cannabidiol cbd epilepsy

A prescription cannabidiol product offers a new therapeutic option for patients with Lennox-Gastaut syndrome and Dravet syndrome.

TABLE 1

The initial dose of CBD-Rx is 2.5 mg/kg twice daily for 1 week, then increasing to 5 mg/kg twice daily. Further increases can be made as needed and tolerated to a maximum of 10 mg/kg twice daily.3 Dose adjustments are necessary for moderate or severe hepatic disease.3 For the patient case, the recommended dose is 40 mg twice daily, increasing to 80 mg twice daily after 1 week. The dosage form is a 100-mg/mL strawberry-flavored oral solution and is administered as 0.4 mL for the first week, then 0.8 mL afterward. Patients should be given a calibrated dosing device to assure accurate measurement. A 5-mL calibrated oral syringe is provided with product packaging, but often, patients need a 1-mL device.3 There are significant differences in pharmacokinetic parameters when the dose is given with food. Eight subjects with intractable epilepsy were compared after eating a high-fat meal and after fasting ( Table 3 ).30 Record-keeping of seizures during this study was poor, but 1 patient noted a decrease from an average of 7 seizures daily in a fasting state to 1 seizure/d in a fed state. No differences in cognition were noted between the fasting and fed conditions.30 Thus, patient’s caregivers should try to achieve consistency with dosing regarding meals. Because of the potential of CBD-Rx to cause nausea and vomiting, dosing with food may be preferred.

TABLE 3

The studies of CBD-Rx in LGS demonstrate significant improvement in number of seizures, particularly drop attacks, in patients. However, they are unlikely to become seizure-free. Based on the results of these studies, the patient is a good candidate for CBD-Rx therapy. The patient’s epilepsy is treatment resistant despite treatment with agents that have efficacy data in LGS. The patient experiences several drop seizures weekly, increasing the risk of injury. The patient has had therapeutic trials of many agents with limited efficacy, and CBD-Rx presents a new option with good clinical trial–based evidence to support its use. The CBD-Rx can be added directly to the regimen with alterations in other medications if adverse effects, such as sedation, are bothersome. If the CBD-Rx proves effective, the patient’s medication regimen could then be streamlined by tapering 1 or more of the other medications.

Cannabidiol cbd epilepsy

The available results also highlight the efficacy of CBD as adjunctive to common AEDs. The mechanism by which CBD interacts with other AEDs is not yet fully known, as many metabolic pathways involved in this interaction are still unknown. In addition, not all the molecular targets used by the CBD to exercise its antiepileptic action are yet known. However, the results obtained to date encourage the use of CBD associated with AEDs.

The phase 3 clinical trial <"type":"clinical-trial","attrs":<"text":"NCT02224560","term_id":"NCT02224560">> NCT02224560 (GWPCARE3) included 225 patients with LGS (2 to 55 years) with two or more seizures/week. This study was to evaluate the safety and efficacy of the CBD oral solution (GWP42003-P) as an adjunctive treatment of other antiepileptic drugs. The patients were divided into 3 groups and treated with CBD at the dose of 10 mg/kg/day or 20 mg/kg/day or with placebo for 14 weeks. During the treatment, SAEs such as pneumonia, status epilepticus, elevated aspartate aminotransferase concentration, elevated alanine aminotransferase concentration and elevated γ-glutamyltransferase concentration, occurred in 19.40% of patients treated with 10 mg/kg/day of CBD, in 15.85% treated with 20 mg/kg/day and in 10.53% of the placebo group. Increases in serum aminotransferase concentrations occurred only in patients treated with placebo. While, non-serious AEs (diarrhea, vomiting, decreased appetite, pyrexia, fatigue, somnolence, upper respiratory tract infection, nasopharyngitis) have been observed in 53.73% of 10 mg/kg daily group, in 76.83% of 20 mg/kg/day group, and in 52.63% of the placebo group. A median percent reduction from baseline in drop-seizure frequency was 37.2% in the 10 mg/kg/day CBD group, 41.9% in the 20 mg/kg/day CBD group, and 17.2% in the placebo group. The results reported by the authors show that the addition of the CBD to conventional antiepileptic therapy reduces the frequency of seizures in a dose-dependent manner [75].

