Deep Dive: Prescribing Cannabis Medicines for Epilepsy

Updated: Oct 10

This 1500-word Deep Dive is made available at no cost until October 31.


A March 2022 research study entitled "Expert Advice for Prescribing Cannabis Medicines for Patients with Epilepsy—Drawn From the Australian Clinical Experience" that was published in the British Journal of Clinical Pharmacology stated the goal of developing "interim consensus advice for [medical] prescribers" and that this advice would provide "an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy."

The study's authors targeted a better understanding of the use of cannabis medicines "in pediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure, and frequency of symptom relief." They clarified their goal: "Rather than re-review the paucity of data on specific cannabinoids, this guidance was developed based on clinical practice and experience."


Understanding Epilepsy

According to the Mayo Clinic in Rochester, Minnesota, epilepsy is a "central nervous system (neurological) disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness." The famous clinic reported that this disease afflicts both males and females equally and that people from "all ethnic backgrounds and ages" can have epilepsy.


According to the Mayo Clinic, epilepsy is a "central nervous system (neurological) disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behavior."

Epileptic Seizures Vary Widely

Seizure activity, as a symptom of epilepsy, varies widely among patients. "Some people with epilepsy simply stare blankly for a few seconds during a seizure, while others repeatedly twitch their arms or legs," noted the Clinic. It stressed that a single seizure does not necessarily mean that one has epilepsy. "At least two seizures without a known trigger (unprovoked seizures) that happen at least 24 hours apart are generally required for an epilepsy diagnosis," reports the organization.

Conventional treatments for epilepsy include "medications or sometimes surgery" that are intended to control (decrease) seizure activity. "Some people require lifelong treatment to control seizures, but for others, the seizures eventually go away," reported the Clinic. It noted that some, but not all, children outgrow the condition to live disease-free adult lives.


Epilepsy Statistics

According to the World Health Organization, approximately 50 million people worldwide have epilepsy and it is one of the "most common neurological diseases." The organization noted that, from a global perspective, almost 80 percent of those with epilepsy "live in low- and middle-income countries."


"This equals approximately 3.5 million people with epilepsy in the U.S., which breaks down to three million adults and nearly half a million children."

According to the U.S. Centers for Disease Control and Prevention, about 1.2 percent of the total population in the United States has "active epilepsy." This equals approximately 3.5 million people with epilepsy in the U.S., which breaks down to three million adults and nearly half a million children. It reported that 0.6 percent of children aged 17 or younger feature active epilepsy. "Think of a school with 1,000 students—this means about six of them would have epilepsy," reported the public health service organization.


The Study

The study's authors noted that "approximately one-third of people with epilepsy are considered drug resistant to standard antiseizure medications (ASMs)." Novel approaches to achieving positive medical outcomes (the most significant metric for which is a reduction in average seizure activity) are necessary, according to the research. "Many patients are interested to know if cannabis medicines are beneficial in epilepsy, particularly when standard ASMs have failed to control their seizures," wrote the study's authors.


Evidence of CBD Reducing Seizures

The research described a "number of randomised, placebo-controlled...trials [that] have been published [that] used cannabidiol (CBD)" for a variety of types of juvenile epilepsy, including "Lennox–Gastaut syndrome, tuberous sclerosis complex, and severe myoclonic epilepsy of infancy, also known as Dravet syndrome."

Image courtesy Leafwize Naturals


Each of these studies found that "cannabinoids were more effective than placebo in reducing seizure frequency" in epilepsy patients.


Two clinical studies involved actual human participants with Lennox–Gastaut syndrome who received CBD administered at 10-20 mg/kg of body weight per day and included a control group that received only placebo (no CBD). Both studies revealed a "significant reduction in the median frequency of drop seizures, with ~42 percent reduction in the treatment group compared to ~17 percent in the placebo group."


Another clinical trial, this time for Dravet syndrome, dosed CBD at 20 mg/kg/day and "led to a reduction in convulsive seizure frequency of 39 percent compared to 13 percent in the placebo group."


CBD "led to a reduction in convulsive seizure frequency of 39 percent compared to 13 percent in the placebo group."

Multiple studies reviewed regarding CBD for tuberous sclerosis complex revealed that CBD treatment at 25 and 50 mg/kg/day "was compared to placebo, with a significant reduction in the median frequency of seizures of 49 percent in the treatment group (compared to 27 percent in the placebo group)."


