February 6, 2019
Cannabis for Seizures and Epilepsy. Cannabis has been utilized as a treatment modality for seizure disorders and epilepsy, with records dating back to 10th century Persia, pouring the juice of hemp leaves intranasally to prevent seizures in children.
Cannabis is becoming increasingly proven to be a clinically significant alternative for the treatment of seizure disorders and epilepsy, particularly in children with severe, life-threatening seizure conditions like Dravet’s Syndrome.
Severe childhood seizure disorders and epilepsies are characterized by frequent seizures, neurodevelopmental delays, and impaired quality of life.
Benzodiazepines and antiepileptic medications are the primary courses of medical treatment for seizure disorders and epilepsy.
In at least 30% of cases, however, the patients’ seizures fail to be controlled anti-epileptic medications at their appropriate dosage, resulting in a diagnosis of “drug-resistant” or “refractory” epilepsy.
Dravet’s Syndrome (DS), is severe, distinctive myoclonic epileptic syndrome, characterized by acute onset, often with status epilepticus, occurring in infancy, within the first 6–18 months of life.
It is characterized by ataxia, hyperactivity, sleep disorder, cognitive deficit, autistic-like behaviors, and premature death. This form of seizure disorder is often treated with a multitude of high-dose antiepileptic medications and benzodiazepines.
These treatment modalities are often ineffective at treating this seizure disorder, resulting in more dangerous, adverse side effects for the pediatric patient. Without an appropriate course of treatment, the uncontrolled seizure activity and adverse effects of the pharmacological medication will result in death.
Recent research focuses primarily on the therapeutic properties of cannabidiol (CBD), as it delivers a range of anticonvulsant and anxiolytic effects with few adverse or intoxicating effects, Many other cannabinoids (THCV, CBDV, THC) are being studied, in both their acidic and activated forms, in clinical human trials for their relationship to seizure disorders.
According to Sulak, Saneto & Goldstein (2017), CBG is a lesser-known cannabinoid that is currently being studied for its significant anticonvulsant properties; as is linalool, a terpene common in certain cannabis cultivars and the lavender plant.
Phytocannabinoids (cannabis plant) and synthetic cannabinoids (Marinol, Epidiolex) that target and act on CB1 receptors appear to demonstrate the most significant anti-convulsant effects and are commonly utilized as a treatment modality for chronic seizures and epilepsy. Cannabis cultivars with predominantly high levels of CBD (i.e. Charlotte’s Web, Harlequin) are being effectively utilized in the form of concentrated cannabis oils for the treatment of treatment-resistant epilepsy and other seizure disorders.
In these treatment-resistant epilepsies, families often seek alternative treatments. According to a parent-survey survey exploring the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy, there was a significant reduction in or cessation of seizures, and parents described other benefits to the child’s quality of life of child including alertness, better mood, and improved sleep. (Porter & Jacobson, 2013)
The mechanism by which cannabis and cannabinoids inhibit seizure activity is a complex relationship between the cannabinoids being utilized, the various receptors upon which they act, and the individual’s complex endocannabinoid and nervous system receptor interactions. The different receptors and ion channels linked to these effects are CB1, CB2, TRPV1, GPR55, sodium and calcium channels, and many more.
The short-term side effects of cannabis use may include impairment of memory, judgment, and motor performance.
Cannabis-based treatment with high doses of Δ9-THC may have irreversible effects on brain development, cause cognitive impairment, decreased motivation, and has been associated with early-onset psychosis and schizophrenia when children consume high doses of THC. It is unknown whether adverse effects on the brain are mediated solely by psychoactive cannabinoids, such as Δ9-THC, or whether long-term exposure to CBD and other cannabinoids also have deleterious effects.
Until more data and research becomes available, the neurodevelopmental risks of cannabinoid-based therapies should be weighed against the potential benefits for seizure control and the effects of seizure activity on brain development. Many anticonvulsants and benzodiazepines are also associated with teratogenicity and neurodevelopmental impairments in children.
In an open-label trial (Devinsky et. al., 2016) patients aged 1–30 years with severe, intractable, childhood-onset, treatment-resistant epilepsy, 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. Adverse effects that occurred in more than one study included nausea, weakness, mood changes, psychosis, hallucinations, suicidal ideation, dizziness or lightheadedness, fatigue, and feeling of intoxication. No deaths from overdose were reported in association with cannabinoid-containing medications.
Anderson, L., et. al. (2017). Cannabidiol for the Treatment of Drug-Resistant Epilepsy in Children: Current State of Research. Journal of Pediatric Neurology.
Devinsky, O., et. al. (2014). Cannabidiol: Pharmacology and Potential Therapeutic Role in Epilepsy and Other Neuropsychiatric Disorders. Epilepsia, 55(6): 791-802.
Devinsky, O., et. al. (2016). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet Neurology, 15(3): 270-278.
Friedman, Daniel & Devinsky, Orrin. (2015) Cannabinoids in the Treatment of Epilepsy. The New England Journal of Medicine, 373: 1048-1058.
Kwan, P. and Brodie, M.J. (2007). Emerging Drugs for Epilepsy. Expert Opinion on Emerging Drugs, 12: 407-22.
National Academies of Sciences, Engineering, and Medicine. (2017). The Health Effects of Cannabis and Cannabinoids: The current state of evidence and recommendations for research. The National Academies Press: Washington, D.C.
Porter, B. & Jacobson, C. (2016). Report of a Parent Survey of cannabidiol-enriched cannabis use in pediatric resistant epilepsy. Epilepsy Behaviour 29(3): 574-577.
Sisodiya, Sanjay M. (2013). Epilepsy. Genomic and Personalized Medicine, 2: 1044-1050.
Sulak, D., Saneto, R., Goldstein, B. (2017). The Current Status of Artisanal Cannabis for the Treatment of Epilepsy in the United States. Epilepsy & Behaviour, 70(B): 328-333.