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cbd anticonvulsant

Cbd anticonvulsant

Subsequently, GW launched a second Phase 3 trial, GWCARE2 ( <"type":"clinical-trial","attrs":<"text":"NCT02224703","term_id":"NCT02224703">> NCT02224703), to evaluate DS patients’ responses to either a low (10 mg/kg/day) or a high dose (20 mg/kg/day) of GWP42003-P for 14 weeks. The study, still recruiting, plans to enroll 150 participants, both children and adults (2 to 18 years). The results are not available.

In the clinical trial <"type":"clinical-trial","attrs":<"text":"NCT03676049","term_id":"NCT03676049">> NCT03676049, CBD will be administered as an adjunct to all current AEDs in 5–10 patients (aged between 5 and 19) with refractory epilepsy. The CBD oral solution used for treatment, with prior approval from the National Institute on Drug Abuse was prepared at the University of Mississippi, and subsequently received FDA approval for compassionate use. A dosing titration period will start with 100 mg/day, and will be titrated monthly as tolerated based on clinical response, up to 300 mg/day. During the treatment period the patients will be subjected to control visits at the baseline, at the fourth, at the eighth and at the twelfth weeks. During these visits the efficacy of the treatment will be evaluated, observing the laboratory tests, quality of life of the patient, the profile of the side effects and the crisis count. Patients who after 3 months of treatment show stability could continue the use of CBD for another 3 months.

5. Cannabidiol: Clinical Trials for Epilepsy

Szaflarski, et al. [89] conducted an open-label, Expanded-Access Program (EAP) in 25 epilepsy centers in the USA, and it was approved by an institutional review board at each site. The aim of this study was to evaluate the safety and efficacy of CBD oral solution (Epidiolex), in addition to common AEDs in patients with different forms of treatment-resistant epilepsies (TREs). For the study, 607 patients with a mean age of 13 were enrolled. All patients were included in the safety study, while 508 were included in the efficacy study. Treatment involved a 4-week baseline period followed by a 96-week treatment period. During treatment, patients received Epidiolex at the initial dose of 2–10 mg/Kg up to a maximum dose of 25-50 mg/Kg daily. 146 patients (mostly due to lack efficacy [15%] or AEs [5%]) from the safety study group and 136 patients (mostly due to lack efficacy [15%] or AEs [4%]) from the efficacy group were withdrawn from the study. SAEs were found in 33% of patients such as convulsion (9%), status epilepticus (7%), pneumonia (5%), and vomiting (3%). Instead, AEs manifested in 88% of patients the most common were diarrhea (29%), somnolence (22%), and convulsion (17%). Already after 12 weeks of treatment, the median monthly frequency of seizure convulsions was reduced by 51% and by 48 % the frequency of total seizures. These reductions remained stable during the 96 weeks of treatment. Between weeks 12 and 96 the average dose of CBD was 25 mg/kg daily, 55% of patients at follow-up had reduced the dose. Half of the patients taking concomitant CLB and valproate reduced the dose compared to baseline during the study. While, most of those who take simultaneously levetiracetam, had remained at their basal doses. The data obtained from this study show that CBD as an adjunct treatment to common AEDs can be used in the long-term effective treatment in patients with TRE.

To date, available safety data show that the administration of CBD associated with other AEDs causes non-serious adverse events, which can be resolved reducing the dose of CBD and/or common AEDs. In this context, particular attention should be paid when CBD is associated with valproate and CLB. Specifically, abnormal liver function was noted in participants taking concomitant valproate, therefore, it is necessary to monitor serum levels of these compounds and their respective metabolites. Instead, when CBD is associated with CLB it induces an increase in its metabolites. Since the adverse effects are not serious, this association can be considered safe.

Table 2

Another study conducted by Sands, et al. [84] assessed the long-term safety, tolerability and efficacy of CBD to children with refractory epilepsy. This study was approved by the Human Research Ethics Committee of the UCSF Benioff Children’s Hospital. The CBD oral solution (Epidiolex) was administered in addition to other anti-epileptic treatments in 26 patients (aged 1 to 17 years). The doses of concomitant antiepileptic drugs had to be stable during the 4-week of baseline period and had to remain stable during the first three months of treatment. CBD was administered at the starting dose of 5 mg/kg daily and subsequently, weekly dosage was measured in increments of 5 mg/kg daily up to a maximum dose of 25 mg/kg daily. The duration of therapy ranged from 4 to 53 months. The patients underwent blood tests performed during the baseline period, after 1, 2 and 3 months and thereafter every 3 months from treatment. Furthermore, the minimum concentrations of antiepileptic drugs were evaluated. The frequency of seizures and AEs was monitored during the treatment period. The primary outcome of the study was to test the efficacy of CBD in terms of > 50% reduction in the frequency of motor seizures. Fifteen of 26 patients discontinued treatment, one due to a status epilepticus, one for severe weight loss, all others for lack of efficacy. Instead, six patients showed SAEs as status epilepticus (n = 3), catatonia (n = 2) and hypoalbuminemia (n = 1). 21 out of 26 patients reported no serious AEs among which the most frequent were: reduced appetite (n = 10), diarrhoea (n = 9), and weight loss (n = 8). In patients showing significant weight loss, the doses of CBD were reduced. Changes in the concentrations of antiepileptic drugs were observed in four patients. Three of them reported increased CLB concentrations, one reported an increment in phenobarbital contractions. In three patients was observed an increment in aspartate aminotransferase and alanine transferase levels when CBD was co-administered with valproate. The reduction in the frequency of seizures > 50%, was rediscovered in 38.4% of patients after 3 months of treatment, in 56.7% after 6 months, in 42.3% after 9 months, in 38.4% after 12 months, 42.3% after 18 months and 34.6% after 24 months. In conclusion, after 24 months of treatment, of the 26 patients enrolled, only nine continued CBD as adjunctive therapy. Of these patients, seven had a 50% reduction in the frequency of motor crises, three of which remained completely free of seizures. Only seven of the nine patients who continued treatment showed a reduction in seizure frequency > 50% after 36 months. The results reported by the authors showed that long-term CBD results in a clinically significant reduction in seizure frequency, and a low percentage of SAEs. Moreover, because treatment was stopped after a few months in most patients, the number of patients exposed to CBD for a long time is low and the rate of adverse effects over time may be underestimated.

“This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies. And, the FDA is committed to this kind of careful scientific research and drug development,” said FDA Commissioner Scott Gottlieb, M.D. “Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes. We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products. But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”

The FDA prepares and transmits, through the U.S. Department of Health and Human Services, a medical and scientific analysis of substances subject to scheduling, like CBD, and provides recommendations to the Drug Enforcement Administration (DEA) regarding controls under the CSA. DEA is required to make a scheduling determination.

Lennox-Gastaut syndrome begins in childhood. It is characterized by multiple types of seizures. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5. More than three-quarters of affected individuals have tonic seizures, which cause the muscles to contract uncontrollably. Almost all children with Lennox-Gastaut syndrome develop learning problems and intellectual disability. Many also have delayed development of motor skills such as sitting and crawling. Most people with Lennox-Gastaut syndrome require help with usual activities of daily living.

CBD is a chemical component of the Cannabis sativa plant, more commonly known as marijuana. However, CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC).