Cannabis Oil Shows Promise as Treatment for Untreatable Childhood Epilepsy
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The development of improved anti-epilepsy and anticonvulsant drugs over recent years has given many epilepsy sufferers a way to control their seizures, allowing them to lead normal, high-functioning lives. Despite the variety of epilepsy drugs available, up to 30% of people with epilepsy are resistant to the effects of anti-epileptic drugs, and as a result, continue to experience seizures. Epilepsy patients who experience uncontrolled seizures often feel at the mercy of their condition and fear having seizures in potentially risky scenarios, such as while swimming or crossing a busy road. As a result, epilepsy sufferers also have a higher risk of developing anxiety than the general population.
There are many different types of epileptic seizures, each with their own symptoms, and each with a different likelihood of responding positively to drug treatment. One of the most resistant types of epilepsy to traditional therapeutic drugs is Dravet syndrome.
The effects of Dravet syndrome
Dravet syndrome is a rare genetic brain dysfunction. It begins in infancy, usually when a child is between 1-18 months old and is a lifelong condition. It is often misdiagnosed in infancy as the child will be otherwise completely healthy, and the traditional ways of diagnosing epilepsy using magnetic resonance imaging (MRI) or electroencephalogram (EEG) tests struggle to detect the early signs of the syndrome. In most cases, the development of Dravet syndrome can be linked to a de novo mutation of the sodium channel gene SCN1A in the child.
People with Dravet syndrome often experience different symptoms as they age. The first seizures are usually generalized tonic-clonic seizures where the patient loses consciousness, potentially falling over if they were standing. They may also appear to convulse as their muscles tighten and relax rapidly due to abnormal electrical activity in the brain. As they get older, the patient may also experience myoclonic seizures, where their consciousness is retained but they experience rapid involuntary muscle jerks.
In addition to the epileptic seizures, Dravet syndrome patients usually experience developmental delays, as such it is common for them to develop speech impairments, low muscle tone, irregular walking gaits, and a general lack of coordination or dexterity as a result of their condition. With patients’ quality of life affected so much by this condition, the benefits of finding an effective anti-epilepsy drug for Dravet syndrome is near-immeasurable for those affected.
Researchers spurred on by the observed potential of cannabis oils in the treatment of other types of epilepsy, have been turning their attention towards similar cannabis-based therapeutics for the treatment of Dravet syndrome.
A joint research effort between two Canadian institutions, the Hospital for Sick Children and the University of Toronto, recently unveiled the results of their landmark open-label trial for the use of cannabidiol (CBD)/tetrahydrocannabinol (THC) cannabis oil in minors with Dravet syndrome. Previous studies on children with various types of epilepsy have focused on CBD-only formulations of cannabis oil. The Canadian researchers hoped that the inclusion of small amounts of THC in the cannabis oil used in their study could help in mitigating some of the negative side effects observed in the CBD-only trials. As a result, the study became dual-purpose, with the aim of both assessing the effects of the cannabis oil on quality of life, and to establish the dosing and tolerability of the cannabis oil.
Dosing and tolerability of CBD/THC cannabis Oil
The cannabis oil used in this study was TIL-TC150, produced by Tilray. It has CBD and THC present in a 50:1 ratio, so it wasn’t expected that any of the psychotropic effects usually associated with THC would be observed in the children.
Twenty children with Dravet syndrome were involved in the study. The effect of the cannabis oil on their seizure frequency and quality of life was monitored through seizure diaries, quality of life questionnaires, ambulatory EEGs, and blood sampling. Dosages started from small amounts of the test drug, initially 2 mg/kg/day CBD (0.04 mg/kg/day THC) all the way up to the nominal target dose of 16 mg/kg/day of CBD (0.32 mg/kg/day THC) over the course of a 20-week intervention period. Sadly, one of the children died from sudden unexpected death in epilepsy (SUDEP) over the course of this 20-week period, but this was not as a result of the study.
Of the 19 children who completed the 20-week intervention period, 8 managed to achieve the target dose. The remaining 11 stopped at doses ranging from 7-14 mg/kg/day as a result of unpleasant side effects such as somnolence/fatigue (81% affected), anorexia (54.5%), diarrhea (36%), and weight loss (36%), but it should be noted that no psychoactive side effects were noticed. The blood work revealed that roughly half of the children had elevated liver enzyme levels and a slightly reduced platelet count, though without the presence of any pre-existing liver conditions these levels are not dangerous.