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.

Data obtained from trials authorized by local ethics committees (https://www.ncbi.nlm.nih.gov/pubmed/). The table shows the efficacy and safety of CBD in different forms of epilepsy. In all studies, CBD is used as adjunctive therapy to conventional antiepileptic drugs.

6. Conclusions

CBD: Cannabidiol; TEAEs: Treatment-emergent adverse events; SAEs: serious adverse events; AST: aspartate transferase; ALT: alanine transferase.

Eighteen participants who completed trial <"type":"clinical-trial","attrs":<"text":"NCT02565108","term_id":"NCT02565108">> NCT02565108 were transferred to the open-label extension (OLE) trial <"type":"clinical-trial","attrs":<"text":"NCT02564952","term_id":"NCT02564952">> NCT02564952. The OLE phase was a safety study. Initially, all participants received CBD at a dose of 20 mg/kg/day, thereafter the dose was decreased or increased to a maximum of 30 mg/kg/day. All individuals during the study continued to receive CLB. In addition to CLB, participants could not take more than two other AEDs during the study. Only seven of the 18 participants completed the study, 11.11% showed SAEs (status epilepticus, seizure, alanine aminotransferase abnormal, aspartate aminotransferase abnormal γ-glutamyltransferase abnormal). While, 94.44% of patients presented no-serious AEs such as diarrhoea, vomiting, headache, hyponatraemia, dizziness, seizure, somnolence, irritability, respiratory tract infection. The high rate of AEs in the concomitant use of the CBD and CLB for prolonged periods of time may be unsafe.

The <"type":"clinical-trial","attrs":<"text":"NCT02660255","term_id":"NCT02660255">> NCT02660255 is an observational, open-label, flexible dose study. The aim of this trial is to evaluate the safety and efficacy of Epidiolex, in addition to common AEDs. The study will be recruited subjects aged 1-60 years with treatment-resistant epilepsy. Patients prior to enrolment will be treated with 1–4 AEDs on stable settings from least 1 month. Epidiolex will be administered for 1 year and 9 months. To date, no superior information and results are available, yet.

5. Cannabidiol: Clinical Trials for Epilepsy

The most well-known epilepsies are DS, Sturge-Weber Syndrome (SWS), Tuberous Sclerosis Complex (TSC) and West Syndrome (WS) and LGS. DS is a rare encephalopathy, which has its onset in the first year of life [41]. DS is associated with the mutation in the gene encoding the α1 subunit of the voltage gated sodium channel (SCN1A) [42]. SWS is caused by a somatic mutation of the GNAQ gene (9q21) that encodes the Gq protein, involved in the intracellular signal of several G protein-coupled receptors that control the function of various growth factors and vasoactive peptides [43]. Patients manifest neurological abnormalities of variousdegrees, focal epileptic seizures [44]. TSC is an autosomal dominant disease, caused by a mutation of two genes: TSC1 (localized on chromosome 9p34.3) that encodes for hamartin and TSC2 (localized on chromosome 16p13.3) that encodes for tubulin. Often TSC patients present generalized epilepsy. WS or Infantile Spasm (IS) is the epileptic encephalopathy. This syndrome is characterized by genetic heterogeneity and the mutated gene most frequently observed in patients with this syndrome is CDKL5 (cyclin-dependent kinase-like 5) [45]. WS is characterized by the association between axial spasm discharges and psychomotor retardation [46]. LGS is a severe epileptic encephalopathy of childhood. This syndrome is a rare condition likely associated with a genes mutation. Nevertheless, to date, it is quite unclear how the involved genes may cause this syndrome mainly characterized by recurrent seizures from early in life. An epileptic form that does not respond to therapy with at least two or three appropriately selected anti-epileptic drugs (AEDs) is defined as TRE and this is estimated to affect 30% of patients [47,48].

Epilepsy is a chronic neurological disorder. About 30% of epilepsy patients are affected by Treatment-Resistant Epilepsy (TRE) due to the failure of common anti-epileptic therapies [34]. This form of epilepsy is characterized by recurrent seizures that negatively affect the quality of life.