Other beneficial effects include decreased seizures, increased alertness, better mood, and better sleep. Side effects included drowsiness and fatigue. Our survey shows that parents are using cannabis enriched with cannabidiol as a treatment for children with treatment-resistant epilepsy. Due to the increasing number of states that allow access to medicinal cannabis, its use will likely be a growing concern for the epilepsy community. There are no safety and tolerability data for the use of cannabis enriched with cannabidiol among children. Objective measures of a standardized pure cannabidiol preparation are needed to determine whether it is safe, well tolerated, and effective in controlling seizures in this difficult-to-treat pediatric population.

Introduction

Childhood epilepsies beginning in the first years of life are frequently characterized by seizures resistant to available treatments, including antiepileptic drugs (AEDs), a ketogenic diet, high-dose steroids, and surgery. A high seizure load in early childhood probably contributes to the severe cognitive, behavioral, and motor delays common in these children.

When the right treatments don’t control your child’s seizures, some parents turn to alternative treatments. One of these alternative treatments is cannabis enriched with cannabidiol. The cannabis plant contains approximately 80 cannabinoids, of which cannabidiol and Δ9-tetrahydrocannabinol (THC) are the two most abundant.

Cannabidiol and THC have very different physiological effects. Most importantly, cannabidiol is not psychoactive. In recent years, the medical uses of cannabis have focused on cannabidiol, both for its non-psychoactive nature and for its promise in treating the disease. However, in states where medicinal cannabis is legal, cannabidiol is currently only available in whole plant preparations that contain all the components of the cannabis plant, including THC. This poses significant risks in administering cannabidiol-enriched cannabis to epileptic children. Firstly, cannabis use during development has been correlated with adverse effects on brain development and cognition, mainly due to THC. Second, THC can be seizure in epileptic brains.

In contrast to THC, numerous studies conducted over the past 40 years demonstrate the anticonvulsant effects of pure cannabidiol in animal models of partial and generalized seizures, including lighter and acute models. In humans, two small, placebo-controlled studies examined pure cannabidiol in adults with treatment-resistant epilepsy. In 1978, Mechoulam randomly provided nine patients at 200 mg / day of pure cannabidiol or placebo. During the three-month trial, two out of four cannabidiol-treated patients were seizure-free, while seizure frequency was unchanged in the five patients receiving placebo.

In a second small clinical trial, 15 adult patients suffering from treatment-resistant generalized secondary epilepsy were randomized to placebo or 400 mg of pure cannabidiol daily for up to 18 weeks. Among the eight cannabidiol patients, four had a marked reduction and three had a partial reduction in seizures. One of the seven placebo-treated patients experienced a partial reduction in seizures. The most common side effect of pure cannabidiol was drowsiness. No patient reported psychoactive effects. Conversely, an open study showed that cannabidiol was ineffective in controlling seizures; Ames and Cridland reported that seizure frequency was unchanged in 12 institutionalized patients with uncontrolled seizures receiving 200 mg of pure cannabidiol daily.

With the legalization of medical cannabis in a growing number of states, parents of children with uncontrolled attacks have chosen to treat their children’s seizures with cannabis enriched with cannabidiol. This trend has produced an online presence of parents describing cannabis enriched with cannabidiol in children with epilepsy. We asked parents of a Facebook group to anonymously fill out a survey about their experience of giving cannabidiol-enriched cannabis to their children in order to obtain information on the current use of cannabis enriched with cannabidiol as an alternative treatment for childhood epilepsy.

Methods

The institutional review board at Stanford University judged that the study was exempt from requiring a full review by the board of directors. Study data was collected and managed using REDCap’s electronic data capture tools housed at the Stanford Center for Clinical Informatics. REDCap (Research Electronic Data Capture) is a secure web application designed to support data capture for research studies. The survey consisted of 24 questions that measured clinical factors, including the diagnosis and types of seizures, and the reported effect of cannabis-enriched cannabis by parents on seizure frequency and side effects of the child. The survey was presented to a Facebook group of approximately 150 parents who support the use of cannabis enriched with cannabidiol to treat seizures in their children with treatment-resistant epilepsy. The survey link was posted and displayed for two weeks, then republished at the top of the group page for another two weeks. Twenty parents responded to the survey. Nineteen responses met the inclusion criteria – diagnosis of treatment-resistant epilepsy and use of cannabis enriched with cannabidiol – and were included in the analysis. A response was excluded because the child’s diagnosis did not include epilepsy.

