“Dravet syndrome (DS) is a debilitating developmental disorder typified by severe seizures and delayed onset of psychomotor deficits.
In addition to increasing the risk for sudden unexpected death in epilepsy (SUDEP), the medically refractory status epilepticus in DS can be life-threatening, which makes it crucial to identify drugs to reduce seizures.
The quest for a viable drug to limit seizures in DS has intersected with the recent excitement over the potential use of cannabinoids as antiepileptic agents, leading to extensive anecdotal reports of the potential for cannabinoids to limit seizures in DS
Cannabinoids are active derivatives of the marijuana plant, Cannabis sativa.
The study reveals a strong preclinical basis for the use of CBD in DS. They find that CBD pre-treatment reduces both duration and severity of thermally-induced behavioral seizures.
In conclusion, Kaplan and colleagues provide the first preclinical demonstration that CBD may help alleviate seizures in a mouse model of DS validating the translational potential of CBD in patients with DS.
The demonstration that CBD improves deficits in social interactions in DS launches an exciting therapeutic possibility of alleviating behavioral impairments that persist beyond the seizures and pave the way for mechanistic studies that could positively impact treatment of autism spectrum disorders.”
“A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy.
In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons.
CONCLUSIONS & IMPLICATIONS:
In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function.”
“Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy.
Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice.
Our results suggest that the CB2 receptor agonists might be clinically useful as an adjunct treatment against seizure spread and status epilepticus and concomitant oxidative stress, neurotoxicity and cognitive impairments.”
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome.
Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated.
CLASSIFICATION OF EVIDENCE:
This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.”
“Epilepsy is one of the most common chronic neurological disorders in dogs characterized by recurrent seizures. The endocannabinoid (EC) system plays a central role in suppressing pathologic neuronal excitability and in controlling the spread of activity in an epileptic network. Endocannabinoids are released on demand and their dysregulation has been described in several pathological conditions. Recurrent seizures may lead to an adverse reorganization of the EC system and impairment of its protective effect. In the current study, we tested the hypothesis that cerebrospinal fluid (CSF) concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2AG) are altered in epileptic dogs. Concentrations of AEA and total AG (sum of 2AG and 1AG) were measured in 40 dogs with idiopathic epilepsy and in 16 unaffected, healthy control dogs using liquid chromatography combined with tandem mass spectrometry.
AEA and total AG were measured at 4.94 (3.18 – 9.17) pM and 1.43 (0.90 – 1.92) nM in epileptic dogs and at 3.19 (2.04 – 4.28) pM and 1.76 (1.08 – 2.69) nM in the control group, respectively (median, 25 – 75% percentiles in brackets). The AEA difference between epileptic and healthy dogs was statistically significant (p < 0.05). Values correlated with seizure severity and duration of seizure activity. Dogs with cluster seizures and/or status epilepticus and with seizure activity for more than six months displayed the highest EC concentrations.
In conclusion, we present the first endocannabinoid measurements in canine CSF and confirm the hypothesis that the EC system is altered in canine idiopathic epilepsy.”
“In conclusion, we demonstrated an elevation of CSF AEA concentrations in dogs with idiopathic epilepsy. The highest AEA concentrations were found in dogs with severe seizures and a long disease history. Possibly, the activation of the EC system serves as a counter-mechanism in order to regulate the seizure-threshold in epilepsy. However, the EC system can either alter or be altered by seizure activity, so that further, prospective studies are warranted to investigate pathological mechanisms. Despite endocannabinoids can be synthesized “on demand”, the EC system should be considered for development of new treatment strategies against epilepsy.”
“Refractory epilepsies in children present a major burden for patients and their families. Cannabidiol (CBD) has been suggested as a potential treatment for refractory epilepsies. The aim of this study was to evaluate the effectiveness of add-on therapy with CBD for the treatment of refractory childhood epilepsies.
Patients with childhood-onset refractory epilepsy, treated at the tertiary epilepsy center of the University Children’s Hospital Ljubljana, Slovenia, were included in the study. Add-on therapy with CBD was initiated once the child’s epilepsy was categorized as pharmacoresistant to other antiepileptic drugs/therapies. The dosage of CBD was gradually increased to at least 8mg/kg/day. The effect of CBD treatment was evaluated by the reduction in seizure burden and presence of side effects (positive and negative). Serial electroencephalography was performed in some children.
Sixty-six patients were included in the analysis. Thirty-two (48.5%) patients had a more than 50% improvement regarding seizure burden, 14 of whom (21.2%) became seizure-free. None of the patients reported worsening of seizure frequency, but CBD had no effect in 15 (22.7%) patients. Some patients reported less vigorous seizures, shorter duration of seizures, shorter time to recovery, and other positive side effects of CBD treatment. Adverse effects were reported in 5/66 children.
In our cohort of patients, CBD was found to have potential benefits as add-on therapy for refractory childhood epilepsies, mainly by reducing seizure burden.”