CBD for seizures:
Can it Help? April 2024

Seizure Overview

To control the body, the brain’s billions of neurons use electrical signals to communicate and coordinate our movements.

During a seizure, neurons release a burst of disorganized electrical activity in the brain-altering muscle movements (such as stiffness, twitching, spasms), speech, behaviors, sensations, moods, thoughts, and even consciousness. ¹

Not all seizures are alike and they can be caused by a wide range of triggers such as:

• Medications, alcohol, or drugs
• Withdrawal syndromes (from alcohol, benzodiazepines, or others)
• Heart conditions or a stroke
• Infections and sepsis
• Brain injuries or brain disease
• Fevers
• Sleep deprivation
• Genetics

Apart from the wide variety of possible causes, there are also many different types of seizures.

The three major groups include focal or partial-onset, generalized onset, and unknown onset.

Focal (or Partial) Onset

Focal onset seizures take place when the abnormal electrical signals occur in just one side – or one hemisphere – of the brain. Depending on how much of the brain becomes involved, symptoms can vary from mild to severe. ²

Because only one half of the brain is affected, the individual experiencing the seizure may often notice minor symptoms before it spreads. This is referred to as an “aura” or a premonition.

This can manifest as altered feelings (such as déjà vu, fear, euphoria) and/or physical symptoms (such as changes to vision, hearing, or sense of smell).

As the seizure spreads across the brain, eventually more symptoms will appear.

Focal seizures can also be further divided into two subtypes based on how much of the brain hemisphere becomes involved:

• Focal impaired awareness occurs when the activity is limited to a smaller single region of the brain. In these instances, only certain symptoms are experienced. For example, if the activity is limited to the occipital lobe of the brain – an area that is involved with vision – sight can become altered. Typically, consciousness is not lost and the person is aware of what is happening.
• Complex focal seizures happen when a large area of the brain is affected. The person may lose awareness and experience multiple complex symptoms including altered muscle movements and behaviors.

It’s important to note that seizures can begin focally – in one side of the brain – but eventually spread to both sides and become generalized.

Generalized Seizures

Unlike focal seizures which only affect one-half of the brain, generalized seizures affect both halves more or less at the same time. Because of this, a loss of consciousness can occur. ³

Generalized seizures can be further subdivided into categories:

• Absence seizures also referred to as “petit mal seizures” are usually short (no longer than about 30 seconds) and can cause rapid blinking or face twitches. Absence seizures can occur in childhood and sometimes be outgrown.
• Tonic, clonic, and tonic-clonic seizures are also referred to as “grand mal seizures.” Tonic refers to the presence of muscle stiffening while clonic refers to periods of shaking or jerking. One or both of these conditions can happen during a seizure.
• Atonic seizures (also called drop seizures) involve the sudden loss of body tone when muscles relax which can result in the person collapsing. Before an atonic seizure, people can also experience brief tonic episodes where the muscles stiffen first.
• Myoclonic seizures involve sudden body or limb jerks. This can include sudden arm, leg, neck, or head movements.

To categorize the type of seizure, physicians and other medical professionals typically use detailed patient histories, electroencephalogram (EEG) findings, magnetic resonance imaging (MRI), computed tomography scans (CT or CAT scans), blood tests, and other information.

Unknown Onset

Sometimes, it can also be difficult to determine the seizure’s onset, and in those situations, the seizure is often referred to as having an unknown onset.

This can happen, for instance, if no one was present to witness the seizure and/or if the tests done afterward are inconclusive.

Difference Between Seizures and Epilepsy

While a seizure is usually a single occurrence, two or more unprovoked seizures may indicate epilepsy – a neurological condition. ³ ⁴

With epilepsy, the brain becomes more susceptible to having seizures. This may be due to genetic reasons (such as metabolic problems), developmental issues, or head trauma and brain infections.

Epilepsy is one of the most common neurological conditions and affects an estimated 2.2 million Americans. This disorder can significantly impair an individual’s quality of life, lead to cognitive or psychiatric disorders, or contribute to accidental fatalities such as drowning.

Treatments will vary depending on age, overall health, types of seizures, possible causes, and frequency. Most treatment options involve medication, surgery, dietary therapies, or vagus nerve stimulation (where an electrical device is implanted in the chest to stimulate the vagus nerve).

Despite the growing number of treatment options, research suggests that approximately one-third of epilepsy patients do not respond well to conventional anti-epileptic drugs, making it a major motivation for continued research into anti-seizure medications. ⁵

Can CBD Help?