Because the results of the Cannabidiol-enriched cannabis survey had a large number of patients with Dravet syndrome and reported positive results for seizure control and side effects, we wanted to assess the parents’ response to the same questions with A well known and effective treatment for Seizures in Dravet syndrome, Stipenthol. This would allow us to see if the parents’ responses to our seizure burden questions were similar to the results of a stiripentol clinical trial. Furthermore, the side effects between the two drugs could be compared. For this purpose, the same survey was administered substituting stiripentol instead of cannabis enriched with cannabidiol. The stiripentol survey was presented to a different Facebook support group made up of parents of children with Dravet Syndrome with approximately 800 members. The stiripentol survey link was also initially released for two weeks and repositioned at the top of the group page for an additional two weeks. Twenty-two parents responded to the stiripentol survey and all responses were included in the analysis. The responses of both surveys were descriptively analyzed.

Methods

The institutional review board at Stanford University judged that the study was exempt from requiring a full review by the board of directors. Study data was collected and managed using REDCap’s electronic data capture tools housed at the Stanford Center for Clinical Informatics. REDCap (Research Electronic Data Capture) is a secure web application designed to support data capture for research studies. The survey consisted of 24 questions that measured clinical factors, including the diagnosis and types of seizures, and the reported effect of cannabis-enriched cannabis by parents on seizure frequency and side effects of the child. The survey was presented to a Facebook group of approximately 150 parents who support the use of cannabis enriched with cannabidiol to treat seizures in their children with treatment-resistant epilepsy. The survey link was posted and displayed for two weeks, then republished at the top of the group page for another two weeks. Twenty parents responded to the survey. Nineteen responses met the inclusion criteria – diagnosis of treatment-resistant epilepsy and use of cannabis enriched with cannabidiol – and were included in the analysis. A response was excluded because the child’s diagnosis did not include epilepsy.

Because the results of the Cannabidiol-enriched cannabis survey had a large number of patients with Dravet syndrome and reported positive results for seizure control and side effects, we wanted to assess the parents’ response to the same questions with A well known and effective treatment for Seizures in Dravet syndrome, Stipenthol. This would allow us to see if the parents’ responses to our seizure burden questions were similar to the results of a stiripentol clinical trial. Furthermore, the side effects between the two drugs could be compared. For this purpose, the same survey was administered substituting stiripentol instead of cannabis enriched with cannabidiol. The stiripentol survey was presented to a different Facebook support group made up of parents of children with Dravet Syndrome with approximately 800 members. The stiripentol survey link was also initially released for two weeks and repositioned at the top of the group page for an additional two weeks. Twenty-two parents responded to the stiripentol survey and all responses were included in the analysis. The responses of both surveys were descriptively analyzed.

Results of the survey on the use of CBD, for patients with epilepsy.

The results of the Cannabidiol-Enriched Cannabis Survey are summarized below. The children were between 2 and 16 years old. Thirteen children had Dravet syndrome (one of whom had epilepsy in women with mental retardation, EMFR), four children had Doose syndrome, and one had Lennox-Gastaut syndrome and idiopathic early-onset epilepsy. Children experienced a variety of seizure types, including focal, tonic-clonic, myoclonic, atonic, and infantile spasms. In all cases except patient 14 (age 2 years), children experienced treatment resistant epilepsy for more than 3 years before trying cannabis enriched with cannabidiol. The 2-year-old boy had experienced intractable seizures for 16 months before trying cannabis enriched with cannabidiol. The children had unsuccessfully tried an average of 12 other antiepileptic drugs before their parents began cannabidiol-enriched cannabis treatment. The doses of cannabidiol that parents reported they provided ranged from less than 0.5 mg / kg / day to 28.6 mg / kg / day. The THC doses contained in these samples were reported to range from 0 to 0.8 mg / kg / day.

To obtain dosage information, parents reported that their preparations were tested in commercial medical cannabis testing facilities. The frequency of seizures before administering cannabis enriched with cannabidiol ranged from 2 per week to 250 per day. The duration of administration of cannabis enriched with cannabidiol ranged from two weeks to more than a year. Sixteen (84%) of the 19 parents reported a reduction in the frequency of their children’s seizures. Two parents reported that their son became seizure free after more than 4 months of using cannabis enriched with cannabidiol. Of the remaining 14 parents who reported a change in seizure frequency, 8 reported a greater than 80% reduction in seizure frequency, three reported a reduction in seizure frequency of more than 50%, and three reported a reduction seizure frequency greater than 25%. Three parents reported no change. Twelve parents refused to give their child another antiepileptic drug after starting treatment with cannabis enriched with cannabidiol.

Summary of survey responses

The beneficial effects of cannabis enriched with cannabidiol, in addition to reduced seizures, included better mood (15/19, 79%), increased alertness (14/19, 74%), better sleep (13/19, 68 %) and decrease in self-stimulation 6/19, 32%). Negative side effects included drowsiness (7/19, 37%) and fatigue (3/19, 16%). Side effects reported while taking other antiepileptic drugs include rash, vomiting, irritability, dizziness, confusion, and aggressive behavior, none of whom were reported to use cannabis enriched with cannabidiol.

