ABSTRACT
The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy.
Subject(s)
Cannabidiol/pharmacology , Cannabinoid Receptor Modulators/pharmacology , Drug Resistant Epilepsy/drug therapy , Epilepsies, Myoclonic/drug therapy , Lennox Gastaut Syndrome/drug therapy , Practice Guidelines as Topic , Cannabidiol/administration & dosage , Cannabidiol/standards , Cannabinoid Receptor Modulators/administration & dosage , Cannabinoid Receptor Modulators/standards , HumansABSTRACT
A cell-free system for studying Sendai virus RNA synthesis was reconstituted from N protein:RNA templates and transfected cell extracts in which the viral N, P and L proteins were expressed. Both transcription (mRNA synthesis) and replication (genome and antigenome synthesis) took place concurrently in these reactions. Viral RNA polymerases engaged in replication (replicases) were found to elongate their chains at a constant speed along the genome (1.7 nt/s), in a highly processive manner. In contrast, viral RNA polymerases engaged in transcription (transcriptases), although capable of synthesizing RNA at a comparable speed to replicases, were poorly processive. In this system, therefore, transcriptases require special reaction conditions to promote processivity that are not required by replicases. In addition, during replication, incomplete nascent genome chains were shown to be assembled with N protein, providing direct evidence that the synthesis and assembly of genomes are concurrent events. The strong processivity of replicases, independent of the reaction conditions, may thus be due to the coupling of genome synthesis and assembly. A model is proposed to explain how pausing of viral polymerase on the template is restricted when assembly and synthesis of the nascent chain are coupled.
