Epilepsy is a broad term for a group of conditions characterized by seizures. There are over forty different types of epilepsy and many different types of seizures. The mainstay of treatment is antiepileptic drugs (AEDs). Other treatments include a restrictive diet (called the ketogenic diet), a vagal nerve stimulator (a pacemaker-like device implanted in the chest that sends a signal to disrupt the firing of nerves), and brain surgery to remove the area of the brain that may be causing the seizures.
Approximately 47-50% of patients with epilepsy will respond to the first AED that is prescribed. Of those that do not respond to the first AED, only 13% will respond to the second AED and less than 4% respond to the third AED. This means that despite numerous new antiepileptic medications hitting the market every year, approximately 33% of these patients still do not achieve seizure control.1
A seizure is defined as “clinical manifestation of a hyperexcitable neuronal network, in which the electrical balance underlying normal neuronal activity is pathologically altered – excitation predominates over inhibition.”2 The goal of AEDs is to stop seizures by enhancing inhibition or by opposing excitation of the neuronal activity. Unfortunately, for a significant portion of the population suffering with seizures, these medications may not be effective and may have severe adverse side effects.
As you have learned, the endocannabinoid system works by maintaining homeostasis. In simple terms, it balances cells by regulating the neurotransmitters, specifically sending messages to neurons to decrease excitation and promote inhibition. There is compelling scientific evidence to suggest that dysfunction of the endocannabinoid system plays a critical role in the development of seizures:
In a review of 31 animal studies investigating the antiepileptic effects of different doses of THC, THC showed an effective anticonvulsant effect in 61% of the subjects, had no effect in 29% of the subjects and was a proconvulsant (caused seizures) in 10% of the subjects.7 Many adult patients with epilepsy report anecdotally that self-medicating with cannabis controls their seizures. I have numerous adult epilepsy patients in my medical practice that use low-dose THC-rich cannabis, either alone or in combination with an AED, who have excellent control of their seizure disorder and no reported adverse side effects. However, use of THC on a daily basis for seizure control can be quite difficult for patients who dislike the psychoactive properties. Development of tolerance to the effects may also be an issue with long-term chronic use of THC in this serious medical disorder.
Of note, in two separate instances, two of my adult patients who had never had seizures before reported to me that they experienced seizures after inadvertently overdosing on THC-rich cannabis edibles. Both patients, who were experienced cannabis users, ate an entire THC-rich candy bar that, unbeknownst to them, contained high amounts of THC (approximately 180mg). Each patient reported having a grand-mal seizure they had never experienced before or since. Both patients recovered quickly but were rightfully frightened by the experience. Although the amount of THC these patients ingested represents a THC overdose and is certainly not recommended dosing for most medical conditions, this shows that THC may have proconvulsant effects in humans at high doses.
Scientific studies documenting the antiepileptic action of cannabis in humans are limited since we have not been free to research cannabis due to its Controlled Substance Schedule I designation. Importantly, CBD has been found to show anticonvulsant activity in all animal research. With the recent barrage of media attention on medical cannabis, specifically CBD use in pediatric epilepsy, researchers have focused on CBD-rich treatment as a viable option for patients with intractable epilepsy. Here is a review of the studies that have looked at CBD treatment of epilepsy in humans:
Recent research into the antiepileptic effects of CBD has revealed that it works at numerous sites in the brain to lessen the hyperexcitable state, thereby reducing seizures. CBD has been called a “promiscuous” molecule because of its multiple mechanisms of action.
CBD has been found to:
Inflammation of the brain, called “neuroinflammation”, has been extensively researched over the last two decades, both as a cause and a result of recurrent seizure activity.17 The presence of neuroinflammation predisposes the brain to have more seizures. Research suggests that seizure-related inflammation may contribute to cell death.18 CBD is a well known potent anti-inflammatory that works to reduce inflammation that may promote or result from seizure activity. This added benefit of CBD may be why many epilepsy patients appear to have cognitive improvement in addition to an antiepileptic effect. Many CBD-rich chemovars of cannabis also contain the terpenoid beta-caryophyllene, which has potent anti-inflammatory properties and is synergistic with CBD in its anti-inflammatory effects.19
Studies have shown that CBD acts as a neuroprotective agent.20,21 Neuroprotection refers to the preservation of nerve cells, either by mechanisms that prevent cell damage or slow the progression of damage or disease. The mechanism by which CBD protects the brain is not completely understood but thought to be due to its effect on maintaining homeostasis of the flow of calcium in brain cells.22
CBD also stimulates growth of new neurons, especially in the part of the brain called the hippocampus.23,24 The hippocampus is responsible for memory, spacial navigation and emotional response. The hippocampus can be the focus of seizures and can also sustain severe damage from repeated seizures. More research is needed to learn the significance of CBD’s effects on the hippocampus, but certainly it is promising that CBD protects brain cells and encourages the growth of new neurons.
CBD is metabolized in the liver by the enzyme system called “cytochrome P450.” Many AEDs are metabolized in this system as well and drug-drug interactions can take place if both CBD and certain AEDs are present in the body at the same time. In an Epidiolex study, medications that showed blood level variation, meaning the levels were either increased or decreased after CBD was added to the medication regimen, included clobazam, valproate, levetiracetam, felbamate, lamotrigine, zonisamide, diazepam, and a number of others.25 In some cases the AED dose required adjustment so that toxicity could be avoided.
It is very important that patients who take antiepileptic medications are aware of the possible drug interactions with CBD. Patients on AEDs should be medically supervised when adding cannabis to their medication regimen.
I have evaluated many adult and pediatric patients who have suffered intractable epilepsy who are now experiencing excellent results with CBD-rich oil taken either sublingually, orally or via G-tube. Parents and patients report reduction of seizures, improved alertness, improved memory, better mood, better sleep, better appetite, improved motor skills, improved social interaction and less use of AEDs. Approximately 75% of my patients with intractable seizures who were surveyed in April 2015 after three months of CBD use reported a reduction of seizure frequency of 25% or greater, with 38% reporting greater than 50% reduction and 12% reporting seizure freedom (total of 112 patients, ages 1 year to 44 years, unpublished results 2015). Less than 5% of patients reported adverse side effects, which included diarrhea and sedation. Of the patients who achieved seizure freedom, five weaned off all AEDs without a recurrence of seizures. There were approximately 10% who either did not respond or who had worsening seizures that returned to baseline after discontinuation of CBD treatment.
Most patients begin treatment with CBD-rich medication in higher ratios (somewhere between 20:1 and 30:1), starting at a low dose and increasing every few weeks depending on results. Following levels of AEDs is recommended. Some patients add THCA to their CBD regimen for its anti-inflammatory and anticonvulsant effects; some who have not responded to CBD have responded to THCA treatment. Other patients have added low-dose THC with a result of seizure reduction. Patients in my practice have had success with CBD-rich chemovars that include Charlotte’s Web, AC/DC, Canna-Tsu, Harlequin and Cannatonic. Important anticonvulsant terpenoids include β-Carophyllene, linalool, pinene, and limonene.26
As mentioned previously, cannabis treatment is very individual and trial and error may be required to find what is effective. For patients with intractable seizures, CBD is proving to be an effective treatment, but because of drug interactions and the life-threatening nature of epilepsy, medical supervision is highly recommended if cannabis treatment is going to be used.