cbd and epilepsy

Epilepsy, one of the most common nervous system disorders affecting people of all ages, is a neurological condition characterized by recurrent seizures. Treatment for epilepsy includes anti-seizure medications and diet therapy, such as forms of the ketogenic diet. Surgery may be an alternative treatment, especially when medications or diet fail to control seizures, or if drug side effects — including dizziness, nausea, headache, fatigue, vertigo and blurred vision — are too difficult for a patient to tolerate.

Caregivers of patients currently using CBD products reported significantly less burden and stress, compared with caregivers in the control group (13% less).

Vandrey says further research is needed to understand how these findings can best be applied to helping people with epilepsy. In the interim, he says, patients should consult with their physician before trying CBD products.

For their evaluation, the researchers analyzed data gathered between April 2016 and July 2020 from 418 participants — 230 women and 188 men — with 205 (49%) at least age 18 and 213 (51%) age 18 or younger. The participants included 71 adults with epilepsy who used artisanal CBD products for medicinal purposes and 209 who were caregivers of children or dependent adults to whom artisanal CBD products were given. The control group consisted of 29 adults with epilepsy who were considering the use of CBD products and 109 caregivers who were considering it for a dependent child or adult patient.

Importantly, 27 patients in the control group at the start of the study started using artisanal CBD products later in the study. After starting CBD, these patients reported significant improvements in physical and psychological health, as well as reductions in anxiety and depression.

Dravet syndrome (severe myoclonic epilepsy of infancy) is a rare, severe, childhood-onset, epileptic encephalopathy. Most patients with DS have a loss-of-function mutation in the voltage-gated sodium channel α1 gene (SCN1A gene); most of them are de novo mutations. Dravet syndrome is characterized by prolonged seizures, often triggered by fever or other quick changes in body temperature. The seizure burden is high with different seizure types such as focal or generalized seizures (absences, tonic atonic, myoclonic, tonic-clonic) and status epilepticus. Psychomotor delay and behavioral disturbances are common. The first randomized, double-blind, placebo-controlled trial of CBD in DS (GWCARE1b) was carried out in 120 children and adolescents using 20 mg/kg/day of CBD. Efficacy was assessed by comparing a 14-week treatment period with a baseline period. The median reduction in convulsive seizures was 38.9% vs 13.3% (adjusted median difference 22.8, p = 0.01). Responder rates were 42.6% vs 27.1% (p = 0.08) for convulsive seizures. For all seizures, the adjusted median difference was 19.2%, being significant (p = 0.03). Adverse events occurred often in the CBD group (93%) as well as in the placebo group (75%), most of the AEs were moderate or mild. Serious AEs were more common in the CBD group (16% vs 5%). Common side effects were somnolence (36% vs 10%), diarrhea (31% vs 10%), decreased appetite (28% vs 5%), and fatigue (20% vs 3%). The withdrawal rate was higher as well (13% vs 2%) [14]. A second double-blind, placebo-controlled, randomized trial investigated 10 and 20 mg/kg/day of CBD (GWPCARE2) in 199 children and adolescents using a similar protocol. Median convulsive seizure reduction was 48.7% in the CBD 10-mg/kg/day group; 45.7% in the 20-mg/kg/day group; and 26.9% in the placebo group. Responder rates were 43.9%, 49.3%, and 26.2%, respectively. Adverse events were common in all groups (87.5%, 89.9%, and 89.2%), 92% of the AEs were judged to be mild or moderate. The most common side effects were decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. A higher incidence of AEs, such as somnolence, rash, and pneumonia, was found when co-medicating with clobazam (CLB). Liver enzyme elevation (more than three times) was found in 12% of the CBD-treated patients, all of them in co-medication with valproate [15].

Over the past few years, the interest in using CBD for general well-being as well as a treatment option for different diseases has risen. This deluge of personal experiences and reports has inspired patients with epilepsy and their families to try CBD for seizure control. A famous report detailed the treatment course of a 5-year-old girl with Dravet syndrome (DS) who experienced up to 50 bilateral tonic-clonic seizures per month. She experienced a > 90% reduction in seizures with CBD-rich cannabis treatment. This attracted immense attention and raised the interest in treating patients with epilepsy with CBD [10]. Because of a massive amount of media reporting and the expectations and wishes of severely affected patients with epilepsy, the demand for medical cannabis and CBD treatment increased dramatically [11]. In the USA, because of the legal restrictions of cannabis and its compounds, some families even moved to other states with easier access to medical cannabis and CBD to receive this treatment for their children with epilepsy [12].

