Journal ArticleDOI
Interactions between cannabidiol and commonly used antiepileptic drugs.
Tyler E. Gaston,E. Martina Bebin,E. Martina Bebin,Gary Cutter,Yuliang Liu,Jerzy P. Szaflarski +5 more
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TLDR
To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open‐label safety study.Abstract:
SummaryObjective
To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs.
Methods
In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate.
Results
Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels were seen with increasing CBD dose. Increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose were seen in adults. Except for clobazam and desmethylclobazam, all noted mean level changes were within the accepted therapeutic range. Sedation was more frequent with higher N-desmethylclobazam levels in adults (p = 0.02), and AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).
Significance
Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with CBD.read more
Citations
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Journal ArticleDOI
Cannabinoids and the expanded endocannabinoid system in neurological disorders.
TL;DR: The biology of cannabinoids, the endocannabinoid system and the expanded endoc cannabinoidoid system are outlined and the involvement in and clinical relevance of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease are discussed.
Journal ArticleDOI
A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans.
TL;DR: The paucity in data and some discrepancy in the pharmacokinetics of cannabidiol are highlighted, despite its widespread use in humans, and robust data from a variety of formulations is required.
Journal ArticleDOI
Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome.
Orrin Devinsky,Anup D. Patel,Elizabeth A. Thiele,Matthew Wong,Richard Appleton,Cynthia L. Harden,Sam M. Greenwood,Gilmour Morrison,Kenneth Sommerville +8 more
TL;DR: This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.
Journal ArticleDOI
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects
TL;DR: The safety and PK profile support twice-daily administration of CBD, and most AEs were mild in severity; none were severe or serious.
Journal ArticleDOI
Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
TL;DR: There is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes, for the first time, according to currently available information.
References
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Journal ArticleDOI
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Orrin Devinsky,J. Helen Cross,Linda Laux,Eric D. Marsh,Ian Miller,Rima Nabbout,Ingrid E. Scheffer,Elizabeth A. Thiele,Stephen Wright +8 more
TL;DR: Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive‐seizure frequency than placebo and was associated with higher rates of adverse events.
Journal ArticleDOI
The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial
Anthony G Marson,Asya M Al-Kharusi,Muna Alwaidh,Richard Appleton,Gus A. Baker,David Chadwick,Celia Cramp,Oliver C Cockerell,PN Cooper,Julie Doughty,Barbara Eaton,Carrol Gamble,Peter Goulding,Stephen Howell,Adrian Hughes,Margaret Jackson,Ann Jacoby,Mark Kellett,G. R. Lawson,John Paul Leach,Paola Nicolaides,Richard C. Roberts,Phil Shackley,Jing Shen,David F. Smith,Philip E. M. Smith,Catrin Tudur Smith,Alessandra Vanoli,Paula R Williamson +28 more
TL;DR: Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.
Journal ArticleDOI
The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.
Anthony G Marson,Asya M Al-Kharusi,Muna Alwaidh,Richard Appleton,Gus A. Baker,David Chadwick,Celia Cramp,Oliver C Cockerell,PN Cooper,Julie Doughty,Barbara Eaton,Carrol Gamble,Peter Goulding,Stephen Howell,Adrian Hughes,Margaret Jackson,Ann Jacoby,Mark Kellett,G. R. Lawson,John Paul Leach,Paola Nicolaides,Richard C. Roberts,Phil Shackley,Jing Shen,David F. Smith,Philip E. M. Smith,Catrin Tudur Smith,Alessandr a Vanoli,Paula R Williamson +28 more
TL;DR: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies, and because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.
Journal ArticleDOI
Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.
Orrin Devinsky,Maria Roberta Cilio,Helen Cross,Javier Fernández-Ruiz,Jacqueline A. French,Charlotte L Hill,Russell Katz,Vincenzo Di Marzo,Didier Jutras-Aswad,William George Notcutt,José Martínez-Orgado,Philip Robson,Brian G. Rohrback,Elizabeth A. Thiele,Benjamin J. Whalley,Daniel Friedman +15 more
TL;DR: CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic‐ischemic encephalopathy, however, data from well‐powered double‐blind randomized, controlled studies on the efficacy of pure CBD for any disorder is lacking.
Journal ArticleDOI
Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial
Orrin Devinsky,Eric D. Marsh,Daniel Friedman,Elizabeth A. Thiele,Linda Laux,Joseph Sullivan,Ian Miller,Robert Flamini,Angus Wilfong,Francis Filloux,Matthew Wong,Nicole Tilton,Patricia L. Bruno,Judith Bluvstein,Julie Hedlund,Rebecca M. Kamens,Jane Maclean,Srishti Nangia,Nilika S. Singhal,Carey A Wilson,Anup D. Patel,Maria Roberta Cilio +21 more
TL;DR: The findings suggest that cannabidiol might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy.
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