Publications

Scholarly Journals--Published

  • “Cannabis for Pediatric Epilepsy”Huntsman RJ,  Tang-Wai R, Shackelford AEJournal of Clinical Neurophysiology Volume 37, Number 1, January 2020, pp. 2-8.?ISSN: 0736-0258/19/3701-0002DOI 10.1097/WNP.0000000000000641 Summary: Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat. The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely D9- tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies. Cannabis- based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy. Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox–Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.All authors contributed equally to the writing, editing, and revision of this article. (01/2020)
  • Huntsman, R.J., Tang-Wai, R., Alcorn, J., Vuong, S., Acton, B., Corley, S., Laprairie, R., Lyon, A.W., Meier, S., Mousseau, D.D., Newmeyer, D., Prosser-Loose, E., Seifert, B., Tellez-Zenteno, J., Huh, L., Leung, E., Major, P., “Dosage Related Efficacy and Tolerability of Cannabidiol in Children with Treatment Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study”.  Frontiers in Neurology (2019) 10:716; https://doi.org/10.3389/fneur/2019.00716. Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 ?9-tetrahydrocannabinol (THC):CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS,Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS,Min CBD levels associated with a greater than 50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS,Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible nonlinear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day. (07/2019) (link)
  • The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: A phase 1 dosage escalation study Darren Reithmeier, Richard Tang-Wai, Blair Seifert, Andrew W. Lyon, Jane Alcorn, Bryan Acton, Scott Corley, Erin Prosser-Loose, Darrell D. Mousseau, Hyun J. Lim, Jose Tellez-Zenteno, Linda Huh, Edward Leung, Lionel Carmant and Richard J. Huntsman Citation:BMC Pediatrics 2018 18:221 Published on: 7 July 2018 AbstractBackground Initial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life. Methods Twenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects. DiscussionThis paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids. Trial registrationhttp://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827 BMC Pediatrics 2018 18:221(PDF) The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: A phase 1 dosage escalation study. https://bmcpediatr.biomedcentral.com/track/pdf/10.1186/s12887-018-1191-y (07/2018) (link)

Books and Chapters

  • "Cannabis for Pediatric and Adult Epilepsy"Richard James Huntsman, Richard Tang-Wai and Jose Tellez-Zenteno (April 8th 2019). Cannabis for Pediatric and Adult Epilepsy [Online First], IntechOpen, DOI: 10.5772/intechopen.85719. Available from: https://www.intechopen.com/online-first/cannabis-for-pediatric-and-adult-epilepsy Epilepsy is a chronic disease of the central nervous system characterized by recurrent unprovoked seizures. Up to 30% of patients continue to have seizures despite treatment with appropriate anticonvulsant medications. The presence of abnormal oscillatory events within neural networks is a major feature of epileptogenesis. The endocannabinoid system can modulate these oscillatory events and alter neuronal activity making the phytocannabinoids found in Cannabis a potential therapeutic option for patients with treatment resistant epilepsy. Many in vitro and in vivo studies have demonstrated the anticonvulsant effects of several phytocannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Several small observational studies demonstrated a favorable response to cannabis herbal extracts (CHE) containing high concentrations of CBD in children with treatment resistant epilepsy. Two large double blinded clinical trials assessing the efficacy of pharmaceutical grade CBD have also been performed in children with treatment resistant seizures in Dravet syndrome and Lennox-Gastaut syndrome. Both studies demonstrated an improvement in seizure reduction in children taking CBD as compared to the placebo groups. To date there is very limited data regarding the use of cannabis based products to treat adult patients with treatment resistant epilepsy with only one randomized double blinded placebo controlled clinical trial underway. (04/2019) (link)

Abstract

  • Insight into the mesial frontal negative motor area: The girl with a very unusual interest in having her back pattedJanette Mailo, Ryan Hung, Richard Tang-Wai Poster Presentation and Selected for Platform presentation Canadian Neurological Sciences Federation, 53rd Annual Congress, June  24 - 27, 2018Halifax, Nova Scotia, CanadaCanadian Society of Clinical Neurophysiologists / Canadian Association for Child Neurology Chair's Select Abstracts session on Wednesday June 27, 2018Citation: The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques · June 2018I was the Research Supervisor   (06/2018)