Epilepsy is clinically defined as a syndrome of recurrent unprovoked seizures, or as one seizure with evidence of an increased risk of seizure recurrence of > 60% over the next 10 years [1]. With a prevalence of 0.5–1%, epilepsy is one of the most common neurological diseases. Up to 30% of patients with epilepsy do not achieve seizure freedom with two appropriately chosen antiseizure drugs, hence, have to be considered as drug resistant. Unfortunately, recently developed new-generation antiseizure drugs have not resulted in a significantly higher rate of seizure-free patients, even though the tolerability and interaction profile of newer antiseizure drugs is, generally, more favorable [2, 3]. Seizures, as well as the side effects from antiseizure drugs, co-morbidities, and social consequences of seizures lead to a significant loss in the quality of life for those affected. Therefore, the search for new therapies is still a major challenge for patients and physicians.

First Cannabidiol Treatment in Epilepsy

As a result of the above-mentioned studies, the first plant-derived, purified, pharmaceutical-grade CBD treatment (Epidiolex ® ) was approved for DS and LGS by the US Food and Drug Administration in 2018 and for the same epilepsy entities in combination with CLB by the European Medicines Agency (Epidyolex ® ) in 2019. In 2020, approval for the treatment of patients with TSC with plant-derived, purified, pharmaceutical-grade CBD (Epidiolex ® ) was given by the Food and Drug Administration only for a maintenance dose of 25 mg/kg/day as a higher dose showed a negative risk-for-benefit ratio (see Table ​ Table1 1 for an overview of all studies).

Anecdotal reports addressing the successful seizure treatment of severe epilepsies with cannabidiol (CBD) have increased both public interest and academic research. Placebo-controlled, randomized, controlled trials proved the efficacy of pharmaceutical-grade CBD in epilepsy treatment, thus leading to pharmaceutical-grade CBD approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of seizures in Dravet syndrome and Lennox–Gastaut syndrome as well as for tuberous complex syndrome by the Food and Drug Administration only. However, the CBD market is confusing because an array of products of different origins, purity, and concentration is available. Additionally, the results from the pivotal studies with plant-derived, pharmaceutical-grade CBD cannot simply be transferred to other epilepsy types or CBD of any origin. Because of the high demands and expectations that patients with epilepsy and their caregivers have regarding CBD, information outlining the proven facts and potential risks is essential. The aim of this article is to thoroughly review available research data and practical recommendations to provide the treating physician with the necessary information for counseling patients with epilepsy.

Since the last century, the anticonvulsant effects of cannabis have been anecdotally described in small studies of patients with refractory epilepsies [6]. However, the effect of medical cannabis on seizures and epilepsies is, in general, inconsistent. The scientific work-up of the phytocannabinoid CBD has shown promising anticonvulsant effects in different animal models [7, 8]. The mechanism of action of CBD is still not fully understood. However, modulation of intracellular Ca2 + mobilization (by GPR55 and TRPV1) as well as modulation of adenosine-mediated signal pathways seem to play an essential role [9].


Four randomized, controlled, double-blind studies were carried out in childhood-onset epilepsies: two in Lennox–Gastaut syndrome (LGS) and two in patients with DS. All of them used plant-derived, pharmaceutical-grade CBD from the same company.

Lennox–Gastaut syndrome is an epileptic encephalopathy characterized by severe cognitive impairment, multiple seizures types, and abnormal electroencephalogram patterns with slowing and slow-spike and wave complexes. The incidence is about two per 100,000 and the etiology varies. The seizure burden is high and most of the patients experience drop attacks, which are a major problem because of the injury risk. Two phase III studies were carried out in patients with LGS with a focus on drop seizures. Included were 225 patients in the GWPCARE3 study, randomized to CBD 10 mg/kg/day, CBD 20 mg/kg/day, and placebo groups, all of whom were severely affected with a median frequency of more than 80 per 28 days for drop seizures and higher than 160 for all seizures. About half of the patients took CLB as a co-medication. Over a 14-week treatment period, a significant reduction in drop seizures was found between the 10-mg/kg/day group (37.2%), 20-mg/kg/day group (41.9%), and the placebo group (17.2%) reaching significance; results are significant for all seizures (36.4% vs 38.4% vs 18.5.%), but not for non-drop seizures (61.1% vs 54.6% vs 34.3%). Responder rates for drop seizures were significant (36% vs 39% vs 14%). Adverse events frequently occurred in all groups (84% vs 94% vs 72%), but most of the AEs were rated mild to moderate. Common AEs were somnolence, decreased appetite, and diarrhea; however, the number of patients who withdrew from the study because of AEs was low (1.5%, 7.3%, 1.3%) [16]. A similar study, GWPCARE4, was carried out in 171 patients, 86 in the CBD 20-mg/kg/day group and 85 in the placebo group. The primary endpoint was the mean reduction in drop seizures, which was significant (43.9% vs 21.8%, p = 0.0135). Adverse events occurred often (86% in the CBD group vs 69% in the placebo group) with diarrhea, somnolence, pyrexia, decreased appetite, and vomiting being the most common. Withdrawal from the study because of AEs occurred more frequently in the CBD group (14%) vs 1% in the placebo group [17].