“The effectiveness of marijuana in the treatment of epilepsy was originally reported as early as 1800 BC. There is now concrete evidence to suggest the efficacy of cannabis in the treatment of epilepsy, particularly in the refractory group. To summarize, in view of the good outcome in a significant number of patients, which is not significantly worse than other accepted options for patients with refractory epilepsy, it seems that medical cannabis should be considered a viable treatment option.” https://www.ima.org.il/FilesUpload/IMAJ/0/228/114213.pdf https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4041 https://www.ncbi.nlm.nih.gov/pubmed/28457054]]>
Category Archives: Dravet Syndome
Report from a Survey of Parents Regarding the Use of Cannabidiol (Medicinal cannabis) in Mexican Children with Refractory Epilepsy.
“Structured online surveys were used to explore the experiences of the parents of children with refractory epilepsy using medicinal cannabis in Mexico during September 2016. The surveys, which were completed in full, were reviewed, and 53 cases of children aged between 9 months and 18 years were identified. Of these, 43 cases (82%) were from Mexico and 10 (18%) were from Latin American countries. Of the 43 Mexican cases, the diagnoses were as follows: 20 cases (47%) had Lennox-Gastaut syndrome (LGS); 13 cases (30%) had unspecified refractory epilepsy (URE); 8 cases (19%) had West syndrome (WS); 1 case (2%) had Doose syndrome (DS); and 1 case (2%) had Ohtahara syndrome (OS). In total, 47.1% of cases had previously been treated with 9 or more anticonvulsant therapies.
The parents reported a decrease in convulsions when cannabidiol was used in 81.3% of the cases; a moderate to significant decrease occurred in 51% of cases, and 16% of cases were free from seizure. The number of antiepileptic drugs being used was reduced in 9/43 (20.9%) cases. No serious adverse effects were reported, with only some mild adverse effects, such as increased appetite or changes in sleep patterns, reported in 42% of cases.”
https://www.ncbi.nlm.nih.gov/pubmed/28392943
Social correlates of health status, quality of life, and mood states in patients treated with cannabidiol for epilepsy.
“Social characteristics, such as socioeconomic status and race/ethnicity, play a role in the treatment and outcomes of patients with epilepsy (PWE), but little is known about how these factors affect patients receiving cannabidiol (CBD) to treat seizures. This exploratory study examined the sociodemographic profile of patients treated with CBD (n=80) and associations between social factors and patient-centered outcomes – overall health status, Quality of Life in Epilepsy-89 (QOLIE-89), and Profile of Mood States (POMS) – in this population. Associations were examined using Pearson correlations and multiple ordinary-least-squares regression (alpha=0.1). The sample was predominantly white (96%) and non-Hispanic/Latino (96%); 76% of patients had family incomes of $40,000+/year. Some patients/families reported experiencing food scarcity (13%), not being able to make ends meet (6%), or not being able to afford antiepileptic medications (8%). The patients’ health ratings declined with age and income (p≤0.014), and there was a statistically significant interaction (p<0.055) between these variables: for example, a higher-income 10-year-old had a predicted health rating of 3 (“very good”), followed by a higher-income 40-year-old with a rating of 2 (“good”), a low-income 10-year-old with a rating of 1 (“fair”), and a low-income 40-year-old with a rating of 0 (“poor”). This is the first study reporting the social profile of patients taking pharmaceutical grade CBD for the treatment of epilepsy. The results suggest that despite free access to this treatment some patients may not be accessing CBD because of their socioeconomic situation or race/ethnicity. Larger, diverse samples and longitudinal data are needed to more accurately model social factors and patient-centered outcomes in PWE receiving CBD.” https://www.ncbi.nlm.nih.gov/pubmed/28236578]]>
Cannabinoids and epilepsy — Introduction.
