gordon E, Devinsky O. Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia 2001; 42: 1266–72.
6 Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013; 29: 574–7.
7 Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst. Rev. 2012; 6: CD009270.
8 Cunha JM, Carlini EA, Pereira AE et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980; 21: 175–85.
9 Mechoulam R, Carlini EA. Toward drugs derived from cannabis. Naturwissenschaften 1978; 65: 174–9.
10 Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. S. Afr. Med. J. 1986; 69: 14.
11 Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. Marijuana ’90 International Conference on Cannabis and Cannabinoids; 8–11 July 1990, Kolymbari, Crete: International Association for Cannabinoid Medicines, 1990; Section 2, p. 5.
Journal of Paediatrics and Child Health 51 (2015) 476–477
© 2015 The Authors
Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
© 2015 The Authors
Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
477