CBD has been known to influence the body’s central nervous system through the endocannabinoid system (ECS) – a neural network that helps regulate a wide variety of physical and mental processes such as memory, learning, mood, pain management, and inflammation. ⁶ ⁷

The importance of the endocannabinoid systems has led to its investigation as a possible target for new anti-epileptic drugs. Many anecdotal reports beginning in the 1900s have indicated some success in using CBD to treat epilepsy – motivating additional research.

As part of the endocannabinoid system, our bodies naturally produce endocannabinoids which interact with endocannabinoid receptors on different cells and neurons. Cannabinoids from the cannabis plants, including CBD, can naturally mimic certain endocannabinoids and can modulate the way various endocannabinoid receptors work.

The most abundant receptors include CB1 and CB2. Tetrahydrocannabinol (THC) – the primary psychoactive component of cannabis – has been shown to interact heavily with both receptors which allow it to produce anticonvulsant effects. ⁸ ⁹

However, CBD interacts much less with CB1 and CB2, and the exact mechanism by which CBD triggers an anti-seizure effect remains incompletely solved.

Nonetheless, multiple animal studies have shown that CBD can have anti-epileptic properties.

In mice, CBD has been shown to protect against artificial seizures induced using electrical shocks, or drugs such as pentylenetetrazol, penicillin, and pilocarpine. ¹⁰ ¹¹

CBD reduced the number of severe tonic-clonic seizures the animals experienced and decreased mortality rates.

Instead of CB1 and CB2, CBD has instead been suggested to drive its anti-epileptic effects through interacting with many other receptors. This includes the serotonin receptor (5-HT1A receptor), GABA receptors, TRPV1 channels, NMDA receptors, and adenosine signaling. ⁹ ¹²

What Does the Research Say – Survey-Based Studies

Despite strong evidence in animal models that CBD can be anti-epileptic, studies in humans have been somewhat mixed – particularly with survey-based studies.

In 2001, information interviews with over 215 patients with active epilepsy who also used cannabis products found that 90% of participants reported not seeing any beneficial effects of cannabis in seizure control. Only 7% felt their condition improved and 3% reported their seizures were worse. ¹³

In a separate 2017 Australian study, 976 patients with epilepsy were surveyed and 15% reported using cannabis – regardless of their physician’s knowledge – to control their multi-drug resistant seizures. The majority of them reported an improvement in their condition. ¹⁴ A significantly different finding from the 2001 study.

It’s important to note that many of these survey-based studies are unable to account for dosage, frequency of use, method of administration, and other factors that may influence the effectiveness. For instance, many of these survey participants smoked whole cannabis or used both CBD and THC simultaneously alongside other drugs.

What Does the Research Say – Clinical Studies

Some clinical studies have also had mixed results while testing the efficacy of CBD in treating epilepsy.

However, most are from early studies looking only at short durations (approximately 3-4 months) with a small number of human volunteers (approximately 15). The smaller sample size makes the results less reliable and more variable. ¹⁵

In one double-blind 1980 study, researchers found that out of 8 participants who took 200-300 mg CBD, 4 of the 8 subjects remained almost free of convulsive crises during the experiment. Whereas 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient.¹⁶

In another 1990, small-scale, placebo-controlled study with 12 patients, researchers found no changes in seizure frequency between when patients were given 300 mg of CBD or a placebo. ¹⁷

Larger scale studies have only just begun in the last decade and most have only investigated the use of CBD in conjunction with other anti-epileptic drugs and in patients with treatment-resistant forms of epilepsy. These are patients with very limited treatment options.

Furthermore, most patients tend to be children, and adult patients are underrepresented in most CBD trials.

The first randomized, controlled, double-blinded, and multi-center study was done in 2015 and specifically tested the use of 20 mg per kg dose of CBD in addition to conventional anti-epileptic drugs for treating Lennox-Gastaut syndrome – a treatment-resistant and childhood-onset form of epilepsy. ¹⁸

Of 86 patients aged 2-55 who were in the CBD group, 43.9% reported a reduction in the number of drop seizures while only 21.8% of patients in the placebo group reported an improvement.

A similar randomized, double-blind, and placebo-controlled study in 2017 looked at the use of CBD as an add-on option to treat Dravet syndrome – another rare and treatment-resistant childhood-onset epilepsy. ¹⁹

61 patients aged 2 to 18 were given 20 mg per kg CBD per day. 43% of patients experienced at least a 50% reduction in convulsive-seizures after a 14-week treatment period. Out of the 52 patients that completed the treatment period, 3 patients taking CBD became completely seizure-free.