Side effects of treatment with enriched CBD.

To understand if our questions could produce results similar to the results of clinical trials, we asked for answers to an identical survey that will replace cannabis enriched with cannabidiol with other antiepileptic drugs in use for Dravet syndrome. Parents of a Facebook group were surveyed about stiripentol, which is approved only in Europe (although Americans can get it). We asked these parents to report how stiripentol affects the frequency of their child’s seizures, as well as what side effects were evident from the drug. Fifteen of the 22 (68%) parents reported that stiripentol reduced their child’s seizure frequency. Four parents reported a substantial increase in seizure frequency, while three parents reported no change. Common negative side effects reported for stiripentol included decreased appetite (5/22, 23%), weight loss (6/22, 27%), insomnia (4/22, 18%), and increased self-stimulation (3 / 22, 14%). The reports in response to our survey are consistent with published data on the effects of stiripentol in children with Dravet syndrome, and I support that our survey questions identify seizure and side effects similar to the results of clinical trials.

Discussion

Summary

We found that parents of children with severe treatment-resistant epilepsy are using cannabis enriched with cannabidiol to treat their child’s epilepsy. Parents report a high success rate in reducing seizure frequency with this treatment. Cannabidiol-enriched cannabis appears to be well tolerated in behavior, with some positive side effects not commonly associated with other antiepileptic drugs. There are, of course, multiple limitations of an anonymous parent survey.

We are unable to verify children’s dose or response to cannabis enriched with cannabidiol. We are reaching out to a group of parents who have a continuing interest in using cannabis enriched with cannabidiol for their child’s seizures that were likely selected for positive results. However, the overall positive results on seizure control in a refractory group of childhood epilepsies suggest that further studies of cannabidiol are warranted.

Parents report reduced seizures

The report on the reduction of the epileptic load in the surveyed population is surprising. The children comprised a population of highly refractory epilepsy, most with Dravet syndrome, a severe form of childhood epilepsy that often does not respond to available treatments, including antiepileptic drugs, the ketogenic diet, and the vagus nerve stimulator.

The children had not responded to an average of 12 antiepileptic drugs before using cannabis enriched with cannabidiol. Children experienced various types of seizures, and reports from parents suggest that cannabis enriched with cannabidiol may be effective for various seizures. The limited size of our survey and the small representation of syndromes other than Dravet do not provide additional guidance on the types of epilepsy to follow in clinical trials. However, it is important to note that the diagnoses and seizure types reported in this anonymous survey could not be validated by an experienced clinician.

Parents report favorable side effect profile

Quality of life surveys show that the adverse effects of antiepileptic drugs have as much impact on the patient’s ability to enjoy life as seizures. Our survey reports that cannabis enriched with cannabidiol is well tolerated in behavior and can have beneficial effects on cognition and mood. Many parents reported that their children experienced better sleep, increased alertness, and better mood while taking cannabis enriched with cannabidiol. These beneficial side effects are rarely reported with pediatric use of other antiepileptic drugs. Additionally, many of the negative side effects commonly associated with AEDs, such as irritability, insomnia, and aggressive behavior, were notably absent from parent reports of cannabis enriched with cannabidiol. Due to the apparent efficacy of cannabis enriched with cannabidiol, 12 parents reported that they weaned their child from other antiepileptic drugs, thereby increasing the child’s quality of life by eliminating the negative side effects associated with those other drugs.

Prejudice problems

We acknowledge that this survey has multiple biases that prevent us from drawing strong conclusions about the overall efficacy of cannabis enriched with cannabidiol in pediatric epilepsy. Positive reports of seizure control and side effects led us to investigate whether the wording of the questions produced strong positive bias.

We conducted an additional survey, using the same questions, of parents using stiripentol, a medication that is approved for the treatment of Dravet syndrome in Europe. Our results from the stiripentol survey are consistent with published studies on the efficacy and tolerability of stiripentol.

Because the responses to the stiripentol survey coincide with published data on the effects of stiripentol, it is unlikely that the formulation of the survey questions was inherently biased. Still, there remains a bias in subject selection, in the sense that parents involved in the Facebook group were advocates of using cannabis enriched with cannabidiol for their children.

Future directions

As parents are increasingly using artisanal cannabis preparations enriched with cannabidiol in an attempt to reduce the child’s seizure load, it is essential to obtain more data on the safety and efficacy of cannabidiol. These poorly regulated preparations may not represent the potential benefits and risks of pure cannabidiol. Formal studies to determine the safety, optimal dosage, tolerability, and efficacy of a standardized cannabidiol preparation in different populations of children and adults with epilepsy will provide the necessary data to determine whether cannabidiol has a place in the treatment of epilepsy. .