Cannabinoids and Epilepsy

1. Cannabis and epilepsy:

An ancient treatment returns to the fore. Russo EB(1). Author information: (1)PHYTECS, 1875 Century Park East, Suite 2250, Los Angeles, CA 90067, USA.

Cannabis has been associated with the treatment of epilepsy throughout history, and if ancient Assyrian sources referring to "hand of ghost" are considered credible, this relationship may span four millennia. A tradition of usage continued in Arabic medicine and Ayurvedic practice in India, which led, in turn, to early experiments in Europe and North America with "Indian hemp." Lack of standardization, bioavailability issues, and ultimately prohibition were all factors in cannabis-based medicines failing to maintain mainstream usage in seizure treatment, but investigation was resumed in the 1970s with interesting signals noted in both laboratory and clinical settings.
Early case studies showed promise, but lacked sufficient rigor. Resumption of research coupled with mass experimentation by families of epilepsy patients has led to intense interest in cannabis-based medicines for its treatment once more, with greatest focus on cannabidiol, but additional investigation of tetrahydrocannabinol, tetrahydrocannabinolic acid, and other phytocannabinoids.

This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.


2. Recent advances in status epilepticus. Trinka E(1), Brigo F, Shorvon S. Author information: (1)aDepartment of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University bCentre for Cognitive Neuroscience, Salzburg, Austria cDepartment of Neurological, Biomedical and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona dDepartment of Neurology, Franz Tappeiner Hospital, Merano, Italy eUCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.

PURPOSE OF REVIEW: This review discusses advances in the understanding of the mechanisms of status epilepticus and its current treatment approaches. Many of these have been topics at the 5th London-Innsbruck Colloquium on status epilepticus 2015.

RECENT FINDINGS: A new definition and classification of status epilepticus was proposed, which is expected to improve treatment and stimulate research. A better understanding of the failure of seizure suppressing mechanisms and the initiation of self-sustaining seizures begins to translate into the clinical arena. Drugs, such as allopregnanolone, cannabinoids, sec-butylpropylacetamide and valnoctamide, may better target these seizure-perpetuating mechanisms. The concept of combinatorial treatments has further developed, but yet trials in humans are lacking. A new prognostic outcome-score and electroencephalography-criteria for nonconvulsive status epilepticus are ready for clinical use. Alternative routes, such as intranasal or buccal, have been explored in a number of trials suggesting that intramuscular midazolam is at least as effective as intravenous lorazepam and buccal or intranasal midazolam is at least as effective as rectal diazepam.

SUMMARY: Despite progress in basic science, translation into the clinical field remains difficult. There is hope, that the two large phase III studies in the established and refractory status that started recruitment in 2015 will better inform the clinicians in this emergency situation.


3. Cannabidiol oil in the treatment of super refractory status epilepticus. A case report. Rosemergy I(1), Adler J(2), Psirides A(3). Author information: (1)Department of Neurology, Wellington Regional Hospital, Wellington, New Zealand. (2)Department of Palliative Care, Wellington Regional Hospital, Wellington, New Zealand. (3)Department of Intensive Care Medicine, Wellington Regional Hospital, Wellington, New Zealand. 


4. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure. Hosseinzadeh M(1), Nikseresht S(1), Khodagholi F(1,)(2), Naderi N(1,)(3), Maghsoudi N(4,)(5). Author information: (1)Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (2)NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (3)Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (4)Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (5)NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model. 


5. Marijuana: a time-honored but untested treatment for epilepsy. McLachlan RS(1). Author information: (1)Department of Clinical Neurological Sciences,Western University,London,Ontario,Canada. The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures. However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done. Proper dosage and means of administration remain unknown. Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy.
This is a review of this topic from a Canadian perspective.