A third randomized, double-blind, placebo-controlled trial was published in 2018 again using CBD as an add-on option to treat patients with Lennox-Gastaut syndrome. 76 patients aged 2 to 55 were given 20 mg per kg CBD, 73 were given 10 mg per kg CBD, and 76 were given a placebo. ²⁰

During the 28-day period, the 20 mg per kg CBD group had a 41.9% decrease in drop seizures and the 10 mg per kg group had a 37.2% decrease. The placebo group only experienced a 17.2% decrease in seizure numbers.

In all three randomized, double-blind, and placebo-controlled trials, patients taking 20 mg per kg CBD experienced reduced seizure frequencies as compared to those who took a placebo indicating that CBD can be a useful and effective treatment option. ²¹

Furthermore, a 2017 review of 6 different randomized controlled trials and 30 observational studies found that CBD when used in combination with other anti-epileptic drugs at 20 mg per kg a day was more effective than placebo at reducing seizure frequencies. ²²

Current FDA-Approved Prescription CBD

Currently, one CBD-based drug – Epidiolex – has been approved by the Food and Drug Administration (FDA) for treatment of Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis (a genetic disease that can cause seizures).

However, similar to other research n CBD, the mechanism by which Epidiolex triggers anticonvulsant effects is unknown. The Epidiolex prescribing information reports that CBD does not appear to exert its anticonvulsant effects through interactions with the cannabinoid receptors.

A recent 2020 report proposed that Epidiolex – like other non-prescription CBD – may trigger anti-epileptic effects through targeting other brain receptors such as TRPV1, GPR55, and ENT-1. ²³

Trying CBD for Seizures

Recent clinical reports have shown that CBD can be an effective treatment option for epilepsy – specifically for patients with rare forms of epilepsy, such as Dravet and Lennox-Gastaut syndromes. But CBD is almost always used alongside other anti-epileptic drugs to achieve a consistent anti-epileptic effect – primarily clobazam. ²¹

It’s best to consult with a physician before attempting to use CBD to treat seizures or epilepsy at home. Your doctor may have you on a pharmaceutical that negatively interacts with CBD (or a product that might contain THC).

And as with using CBD for any health reasons, it’s best to begin with a low dosage and only move up as needed.

However, while CBD is generally safe and well-tolerated, at higher concentrations, it can also cause a wide range of side effects.

Some of these can include: ²⁴

• Tiredness
• Drowsiness
• Diarrhea
• Nausea
• Dry mouth
• Low blood pressure
• Light-headedness
• Changes in appetite or weight

In studies specifically examining the use of CBD in treating epilepsy, the major side effects typically observed include somnolence, diarrhea, and decreased appetite. ¹⁵

For instance, in the study performed with Lennox-Gastaut patients using CBD, 86% of participants reported at least one or a combination of those side-effects. ¹⁵

Furthermore, there are additional considerations to make when CBD is taken alongside other medications. CBD can interfere with how other drugs are metabolized and processed within the body possibly causing adverse drug reactions. ²⁵

For instance, the efficacy of clobazam – a commonly used benzodiazepine used to treat epilepsy – has been observed to be influenced by CBD.

In a systematic review of 4 different randomized, placebo-controlled clinical trials, researchers found that patients who took both CBD and clobazam were more likely to experience a reduction in seizure frequency. ²⁶

This is thought to be caused by CBD blocking the breakdown of clobazam. This may help clobazam remain active in the body for longer and exerting increased beneficial effects, but this also increases the risk of adverse reactions. ²⁷

Likewise, research has only just begun to investigate whether certain forms of CBD may be more beneficial than others.

In a recent 2018 analysis comparing the use of CBD-rich cannabis or purified CBD, researchers found that CBD-rich extracts seem to present a better therapeutic profile than CBD in patients with refractory or drug-resistant epilepsy. ²⁸

This may be due to the entourage effect – a synergistic effect of CBD when it works alongside other phytocompounds in cannabis. Although this remains to confirmed in controlled clinical studies.

Conclusion

Significant research has occurred in the past century from initial small-scale reports to large-scale clinical studies validating the use of CBD for seizures and certain forms of epilepsy.

However, studies conducted to date primarily focus on rare and drug-resistant forms of childhood-onset epilepsy – specifically Dravet and Lennox-Gastaut syndrome.

Most studies have also only focused on children and have not thoroughly investigated whether patient age, drug tolerance, or long-term risks could be at play.

Much more research is still needed to test its use in other forms of seizures and epilepsy.