Another study involved patients with focal seizures who were treated with CBDV (the varin version of CBD). "As as an add-on therapy, [CBDV] showed similar reductions in [seizure] frequency between the treated and placebo group," reported the scientific investigation, providing a more ambiguous result than the other studies cited.


Another research study in the U.S. "showed a reduction in monthly motor seizures of 37 percent after treatment of up to a maximum of 50 mg/kg/day of CBD."

The THC molecule


No Human Trial Evidence for THC

"There is no class I, II, or III evidence for the effectiveness of tetrahydrocannabinol (THC) or other cannabinoids [outside of CBD] to treat epilepsy in humans," reported the study's authors. They noted that "there is no established role in the treatment of epilepsy for any preparation other than one containing pure CBD."


This does not mean that other cannabinoids provide no benefit to epilepsy patients. It simply indicates that controlled scientific investigations in the form of clinical trials involving humans in placebo-controlled studies are required to precisely gauge the potential effectiveness of major cannabinoids other than CBD, including THC, cannabigerol (CBG), and cannabinol (CBN).


"In 2018, the U.S. Food and Drug Administration approved Epidiolex, a CBD oral solution, for epilepsy treatment."

Milestone: FDA Approves Epidiolex

In June 2018, a milestone was achieved for the use of medical cannabis for epilepsy when the U.S. Food and Drug Administration approved Epidiolex, a CBD oral solution, for the treatment of seizures "associated with rare epilepsy syndromes."


In Australia, health authorities in the country have approved the use of CBD to treat epilepsy under the trade name Epidyolex and only for patients with Lennox–Gastaut syndrome and Dravet syndrome.


Only Epidiolex & Sativex

The study reported that CBD in the form of Epidiolex (Epidyolex) and THC in the form of Sativex (nabiximols) "are the only medicines currently approved by any national government regulatory agency for medical prescription" for epilepsy. It noted that the synthetic THC cannabinoids dranabinol and nabilone have been approved for a number of nonepileptic conditions outside of Australia.


The study noted that many products are being prescribed by medical doctors in Australia and other nations to epilepsy patients that are "nonapproved and nonregulated hemp-derived products."

Hemp plants produce CBD


CBD Dosing Recommendation

As the primary purpose of the research investigation was to provide evidence-based direction to medical practitioners in the real world, the study included detailed dosing information. It noted the subjective efficacy of cannabinoids such as CBD and that patients respond in a variety of ways to them.


They recommended a daily dose of two to five mg/kg (separated into two spaced doses) that is slowly increased (titrated) "to effect whilst monitoring for side effects." The study recommended a maximum increase in CBD dose of five mg/kg/day per week.


CBD Dosing Range

"The current therapeutic dosing range of CBD is 5–20 mg/kg/day," reported the study, with a recommendation that the dose is given "in two divided doses." It explained that larger doses of up to 50 mg/kg/day have been trialed "but were associated with higher rates of adverse events." It recommended an initial target dose of 10 mg/kg/day (again, in the form of two separate doses).


"Current therapeutic dosing range of CBD is 5–20 mg/kg/day," reported the study.

The detailed research recommended dosage adjustment for patients "with moderate or severe hepatic impairment." It noted that its dosing guidelines "are for the Epidyolex product and cannot necessarily be applied to other oral CBD formulations." The scientists also reported that their results do not apply to CBD that is inhaled or applied via transdermal patch.


CBD & THC Side Effects

The research reported that its data reveal that the most common side effects of CBD consumption for epilepsy were "sleepiness, diarrhoea, decreases in appetite and weight, and drug interactions." It noted that 60 percent of trial subjects experience somnolence (the state of being drowsy or tired). However, it explained that many patients responded positively to dosage adjustments and that these reduced or removed this drowsiness.


For THC, short-term side effects reported included anxiety. Other studies have indicated that potential anxiety or paranoia may be avoided in many patients with proper dosing.


Conclusions

The study's authors took a conservative stance and recommended the use of CBD in epilepsy patients only for "drug resistant epilepsy, in carefully selected compliant patients with specific [types of] epilepsy."


The researchers declared that they had "provided general and population-/disease-specific guidance in terms of inclusion, exclusion, and product information based on clinical practice, supplemented by quality clinical trial data."


View the original study.


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