Compared with the control group, artisanal CBD users reported lower epilepsy medication-related adverse effects (13% lower) and had greater psychological health satisfaction (21% greater) at the beginning of the study. They also reported lower anxiety (19% lower) and depression (17% lower).
Importantly, 27 patients in the control group at the start of the study started using artisanal CBD products later in the study. After starting CBD, these patients reported significant improvements in physical and psychological health, as well as reductions in anxiety and depression.
Epilepsy, one of the most common nervous system disorders affecting people of all ages, is a neurological condition characterized by recurrent seizures. Treatment for epilepsy includes anti-seizure medications and diet therapy, such as forms of the ketogenic diet. Surgery may be an alternative treatment, especially when medications or diet fail to control seizures, or if drug side effects — including dizziness, nausea, headache, fatigue, vertigo and blurred vision — are too difficult for a patient to tolerate.
Participants completed a web-based survey that included questions regarding quality of life, anxiety and depression, and sleep. They were prompted via email to complete follow-up surveys at three-month intervals for 14 months.
Vandrey says further research is needed to understand how these findings can best be applied to helping people with epilepsy. In the interim, he says, patients should consult with their physician before trying CBD products.
Artisanal (non-pharmaceutical) cannabidiol (CBD) products have become popular in recent years for their apparent therapeutic effects. CBD — a naturally occurring compound of the cannabis plant legally derived from hemp — is used widely as a naturopathic remedy for a number of health conditions, including epilepsy and seizure disorders. Now, Johns Hopkins Medicine researchers, in collaboration with the Realm of Caring Foundation and other institutions, have conducted an observational study with participant-reported data to better understand the impact these products may have on people with epilepsy.
They found that CBD may reduce the adverse effects associated with anti-seizure medications, and seems to improve other aspects of health and quality of life for patients.
A clinical trial of phase II <"type":"clinical-trial","attrs":<"text":"NCT02987114","term_id":"NCT02987114">> NCT02987114, is an open-label, single-center trial, that recruited 16 children (aged 2-15 years), with intractable epilepsy. The aim of this trial was to evaluate the safety, tolerability and efficacy of oral administration of PTL101 (formulation of seamless gelatin matrix green beads containing CBD) as adjunctive therapy for pediatric intractable epilepsy. Patients at least 4 weeks before enrolment had to have stabilized the doses of antiepileptic drugs. This clinical trial has included 4 weeks of observation of clinical parameters and 13 weeks of CBD treatment at an initial dose of 25 mg/kg daily up to the maximum dose of 450 mg/kg. Subsequently the patients were monitored for 2 weeks. The results of this study, not yet available.
CBD: Cannabidiol; TEAEs: Treatment-emergent adverse events; SAEs: serious adverse events; AST: aspartate transferase; ALT: alanine transferase.
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.
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.
The phase 3 clinical trial <"type":"clinical-trial","attrs":<"text":"NCT02224690","term_id":"NCT02224690">> NCT02224690 (GWPCARE4) included 171 patients (aged between 2 and 55 years) with a diagnosis of LGS. Participants had to have taken one or more antiepileptic drugs (the most used was lamotrigine, valproate and CLB) at a stable dose for at least 4 weeks prior to screening as well as interventions for epilepsy. The first endpoint was to aim the efficacy of the CBD oral solution (GWP42003-P) as adjunctive treatment in reducing the number of drop seizures when compared to the placebo. The secondary endpoint was to assess the safety of CBD by measuring AEs using standard severity measures. Individuals were divided into two groups: 85 received placebo and 86 received a CBD at a dose of 20 mg/kg/day for 14 weeks. SAEs (pneumonia, viral infection, alanine aminotransferase increased, aspartate aminotransferase increased, γ-glutamyltransferase increased) occurred in the 23.26% of CBD group and in 4.71% of patients in the placebo group. Serious TEAEs (increased levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase) occurred in four patients in the CBD group. Instead, the most common no serious-AEs (vomiting, diarrhoea, loss of appetite and drowsiness) occurred in the 61.63% of CBD group and in 50.59% of patients in the placebo group. After 14 weeks of treatment, the monthly frequency of seizures decreased by a median of 43·9% from baseline in the CBD group. A reduction in seizures frequency of 50% or more, was reported in 44% of patients in the CBD group and in 24% of patients in the placebo group. The study found that in many patients treated with antiepileptic drugs that included CLB, a higher onset of somnolence was observed. High levels of transaminases were recorded in patients treated with valproate. Nevertheless, the high rate of AEs, the results showed that the administration of long-term CBD oral solution in patients with LGS determines the reduction in seizure frequency compared to placebo .
3. Common Antiepileptic Drugs
Specifically, TRPV1 is a non-selective channel that shows a high Ca 2+ permeability and is involved in the modulation of seizures and in epilepsy. In fact, when active, it promotes the release of glutamate and the increase in Ca 2+ , with consequent neuronal excitability . The antiepileptic action of CBD does not seem to be due to direct interaction with these molecular targets. However, it has been observed that the CBD agonist action towards TPRV1 determines one a desensitization of these channels with consequent normalization of intracellular Ca 2+ . T-Type Ca 2+ , are another class of ion channels with which CBD interacts. These channels control Ca 2+ peaks in neurons and they are involved in the regulation of cell excitability. The activation of these channels due to a hyperpolarization of the membranes of neurons determines an increase in the concentration of intracellular Ca 2+ , in this way the T-Type Ca 2+ channels increase the excitability of neurons. This mechanism is often observed in pathophysiological conditions such as epilepsy . The interaction of the CBD with the T-type Ca 2+ channels causes a blockage of these channels, this mechanism could be responsible for the antiepileptic action, even if there are no studies available that confirm this. Receptors represent other molecular targets that have been evaluated to describe their potential role in epilepsy through interaction with CBD. Serotonin receptor (5-hydroxytryptamine [5-HT]) belonging to the superfamily of the G protein-coupled receptors are divided into seven distinct classes (5-HT1 to 5-HT7). These receptors may depolarize or hyperpolarize neurons, modifying the conductance and/or concentration ionic within the cells. This suggests that 5-HT receptors are involved in epilepsy even though their role is still not entirely clear . CBD shows a high affinity towards two subtypes of serotonin receptors: 5-HT1A e 5-HT2A. These receptors can have different functions and regulatory characteristics, in fact, for example, the activation of 5HT1 receptors in the hippocampus causes an increase of neurotransmission; in contrast, in raphe nuclei, activation of 5-HT1A receptors produces the inhibition of serotonergic neurons . The dysregulation of brain neurotransmission mediated by 5-HT2 might results responsible for the pathophysiology of depression and epilepsy . However, although the role of serotonin receptors in epilepsy is unclear, 5-HT1A e 5-HT2A subtypes may represent a valid therapeutic target through which CBD can perform its anti-epileptic action [61,67]. Opioid receptors (OR) are G-protein-coupled receptors involved in a variety of brain disorders, including epilepsy [68,69]. The CBD at high micromolar concentrations determines the blocking of µ and δ OR, and this block would seem to generate anticonvulsant actions, even if there are still no studies to support this theory. The CBD also shows a good affinity towards the orphan G-protein-coupled receptor (GPR55), a class of receptors involved in the modulation of the synaptic transmission. The agonist action of CBD towards these receptors would seem to attenuate synaptic transmission with consequent antiepileptic effects .
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.