“Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.
Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.Category Archives: Epilepsy
Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.
“This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products.
The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis,” “cannabinoid,” “cannabidiol,” or “CBD” resulting in 199 papers.
The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months).
Two thirds of patients reported improvement in the frequency of seizures (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/223, 36%), with statistical significance (p < 0.0001).
Nevertheless, when the standard clinical threshold of a “50% reduction or more in the frequency of seizures” was applied, only 39% of the individuals were considered “responders,” and there was no difference (p = 0.56) between treatments with CBD-rich extracts (97/255, 38%) and purified CBD (94/223, 42%).
Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs. 291/346, p < 0.0001) and severe (23/285 vs. 77/346, p < 0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts.
CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.”
https://www.ncbi.nlm.nih.gov/pubmed/30258398
https://www.frontiersin.org/articles/10.3389/fneur.2018.00759/full
Cannabidiol for Treatment of Childhood Epilepsy-A Cross-Sectional Survey.
“The interest in cannabidiol (CBD) for treatment of epilepsy has been increasing over the last years. However, practitioner’s attitudes concerning the use of CBD for epilepsy treatment appears to be divided and data about its clinical use in daily practice are not available. Objective: To improve the knowledge about the current use of CBD amongst European practitioners treating children and adolescents for epilepsy. Methods: Cross-sectional survey using an open-access online questionnaire for physicians treating children or adolescents for epilepsy within eight European countries from December 2017 to March 2018. Results: One-hundred fifty-five physicians participated in the survey. CBD is increasingly used by 45% (69/155) of participants, treating a mean (range) number of 3 (1-35) with CBD. Only 48% of the participants prescribing CBD are exclusively using purified CBD to treat children and adolescents with epilepsy, the remainder also applies preparations containing delta9-tetrahydrocannabinol (THC). Reported daily CBD doses range from < 10 to 50 mg/kg body weight. Management of CBD therapy in regard of monitoring side effects and adjusting concomitant therapy differs widely amongst participants. Their primary objective for commencing CBD is improving patient’s quality of life. Participants frequently receive inquiries about CBD treatment but only 40% may actively suggest CBD as a treatment option. Of the 85 participants currently not using CBD for epilepsy treatment, 70% would consider using CBD if available in their country of practice or given the opportunity to become familiar with this treatment option. Conclusions: CBD is increasingly used by participating physicians but individual experience remains limited. There are very diverse opinions about the use of CBD to treat epilepsy in children and adolescents and widely differing views on how to manage the CBD treatment.” https://www.ncbi.nlm.nih.gov/pubmed/30258395 https://www.frontiersin.org/articles/10.3389/fneur.2018.00731/full]]>
A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.
“Both Δ9 Tetrahydrocannabidiol (THC) and cannabidiol (CBD) components of cannabis, have been shown to have anticonvulsant effects.
Cannabis oils are used to treat seizures in drug-resistant epilepsy (DRE). Recent trials provide data on dosing, side effects, and efficacy of CBD, yet there is a paucity of information on THC in epilepsy.
Primary objective was to establish dosing and tolerability of TIL-TC150 – a cannabis plant extract produced by Tilray®, containing 100 mg/mL CBD and 2 mg/mL THC- in children with Dravet syndrome. Secondary objectives were to assess impact of therapy on seizures, electroencephalogram (EEG) and quality of life.
“Cannabis sativa contains many related compounds known as phytocannabinoids. The main psychoactive and non-psychoactive compounds are Δ9-tetrahydrocannabidiol (THC) and 
“Stressful conditions affect the brain’s neurotransmission and neural pathways that are involved in seizure susceptibility. Stress alters the intensity and/or frequency of seizures.
Although evidence indicates that chronic stress exerts proconvulsant effects and acute stress has anticonvulsant properties, the underlying mechanisms which mediate these effects are not well understood.
In the present study, we assessed the role of endogenous opioids, endocannabinoids, as well as functional interaction between opioid and 
“Anticonvulsant effects of cannabidiol (CBD), a nonpsychoactive 
“This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products.
The systematic search took place in February/2017 and updated in December/2017 using the keywords “epilepsy” or “Dravet” or “Lennox-Gastaut” or “CDKL5” combined with “Cannabis”, “cannabinoid”, “cannabidiol” or “CBD” resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months).
Two thirds of patients reported improvement in the frequency of convulsive crisis (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/223, 36%), with statistical significance (p<0.0001).
Nevertheless, when the standard clinical threshold of a “50% reduction or more in the frequency of convulsive crisis” was applied, only 39% of the individuals were considered “responders”, and there was no difference (p=0.56) between treatments with CBD-rich extracts (97/255, 38%) and purified CBD (94/223, 42%).
Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs 291/346, p<0.0001) and severe (23/285 vs 77/346, p<0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts.
CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.”
“Epilepsy is a common neurologic disorder; it is estimated that ∼50 million people are affected worldwide. About one third of those patients are drug resistant, defined as failure to stop all seizures despite adequate trials of at least 2 appropriate medications. There has been an enormous interest in developing antiepileptic drugs with novel mechanisms of action. This review discusses the evidence supporting the anticonvulsant properties of cannabis in humans, focusing on