A statistical analysis of the reported side effects concluded that the increasing rates of reported somnolence were the only statistically significant (P < 0.05) adverse event, and as the intervention period continued the reported rates of somnolence decreased significantly over time. While the other side effects may not be statistically significant, given the potential health risks that conditions like anorexia present, the researchers recommend that patients receiving cannabis oil therapy should be closely monitored when going through changes to their dosage.
Importantly, despite a majority of participants not being able to achieve the nominal target dosage due to side effects, no participants chose to withdraw from the study and all were willing to remain at their individual most tolerable dosage for the remainder of the 20-week period. Additionally, 14 of the 19 participants chose to continue into a longitudinal maintenance study after the 20-week intervention period was complete.
The effectiveness of cannabis oil as an anti-epileptic drug
The willingness to continue in the study is a testament to the effectiveness of the cannabis oil. A comparison between the start and end of the 20-week study period showed a statistically significant reduction of 70.6% in seizure frequency. The number of days with myoclonic motor jerks also decreased, from an average of 5 days per week to 0.5 days per week. Two participants in the study even became completely seizure free over the course of the study.
Quality of life questionnaires conducted at different points during the 20-week period also showed marked improvement. A statistically significant reduction in maladaptive behavior was reported by the parents and caregivers of the children in the study. An increase was also observed in the overall quality of life which was measured across a range of variables, including cognition, general health, behavior, and social activity.
Importantly, the effectiveness of the cannabis oil therapy did appear to be tied to the dosage, as the group who reached the target dose also experienced the greatest reduction in seizure frequency when compared to their condition at the start of the study.
Future recommendations
The authors believe this study is strong evidence that CBD/THC cannabis oil can bring about a significant improvement in the lives of children with Dravet syndrome, with manageable side effects. The study also provides a wealth of information surrounding commonly tolerable dosages, and the varying benefits at different dosage levels, which is important information to have if CBD/THC cannabis oil is to become a common therapeutic for treating drug-resistant epilepsy.
In terms of future research, the authors do note that researching the potential impact of the “entourage effect” between a wider range of cannabinoids and terpenes could lead to the creation of medicinal cannabis oils with fewer side effects.
There are many different types of epileptic seizures, each with their own symptoms, and each with a different likelihood of responding positively to drug treatment. One of the most resistant types of epilepsy to traditional therapeutic drugs is Dravet syndrome.
The effects of Dravet syndrome
Dravet syndrome is a rare genetic brain dysfunction. It begins in infancy, usually when a child is between 1-18 months old and is a lifelong condition. It is often misdiagnosed in infancy as the child will be otherwise completely healthy, and the traditional ways of diagnosing epilepsy using magnetic resonance imaging (MRI) or electroencephalogram (EEG) tests struggle to detect the early signs of the syndrome. In most cases, the development of Dravet syndrome can be linked to a de novo mutation of the sodium channel gene SCN1A in the child.
People with Dravet syndrome often experience different symptoms as they age. The first seizures are usually generalized tonic-clonic seizures where the patient loses consciousness, potentially falling over if they were standing. They may also appear to convulse as their muscles tighten and relax rapidly due to abnormal electrical activity in the brain. As they get older, the patient may also experience myoclonic seizures, where their consciousness is retained but they experience rapid involuntary muscle jerks.
In addition to the epileptic seizures, Dravet syndrome patients usually experience developmental delays, as such it is common for them to develop speech impairments, low muscle tone, irregular walking gaits, and a general lack of coordination or dexterity as a result of their condition. With patients’ quality of life affected so much by this condition, the benefits of finding an effective anti-epilepsy drug for Dravet syndrome is near-immeasurable for those affected.
Researchers spurred on by the observed potential of cannabis oils in the treatment of other types of epilepsy, have been turning their attention towards similar cannabis-based therapeutics for the treatment of Dravet syndrome.
