CBD-enriched medical cannabis for intractable pediatric epilepsy

Tzadok, Michal; Uliel-Siboni, Shimrit; Linder, Ilan; Kramer, Uri; Epstein, Orna; Menascu, Shay; Nissenkorn, Andrea; Yosef, Omer Bar; Hyman, Eli; Granot, Dorit; Dor, Michael; Lerman‐Sagie, T.; Ben‐Zeev, Bruria

doi:10.1016/j.seizure.2016.01.004

Cited by 195 publications

(187 citation statements)

References 21 publications

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“…Participants were given a standardized breakfast, and 15 minutes later, they were given either oral CBD (600 mg) or placebo in a double-blind fashion. This is a dose known to cause anxiolytic effects in humans and is comparable with what is used clinically (19,(37)(38)(39). Study medication consisted of capsules containing either 100 mg of CBD or excipients, which were a gift from GW Pharmaceuticals.…”

Section: Methodsmentioning

confidence: 99%

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

Jadoon¹,

Tan²,

O’Sullivan³

2017

JCI Insight

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Section: Methodsmentioning

confidence: 99%

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

Jadoon¹,

Tan²,

O’Sullivan³

2017

JCI Insight

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“…Several studies have administered oral doses (≤600 mg) of CBD to healthy participants with little to no marijuana use histories and have reported minimal side effects (Bergamaschi et al, 2011; Bhattacharyya et al, 2010; Cunha et al, 1980; Hollister, 1973; Karniol et al, 1974; Zuardi et al, 1993). Oral CBD has been tested in clinical populations (Huntington's disease, epilepsy patients) at much higher cumulative doses (e.g., 1280 mg/day; 50 mg/kg/day) with reports of somnolence, decreased appetite/weight loss, diarrhea and increased seizure in a small subset of epilepsy patients (Consroe et al, 1991; Devinsky et al, 2016; Tzadok et al, 2016). Despite the frequent statements in the media and the scientific literature that CBD is void of psychoactive effects, this has never been formally assessed – no studies have completed an abuse liability assessment, enrolled the population of interest (marijuana users) or compared CBD effects to a cannabinoid agent with known abuse liability, such as smoked marijuana, as a positive control.…”

Section: Introductionmentioning

confidence: 99%

Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers

Babalonis

Haney

Malcolm

et al. 2017

Drug and Alcohol Dependence

122

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Background Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5 hrs). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800 mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC). Results Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p<.05). However, CBD was placebo-like on all measures collected (p>.05). Conclusions Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA.

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“…It has low affinity to the CB1 (neuronal) and CB2 (found mainly in the body's immune system) receptors. [7][8][9][10] In fact, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted CBD preparations the "orphan drug" designation for use in the treatment of epilepsy in children (Dravet and Lennox-Gastaut syndromes) and neonatal asphyxia. 4 In vitro and in vivo preclinical research has shown that CBD has several potential effects on therapeutic applications: it possesses antiseizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, antitumor, antiemetic, antipsychotic, and antianxiety activities.…”

mentioning

confidence: 99%

Single‐Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology

Atsmon

Heffetz²,

Deutsch³

et al. 2017

Clinical Pharm in Drug Dev

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Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design. Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher C and 1.3-fold higher AUC compared with the oromucosal spray. T following both modes of delivery was 3-3.5 hours postdosing. CBD exhibited about a 1-hour lag in absorption when delivered via PTL101. A 10-fold increase in the dose resulted in an ∼15-fold increase in C and AUC. Bioavailability of CBD in the 10-mg PTL101 dose was 134% relative to the reference spray. PTL101 is a pharmaceutical-grade, user-friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.

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CBD-enriched medical cannabis for intractable pediatric epilepsy

Abstract: The results of this multicenter study on CBD treatment for intractable epilepsy in a population of children and adolescents are highly promising. Further prospective, well-designed clinical trials using enriched CBD medical cannabis are warranted.

Cited by 195 publications

References 21 publications

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers

Single‐Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology

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