Abstract
The objective of this observational study was to evaluate the efficacy of medical
cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1–20 years)
with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC
ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six
Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d.
Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There
was no statistically significant difference in response rate among various epilepsy
etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and
higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse
reactions were reported in 46% of patients and were the main reason for treatment
cessation.
Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen
of patients with refractory epilepsy may result in a significant reduction in seizure
frequency according to parental reports. Randomized controlled trials are necessary
to assess its true efficacy.
Abbreviations:
CBD (Cannabidiol), AEDs (Anti-epileptic drugs), ARs (Adverse reactions)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Intractable epilepsy: management and therapeutic alternatives.Lancet Neurol. 2008; 7: 514-524
- Patients with refractory seizures.N Engl J Med. 1999; 340: 1565-1570
- Chemical constituents of marijuana: the complex mixture of natural cannabinoids.Life Sci. 2005; 78: 539-548
- Chronic administration of cannabidiol to healthy volunteers and epileptic patients.Pharmacology. 1980; 21: 175-185
- The structure of cannabidiol.Tetrahedron. 1963; 19: 2073-2078
- Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice.Eur pharmacol. 1982 Sep; 24: 293-298
- Cannabidiol displays ant epileptiform and anti-seizure properties in vitro and in vivo.J Pharmacol Exp Ther. 2010; 332: 569-577
- Cannabinoids and epilepsy.Neurotherapeutics. 2015; 12: 747-768
- Endocannabinoids block status epilepticus in cultured hippocampal neurons.Eur J Pharmacol. 2007; 8: 52-59
- Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.Br J Pharmacol. 2013 Oct; 170: 679-692
- Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.Seizure. 2012 Jun; 21: 344-352
- Adverse health effects of marijuana use.N Eng J Med. 2014; 370: 2219-2227
- Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.Neuroscience. 1998 Mar; 83: 393-411
- Molecular neurobiology of the cannabinoid receptor.Int Rev Neurobiol. 1996; 39: 197-221
- International union of pharmacology. XXVII. Classification of cannabinoid receptors.Pharmacol Rev. 2002; 54: 161-202
- Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture.Mol Pharmacol. 1999; 55: 8-13
- Assessment of the role of CB1 receptors in cannabinoid anticonvulsant effects.Eur J Pharmacol. 2001; 428: 51-57
- Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.Proc Natl Acad Sci USA. 1989; 86: 9584-9587
- Agonistic properties of cannabidiol at 5-HT1a receptors.Neurochem Res. 2005; 30: 1037-1043
- The orphan receptor GPR55 is a novel cannabinoid receptor.Br J Pharmacol. 2007; 152: 1092-1101
- Random thoughts and queries on the botany of cannabis.in: Joyce C.R.B. Curry S.H. The Botany and Chemistry of Cannabis. J & A Churchill, London1970: 11-38
- Toward drugs derived from cannabis.Naturwissenschaften. 1978; 65: 174-179
- Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.Epilepsy Behav. 2013; 29: 574-577
- Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.Lancet Neurol. 2016; 15: 270-278
- CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience.Seizure. 2016; 35: 41-44
- Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox-Gastaut syndrome.Epilepsy Behav. 2015; 47: 138-141
- Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.Epilepsy Behav. 2015; 45: 49-52
- Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox-Gastaut syndrome (LGS): results of a multi-center, randomized, double-blind, placebo controlled trial (GWPCARE4).AAN Annual Meeting. 2017
- Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.Epilepsia. 2015; 56: 1246-1251
- Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs.Epilepsia. 2017; 58: 1586-1592
- Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.Epilepsia. 2016; 57: 1617-1624
- Trial of cannabidiol for drug-resistant seizures in the dravet syndrome.N Engl J Med. 2017; 376: 2011
- Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study.Brain Res. 1993; 9: 293-302
- Cannabinoid tolerance and dependence: a review of studies in laboratory animals.Pharmacol Biochem Behav. 2005; 81: 300-318
- Single-dose kinetics of deuterium-labelled cannabidiol in man after smoking and intravenous administration.Biomed Environ Mass Spectrom. 1986; 13: 77-83
- Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.Epilepsia. 2014; 55: 791-802
- Human Cannabinoid pharmacokinetics.Chem Biodivers. 2007; : 1770-1804
- Cannabidiol is a partial agonist at dopamine D2 high receptors, predicting its antipsychotic clinical dose.Transl Psychiatry. 2016; 6: e920
- Placebo and nocebo responses in drug trials of epilepsy.Epilepsy Behav. 2015; 43: 128-134
Article info
Publication history
Published online: April 16, 2018
Accepted:
March 28,
2018
Received in revised form:
March 15,
2018
Received:
November 18,
2017
Identification
Copyright
© 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