A joint research effort between two Canadian institutions, the Hospital for Sick Children and the University of Toronto, recently unveiled the results of their landmark open-label trial for the use of cannabidiol (CBD)/tetrahydrocannabinol (THC) cannabis oil in minors with Dravet syndrome. Previous studies on children with various types of epilepsy have focused on CBD-only formulations of cannabis oil. The Canadian researchers hoped that the inclusion of small amounts of THC in the cannabis oil used in their study could help in mitigating some of the negative side effects observed in the CBD-only trials. As a result, the study became dual-purpose, with the aim of both assessing the effects of the cannabis oil on quality of life, and to establish the dosing and tolerability of the cannabis oil.
Dosing and tolerability of CBD/THC cannabis Oil
The cannabis oil used in this study was TIL-TC150, produced by Tilray. It has CBD and THC present in a 50:1 ratio, so it wasn’t expected that any of the psychotropic effects usually associated with THC would be observed in the children.
Twenty children with Dravet syndrome were involved in the study. The effect of the cannabis oil on their seizure frequency and quality of life was monitored through seizure diaries, quality of life questionnaires, ambulatory EEGs, and blood sampling. Dosages started from small amounts of the test drug, initially 2 mg/kg/day CBD (0.04 mg/kg/day THC) all the way up to the nominal target dose of 16 mg/kg/day of CBD (0.32 mg/kg/day THC) over the course of a 20-week intervention period. Sadly, one of the children died from sudden unexpected death in epilepsy (SUDEP) over the course of this 20-week period, but this was not as a result of the study.
Of the 19 children who completed the 20-week intervention period, 8 managed to achieve the target dose. The remaining 11 stopped at doses ranging from 7-14 mg/kg/day as a result of unpleasant side effects such as somnolence/fatigue (81% affected), anorexia (54.5%), diarrhea (36%), and weight loss (36%), but it should be noted that no psychoactive side effects were noticed. The blood work revealed that roughly half of the children had elevated liver enzyme levels and a slightly reduced platelet count, though without the presence of any pre-existing liver conditions these levels are not dangerous.
A statistical analysis of the reported side effects concluded that the increasing rates of reported somnolence were the only statistically significant (P < 0.05) adverse event, and as the intervention period continued the reported rates of somnolence decreased significantly over time. While the other side effects may not be statistically significant, given the potential health risks that conditions like anorexia present, the researchers recommend that patients receiving cannabis oil therapy should be closely monitored when going through changes to their dosage.
Importantly, despite a majority of participants not being able to achieve the nominal target dosage due to side effects, no participants chose to withdraw from the study and all were willing to remain at their individual most tolerable dosage for the remainder of the 20-week period. Additionally, 14 of the 19 participants chose to continue into a longitudinal maintenance study after the 20-week intervention period was complete.
The effectiveness of cannabis oil as an anti-epileptic drug
The willingness to continue in the study is a testament to the effectiveness of the cannabis oil. A comparison between the start and end of the 20-week study period showed a statistically significant reduction of 70.6% in seizure frequency. The number of days with myoclonic motor jerks also decreased, from an average of 5 days per week to 0.5 days per week. Two participants in the study even became completely seizure free over the course of the study.
Quality of life questionnaires conducted at different points during the 20-week period also showed marked improvement. A statistically significant reduction in maladaptive behavior was reported by the parents and caregivers of the children in the study. An increase was also observed in the overall quality of life which was measured across a range of variables, including cognition, general health, behavior, and social activity.
Importantly, the effectiveness of the cannabis oil therapy did appear to be tied to the dosage, as the group who reached the target dose also experienced the greatest reduction in seizure frequency when compared to their condition at the start of the study.
Future recommendations
The authors believe this study is strong evidence that CBD/THC cannabis oil can bring about a significant improvement in the lives of children with Dravet syndrome, with manageable side effects. The study also provides a wealth of information surrounding commonly tolerable dosages, and the varying benefits at different dosage levels, which is important information to have if CBD/THC cannabis oil is to become a common therapeutic for treating drug-resistant epilepsy.
In terms of future research, the authors do note that researching the potential impact of the “entourage effect” between a wider range of cannabinoids and terpenes could lead to the creation of medicinal cannabis oils with fewer side effects.
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