Cannabis is one of the oldest psychotropic drugs known to humanity. Archaeological studies indicate that it has been cultivated and consumed in China since around 4000 BC . In 1839, British surgeon William O’Shaughnessy discovered the analgesic, appetite stimulating, muscle relaxant and anticonvulsant properties of cannabis, and began exploring it in a clinical setting. Cannabis was once sold openly in Western pharmacies throughout the 1800s and early 1900s, until the prohibition of alcohol was lifted, and alcohol became more prominent once again. During the 1930s, a public relations campaign by the Bureau of Narcotics set out to portray marijuana as a social menace, capable of destroying the youth of America. Following this, cannabis use was condemned in the USA, and most European countries followed suit and banned the drug in the early 1970s. However, there is more to the story, and this article will discuss the pharmacology of marijuana and the role of cannabis in modern medicine, specifically its importance in epilepsy.
The major psychoactive ingredient in cannabis is delta-9-tetrahydrocannabinol, commonly known as THC. Marijuana also contains many other cannabinoids, like cannabinol and cannabidiol (CBD), which are not believed to contribute to the psychotic effects of marijuana. In 1988, cannabinoid receptors were discovered in the central nervous system, particularly the basal ganglia, cerebellum, hippocampus, and cerebral cortex . These receptors are known as CB1 receptors. When activated, they exhibit a number of cellular effects, mainly by inhibiting release of neurotransmitters from neurons in the brain. Another type of cannabinoid receptor, CB2, is expressed in the microglia of the brain, but also throughout the gastrointestinal, immune, and peripheral nerve systems. These receptors play a crucial role in binding the body’s natural CB1 agonists, known as endocannabinoids, which have implications in learning, synaptic plasticity, appetite, and pain sensation. Several cannabinoids have proven to be effective analgesics in acute and chronic pain animal models. Two recent human studies have demonstrated that in patients suffering from chronic pain or central neuropathic pain, oral THC administration exhibits pain relief and improvement in sleep quality. Furthermore, oral use has also been shown to increase mobility, improve issues with muscle spasms, diminish pain, and enhance sleep quality in patients with multiple sclerosis .
Recently, there has been increased interest in treating epilepsy with medical marijuana. This August, CNN published a mini documentary about medical marijuana, featuring a young girl with Dravet syndrome, also known as Severe Myoclonic Epilepsy of Infancy. Children with Dravet often develop persistent epileptic seizures that lead to severe behavioural and developmental delays, movement and balance issues, delayed language and speech, growth and nutrition problems, and many other long-term conditions. The little girl featured in the documentary, Charlotte, had her first seizure when she was just three months old, and by the age of two, was declining developmentally. As a last resort, her parents gave her cannabis oil extracted from a strain of marijuana with low THC and high cannabidiol content. She now only has two to three seizures a month, an astonishing drop from 300+ each week. However, many doctors are skeptical on the benefits that marijuana could have for treating epilepsy. Long-term cannabis consumption in young people, especially toddlers, could have significant effects on their brain development. According to Dr. David Labiner, a neurologist specializing in Epilepsy at the University of Arizona, “There is limited high-quality evidence about the efficacy and virtually no data bout the safety of using marijuana or cannabinoids”. How much scientific research is there out there in regards to using cannabis for treatment of epilepsy?
Before this question can be answered, we must define epilepsy and understand what it is. Epilepsy is a diverse family of disorders that are related through an abnormally increased predisposition to epileptic seizures. As defined by the International League Against Epilepsy (ILAE), an epileptic seizure is “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain” . In North America the prevalence appears to be between 5-7 cases of recurrent unprovoked seizures per 1000 people. The definition of epilepsy requires the patient to have at least one seizure, as well as presence of an enduring alteration in the brain that increases the likelihood of future seizures. In epilepsy, drug resistance is defined as failure to stop all seizures in a patient who has had adequate trials of at least two appropriate medications. One-third of all people affected with epilepsy will be drug-resistant, which is why there is increased interest in the development of novel highly anti-epileptic medications.
Recent animal studies generally indicate anticonvulsant effects of CB1 agonists in rodent models of epilepsy [5,6,7]. Pure CBD, when injected into the body cavity of rodents, significantly reduces the percentage of animals experiencing severe seizures. It also decreases the percentage mortality of seizures . Another group found that cannabis rich with another type of cannabinoid, cannabidivarin, reduces convulsions in three different models of rodent epilepsy . These results suggest that the anti-convulsant qualities of CBD, combined with the absence of psychoactive effects, makes it a strong candidate for therapeutic use in human epilepsies. Surprisingly, there is very limited direct scientific data supporting the use of smoked marijuana or oral cannabinoids in humans with epilepsy . Only one clinical trial has been conducted, supported by a handful of case reports and personal anecdotes. This study took 8 volunteers with uncontrolled epilepsy, and administered oral CBD capsules or placebo in a double-blind, controlled study. Four out of eight subjects were convulsive free, three had partial improvements in their clinical condition, and one patient had no improvements. Of the eight volunteers receiving placebo, seven continued to have seizures while one patient had an improved condition .
The main issues with the current evidence supporting the use of cannabinoids to treat epilepsy are that they contain few subjects, with short periods of treatment, and are of generally low quality. This results in low implications for practice in medicine. Adequate clinical trials are required before any conclusions can be made regarding the effectiveness of medical marijuana in treating epilepsy. It is possible that medical marijuana trials are underfunded since funding agencies, including the government, are unwilling to support research looking into the positive effects of marijuana use. However, the anecdotal evidence, like that reported by CNN earlier this year, cannot be ignored. Cannabis could be an extremely effective way to control the occurrence of epileptic seizures at certain doses, but more research is required before any conclusions can be made.
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- Hill, T.D., Cascio, M.G., Romano, B., Duncan, M., Pertwee, R.G., Williams, C.M., Whalley, B.J. and Hill, A.J. 2013. Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism. British Journal of Pharmacology 170(3): 679-692.
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Marshal is a fourth year student at the University of Calgary majoring in Neuroscience. He is currently working on an honours thesis, studying the hypoxic effects that follow the induction of a seizure in a rat model of epilepsy. Follow The Triple Helix Online on Twitter and join us on Facebook.