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
BACKGROUND: The endocannabinoid 2-arachidonoyl glycerol (2-AG) undergoes spontaneous isomerization to biologically inactive 1-AG. This effect has not been adequately addressed in previous studies that reported 2-AG concentrations in biological samples. METHODS: Liquid chromatography tandem-mass spectrometry (LC-MS/MS) was used for 1-AG and 2-AG analyses. RESULTS: Identical collision-induced disintegration spectra were found for 1-AG and 2-AG. For specific detection of both compounds, which share a common mass transition, baseline chromatographic separation is mandatory, even when applying MS/MS technology with its generally high detection specificity. When using standard chromatographic conditions with the very short run times typically used in LC-MS/MS methods, co-elution of 2-AG with 1-AG, which is present in human serum, causes false 2-AG results. CONCLUSIONS: Our data highlight that the analytical specificity of MS/MS can be limited by interference from isobaric isomers with identical disintegration patterns. The specificity of this technology must be carefully evaluated for each individual application.
