To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome.
Patients aged 4–10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N-desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol). Safety assessments were clinical laboratory tests, physical examinations, vital signs, ECGs, adverse events (AEs), seizure frequency, and suicidality.
Thirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC 0–t). CBD did not affect concomitant AED levels, apart from an increase in N-CLB (except in patients taking stiripentol). The most common AEs on CBD were pyrexia, somnolence, decreased appetite, sedation, vomiting, ataxia, and abnormal behavior. Six patients taking CBD and valproate developed elevated transaminases; none met criteria for drug-induced liver injury and all recovered. No other clinically relevant safety signals were observed.
Cognitive and Behavioral Neurology; Oxford University Press, 2002 Epilepsy: Patient and Family Guide, Demos Press, 2008 Alternative Therapies for Epilepsy, Demos Press, 2012 Epilepsy In Children, Demos Press, 2015
Scientific Advisory Board for Pairnomix, Egg Rock, and Tilray. Principal Investigator, North American SUDEP Registry and Sudden Unexplained Childhood Death Registry and Research Collaborative
Ongoing Support NIH U01 NS090407 (PI: S. Lhatoo) 09/30/14 ? 7/31/2019 Center for SUDEP Research: Autonomic and Imaging Biomarkers of SUDEP The principal aim is to identify the central mechanisms and markers of autonomic and respiratory dysfunction that underlie the fatal scenario in SUDEP, and thus, provide insights into potential interventions. Role: Co-Investigator NIH U01 NS090415 (PIs: M. Thom, O. Devinsky) 9/30/14 ? 7/31/2019 Center for SUDEP Research: The Neuropathology of SUDEP: The central autonomic network, serotonin and adenosine The proposed studies will leverage the world?s largest collection of SUDEP brains to explore the role of specific histopathological and biomolecular abnormalities in the brain, focusing on critical brainstem regions and the neurotransmitters serotonin and adenosine. Role: PI National Center for Chronic Disease Prevention and Promotion U48 DP 005008-01S4 (PIs: T. Spruill, O. Devinsky) 9/1/2014 ? 8/31/2019 Managing Epilepsy Well: Adapting Project UPLIFT for Hispanic Adults with Epilepsy This project proposes to translate and culturally tailor Project UPLIFT for Hispanic patients, then test and disseminate the Spanish version. Project UPLIFT is an evidence-based intervention that incorporates cognitive behavioral and mindfulness techniques to reduce depression in adults with epilepsy. Role: Co-Investigator NIH R01 EB 018308 (PIs: K.T. Block, H. Chandarana) 9/1/2014 - 8/31/2019 Comprehensive Motion-Robust Pediatric MR Imaging Using Radial Acquisitions The proposed project aims to develop novel motion-robust magnetic resonance imaging techniques and evaluate them in clinical studies for imaging of pediatric patients with Tuberous Sclerosis. Role: Co-Investigator
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funding for travel to international tuberous sclerosis research conference (from TS Alliance), and for travel to give talks at Australia TS conference (from TS Australia), and travel to cannabinoid meetings (from GW Pharma), and for travel to serve as faculty at the Penry epilepsy courses and Neuroresident scholar program.
1. GW Pharma 2. Esai Pharmaceuticals 3. Novartis Pharmaceuticals 4. Zogenix pharmaceuticals 5. Aquestive pharmaceuticals
SHIRE: Non-profit entity (April 2014) NOVARTIS: Advisory Board Member (Expert Opinion): single meeting and single honorarium received (June 2016) GW DSMC member: from 2016 and on-going; fees for work carried out for this work
EISAI: Single honorarium for a presentation at a satelllite symposium in a scientific meeting (January 2014)
a) 'Management of Brain-injured Children'; second edition; Oxford University Press; 2006 b) 'Epilepsy: The Facts'; third edition; Oxford University Press; 2009 c) 'Childhood Epilepsy: Management from Diagnosis to Remission'; Cambridge University Press; 2011
I am listed as an External Professional Advisor for the British Government's All-Party Healthcare Ombudsman regarding complaints from the British public about NHS treatments. This involves providing expert Reports which are remunerated at a fixed fee
1-Greenwich Biosciences (US affiliate of GW Pharmaceuticals) 2-Vice President of Clinical Sciences 3-Since April of 2014
1-Greenwich Biosciences (GW Pharmaceuticals) stock options exercised in May, 2017. 2-Plan to exercise remaining Greenwich Biosciences options in 1H18.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed at links.lww.com/WNL/A307.
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