Cannabis vs. Lennox-Gastaut syndrome

Positive results published in NEJM for clinical trial of Epidiolex in LGS

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BOHEMIA, N.Y.—The New England Journal of Medicine (NEJM) recently published positive results from a clinical trial of cannabidiol in Lennox-Gastaut syndrome (LGS). Cannabidiol (CBD), a compound derived from the cannabis plant that does not produce a “high,” has been an increasing focus of medical research in epilepsy. New study results from the clinical trial of Epidiolex, the lead cannabinoid product candidate for GW Pharmaceuticals, indicate that the compound significantly reduced the number of seizures in patients with LGS.
Lennox-Gastaut syndrome is a rare and severe form of childhood-onset epilepsy that typically persists into adulthood. Despite currently available medications and a polytherapy approach to treatment, most individuals with LGS will continue to have lifelong, debilitating seizures.
The results of the study published in NEJM compared two doses of CBD to placebo. Researchers reported a 41.9-percent reduction in “drop seizures” for those taking a 20 mg/kg/d regimen and a 37.2-percent reduction in drop seizures in those on a 10 mg/kg/d regimen. Drop seizures are a type of seizure that results in a loss of muscle control and often leads to falls.
Researchers enrolled 225 patients ages 2 to 55 with LGS across 30 international sites in a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of cannabidiol in patients. Side effects were reported in 94 percent of the patients in the 20 mg CBD group, 84 percent in the 10 mg group, and 72 percent of those taking the placebo. Side effects were generally reported as mild or moderate in severity and included sleepiness, decreased appetite, diarrhea, upper respiratory infection, fever, vomiting, nasopharyngitis and status epilepticus.
“This landmark study provides data and evidence that Epidiolex can be an effective and safe treatment for seizures seen in patients with Lennox-Gastaut Syndrome,” said Dr. Anup Patel, chair of the LGS Foundation’s professional advisory board, chief of neurology at Nationwide Children’s Hospital and the study’s co-first author says,
Added Christina SanInocencio, executive director of the LGS Foundation: “LGS is devastating. While it is rare to achieve complete seizure control in this patient population, we sincerely hope that more safe and effective treatment options become available so that patients and their families can have relief from unrelenting seizures.”
In other, unrelated news of cannabis extracts and journal publications, Phytoplant Research S.L. participated in a first-ever pioneering collaborative project to investigate the ability of cannabinoid cannabigerol (CBG), the molecular precursor of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). The study investigated the ability of the above to modulate the affinity and functionality of type-1 and type-2 cannabinoid receptors (CB1 and CB2, respectively) and CB1–CB2 heteroreceptor complexes. It concluded that CBG significantly modulates CB2R- and CB1R/CB2R-mediated endocannabinoid action, while the effects are weak in CB1R-expressing cells.
The results of this research, published in the journal Frontiers in Pharmacology, suggest that CBG, a non-psychotropic phytocannabinoid, at nanomolar concentrations, is capable of acting as a competitive partial agonist of the CB2R. Regarding its action on CB1R, it is not possible to rule out a potential allosteric action, since the blocking of intracellular signalling of CB1R agonists occurs at concentrations of CBG lower than those necessary for its binding to the orthostatic site of the receptor.
These findings, the company says, “reopen the discussion” about the ability of other phytocannabinoids to bind directly to cannabinoid receptors as Δ9-THC does. In the study, researchers obtained results using different approaches that include the classic radioligand ligand binding, new fluorescent-based binding techniques and the measurement of signaling pathways. In these assays, CBG was able to modify the affinity and activity of selective CB1R and CB2R agonists at concentrations with physiological relevance (nanomolar).
The results also suggest that the partial agonism on the CB2R is regulated by the presence of the CB1R. However, more complex alternative scenarios cannot be ruled out as CBG may act on the orthosteric site of the CB1R protomer and as protean agonist of the CB1R protomer within the CB1R/CB2R heteromer.
"With these findings, we demonstrate clearly that CBG is active at the cannabinoid receptors CB1 and CB2 and that it exerts its effects through those receptors. We have deepened the knowledge about phytocannabinoids and reopened the discussion about the interaction between the Cannabis plant compounds," said Dr. Xavier Nadal, director of the R&D–Extraction Department at Phytoplant Research, noting that the findings also point to significant potential for therapeutic uses of such compounds.

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