“Over the past five years, the lay press and families of children with catastrophic epilepsies popularized the use of cannabis and cannabinoids to treat seizures. Many state legislatures have responded to the pressure from lay groups and have legalized medical cannabis, which is now available to a majority of people in the United States. Patients throughout the world are also obtaining and using cannabinoids to treat their epilepsy. There is an enormous dissociation between the widespread use of cannabis-based therapies to treat diverse epilepsies and our understanding about the efficacy and safety of different cannabinoids in treating different epilepsy syndromes.” http://www.epilepsybehavior.com/article/S1525-5050(17)30042-2/abstract http://www.thctotalhealthcare.com/category/epilepsy-2/]]>
Cannabinoids in treatment-resistant epilepsy: A review.
“Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative. Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD and diverse medical marijuana (MMJ) preparations containing: tetrahydrocannabinol (THC), CBD, and many other cannabinoids in differing combinations. These RCTs have studied the safety and explored the potential efficacy of CBD use in children with Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). The role of the placebo response is of paramount importance in studying medical cannabis products given the intense social and traditional media attention, as well as the strong beliefs held by many parents and patients that a natural product is safer and more effective than FDA-approved pharmaceutical agents. We lack valid data on the safety, efficacy, and dosing of artisanal preparations available from dispensaries in the 25 states and District of Columbia with MMJ programs and online sources of CBD and other cannabinoids. On the other hand, open-label studies with 100mg/ml CBD (Epidiolex®, GW Pharmaceuticals) have provided additional evidence of its efficacy along with an adequate safety profile (including certain drug interactions) in children and young adults with a spectrum of TREs. Further, Phase 3 RCTs with Epidiolex support efficacy and adequate safety profiles for children with DS and LGS at doses of 10- and 20-mg/kg/day. This article is part of a Special Issue titled “Cannabinoids and Epilepsy”.” https://www.ncbi.nlm.nih.gov/pubmed/28188044]]>
A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.
“Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns.” https://www.ncbi.nlm.nih.gov/pubmed/28102593]]>
Pharmacology of cannabinoids in the treatment of epilepsy.
“The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA). It has long been known that ∆9-THC has partial agonist activity at the endocannabinoid receptors CB1 and CB2, though it also binds to other targets which may modulate neuronal excitability and neuroinflammation. The actions of Δ9-THCV and Δ9-THCA are less well understood. In contrast to ∆9-THC, CBD has low affinity for CB1 and CB2 receptors and other targets have been investigated to explain its anticonvulsant properties including TRPV1, voltage gated potassium and sodium channels, and GPR55, among others. We describe the absorption, distribution, metabolism, and excretion of each of the above mentioned compounds. Cannabinoids as a whole are very lipophilic, resulting in decreased bioavailability, which presents challenges in optimal drug delivery. Finally, we discuss the limited drug-drug interaction data available on THC and CBD. As cannabinoids and cannabis-based products are studied for efficacy as anticonvulsants, more investigation is needed regarding the specific targets of action, optimal drug delivery, and potential drug-drug interactions.” https://www.ncbi.nlm.nih.gov/pubmed/28087250]]>
Cannabis and epilepsy: An ancient treatment returns to the fore.
“Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to “hand of ghost” are considered credible, this relationship may span four millennia.
A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with “Indian hemp.”
Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings.
Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids.”
Cannabidiol Reduces Seizures in Various Epilepsy Disorders
“A purified oral formulation of cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) significantly reduces seizures in treatment-resistant epilepsy, according to new research that included double-blind randomized controlled trials of patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), two of the most difficult-to-manage seizure conditions.
The new research, released here at the American Epilepsy Society (AES) 2016 Annual Meeting, also highlights the relative safety of this new drug, a prescription medicine derived from the cannabis plant.”
Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.
“Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy.
We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time.
The children presented typical signs of intoxication by Δ9-THC (inappropriate laughter, ataxia, reduced attention, and eye redness) after using a CBD-enriched extract.
The extract was replaced by the same dose of purified CBD with no Δ9-THC in both cases, which led to improvement in intoxication signs and seizure remission.
These cases support pre-clinical and preliminary clinical evidence suggesting that CBD may be effective for some patients with epilepsy.
Moreover, the cases highlight the need for randomized clinical trials using high-quality and reliable substances to ascertain the safety and efficacy of cannabinoids as medicines.”