"Use of CBD in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials"

CBD has received a great scientific interest thanks to its medical applications. 

In recent years, the scientific community has shown interest in this compound also due to its good safety profile and neuroprotective properties  in several neurodegenerative diseases.

CBD also generating interest due to its therapeutic properties such as antidepressant, antipsychotic, analgesic, and antitumor. 


In addition, it has been shown that CBD can significantly reduce two important forms of anxiety, namely obsessive-compulsive disorder and post-traumatic stress disorder.

CBD shows anti-inflammatory properties in several experimental studies, modulating some pro-inflammatory cytokines and tumor necrosis factor as well as regulation of cell cycle and immune cells’ functions

Moreover, for a long time, the CBD has been investigated for its anticonvulsant effects. Several studies confirmed its efficacy in the treatment of epileptic seizures, especially in pediatric age. In 2016, the first results of  clinical trials showed beneficial effects of CBD in treatment-resistant seizure disorders, including Lennox-Gastaut Syndrome (LGS) and Dravet syndromes (DS).

The purpose of this paper wich published in  12 April 2019 from the 'Molecules Open Access Journals' 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.

-CBD and Molecular Targets in Epilepsy

TRPV1 is a non-selective channel that shows a high Ca2+ 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 Ca2+, with consequent neuronal excitability

However, it has been observed that the CBD action towards TPRV1 determines one a desensitization of these channels with normalization of intracellular Ca2+ (The calcium ion Ca2+ has a critical role in the rapid responses of neurons and muscle cells)

CBD also shows action towards the receptor GPR55, a class of receptors involved in the modulation of the synaptic transmission. The action of CBD towards these receptors would seem to attenuate synaptic transmission with consequent antiepileptic effects.

Also an important enzyme target of CBD involved in epilepsy is cytochrome CYP450. CBD inhibits CYP450, but this mechanism does not seem to be directly involved in the antiepileptic mechanism. But it seems to be responsible for the hepatic metabolism of a variety of AEDs (Anti-Epileptic Drugs), as shown by the combined administration of CBD and clobazam (CLB).

-CBD in Clinical Trials for Epilepsy

All clinical studies assess the safety and/or efficacy of CBD in addition to common AEDs. Most of these studies enrolled pediatric patients with diagnoses of genetically based epilepsy, LGS, DS and resistant to common antiepileptic treatments.

-A clinical trial has evaluated efficacy and safety of the CBD oral solution at three different doses administered for 10 consecutive days in 61 children (1–17 years) with drug-resistant forms of epilepsy. 

An improvement observed in daily seizure activity also the results of this study showed that CBD can be considered safe and tolerable even at high concentrations

-Another multi-center clinical trial was evaluated the efficacy of CBD as complete resolution of spasms and the efficacy and the long-term safety up to 64 weeks of treatment. 

14.3% of children showed complete resolution of spasms and hypsarrhythmia on day 14. In high doses only the 33% showed adverse effects, while no serius adverse effects were recorded. These results confirm the efficacy and safety of the CBD oral solution after 14 days of treatment.

The researchers also notice that "no serius adverse effects occurred in 88.89% of infants, in 92.31% of children and 88.24% of teenagers but  serius adverse effects such as seizures, status epilepticus and mental status changes occurred in 77.78% of infants, in 38.46% of children and 0% of teenagers in hight doses (40 ml/gr/day). These results show that while the administration of CBD cannot be considered safe in infants, but it was generally well tolerated in adults."

Also, in  subsection 'Clinical Trials Approved by Local Ethics Committees' of this review published clinical studies  have been described.

The results of these studies show that "The administration of CBD as an addition to the common AEDs for long periods of time leads to clinically significant reductions in the frequency of convulsive and total seizures in different etiologies of epilepsy. Furthermore, an improvement in the quality of life of these patients was also observed."

-Conclusion

The CBD is a compound extensively studied for its potential efficacy for the treatment of epilepsy. In this review, we reported the studies conducted in infants, children and teenagers affected by epilepsy resistant to common AEDs.

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. 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.

Source: https://www.mdpi.com