Potential clinical benefits of CBD-rich Cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis
Creators: name: Pamplona, Fabricio
name: Coan, Ana Carolina
Publisher: name: F1000Research
Year: 2017

description: Different therapies including cannabinoid compounds have become popular for treatment-resistant epilepsy in the recent years, particularly when it comes to hard-to-treat diseases, like Dravet and Lennox-Gastaut syndromes. Much of these were due to widely known clinical cases like the Charlotte Fiji and Sam Vogelstein, widely reported in media. This was the beginning of a rush of small-scale enterprises to produce "<i>Cannabis</i> oils", followed by independent initiatives of patients and patient associations, which decided to produce the "oils" by themselves. While parental reports of efficacy are available in the scientific literature, robust clinical data-driven pharmaceutical development is just recently being gathered and published. The current study systematically evaluated all the clinical data available in the scientific literature for cannabinoid treatment in treatment-resistant epilepsy in children. The aim is to shine some light on the currently controversial question <i>of whether "Cannabis-based extracts" or "purified/synthetic compounds" would be a preferential therapeutic approach. </i>Results: Systematic screening of papers in PubMed with the keywords "Dravet" "Lennox-Gastaut" and "epilepsy" combined with "Cannabis", "cannabinoid" and "child" revealed 30 papers. Out of these, 24 were not considered for the systematic review because: they didn't have abstract (13), were just opinion papers (6), reported non-clinical data (4), reported other subjects (1), ending up with 6 valid papers published from 2013 to 2016. Another recent <i>in press</i> paper was added manually (1), resulting in (7) valid references for the analysis, with mean impact factor 5.9 (2.3 - 21.8). Public data from partial RCT research reports (2) were also considered, when appropriate. Categorical data was analyzed with Fisher’s exact test. The papers report clinical observational data from 442 patients treated with CBD-enriched extracts or "purified" CBD, daily dose of 1 to 50 mg/kg, with treatment duration ranging from 3 to 12 months (avg: 6.2 mo). Sixty-six percent (292/442) of the patients reported improvement in seizure frequency. There were more reports of "improvement in seizures frequency" in CBD-enriched extracts compared to purified CBD (224/285 vs. 68/157; p&lt;0.0001). However, when a standard clinical relevant threshold of "reduction of 50% in seizures frequency" is considered, only 40% of the individuals are considered responders and there is no difference between treatments (64/168 vs. 65/157, p=0.57). Although either treatment yielded equivalent efficacy, CBD-enriched extracts patients reported significantly smaller daily oral doses, on average 7.1 mg/kg/day vs. 22.9 mg/kg/day for purified CBD. Curiously, as far as this data is considered, there was a superior efficacy (regardless of treatment) for Dravet syndrome (37/72, p=0.01), but not for Lennox-Gastaut syndrome (78/188, p=0.18), compared to the number of responders with refractory epilepsy in general (107/305). When it comes to adverse effects report, there is also a major advantage for CBD-enriched extract over purified CBD for both light (109/285 vs. 291/346, p&lt;0.0001) and serious (23/285 vs. 77/346, p&lt;0.0001) adverse effects. Importantly, these are all adverse effects reported and specific drug-related adverse effects could not be sorted out. In conclusion, the meta-analysis suggests that treatments using CBD-enriched extracts have higher potency and a better side effects profile (but not higher efficacy) than purified CBD, at least for this group of treatment-resistant epilepsy patients. The current lack of standardization of <i>Cannabis</i>-based extracts doesn't allow one to infer about the characteristics of the product that renders these therapeutic advantages, but they are probably related to additional compounds available in the extracts (other than CBD) that may interact synergistically. Well-controlled studies with standardized <i>Cannabis</i> extracts are needed to confirm these observations.