CBD for Epilepsy: The Current State of Research and Treatment

Updated January 2025: Since our original 2020 article, the landscape of CBD treatment for epilepsy has evolved significantly, with expanded FDA approvals, long-term safety data, and major clinical trials providing unprecedented insights into cannabidiol's therapeutic potential.

What is Epilepsy

Epilepsy is a neurological disorder characterized by abnormal brain activity patterns that cause seizures, unusual sensations, emotions, and behaviors. It can range from benign to life-threatening conditions, affecting people of all ages, sexes, races, and ethnicities.

Typically, at least two unprovoked seizures are required for an epilepsy diagnosis. Approximately one third of epilepsy patients do not become seizure free with antiseizure medications, creating a significant treatment gap that motivates research for new therapeutic options like cannabidiol (CBD).

Types of Seizures

Seizures are broadly categorized into two main types:

Focal Seizures (Partial Seizures)

Focal seizures without loss of consciousness: These can alter emotions or senses, causing changes in how things look, smell, taste, feel, or sound. They may also cause muscle spasms or involuntary jerking.
Focal seizures with impaired awareness: These cause change or total loss of consciousness, with symptoms like staring into space or repetitive movements.

Generalized Seizures

Absence seizures: Cause staring into space with subtle body movements, most common in children
Tonic seizures: Cause muscle stiffening, often leading to falls
Atonic seizures: Cause complete loss of muscle control and sudden collapse
Clonic seizures: Cause repeated muscle jerking
Myoclonic seizures: Cause sudden jerks or twitches
Tonic-clonic seizures: The most severe type, causing loss of consciousness, muscle stiffening, and body shaking

Current Epilepsy Treatment Options

While there is no cure for epilepsy, several treatment approaches focus on seizure control and symptom management:

Pharmaceutical Interventions

Anti-epileptic drugs (AEDs) are the most common treatment, working by changing brain chemical levels to reduce seizure frequency and severity. Common AEDs include sodium valproate, carbamazepine, lamotrigine, levetiracetam, and topiramate. While effective in about 70% of patients, AEDs often cause side effects including drowsiness, irritability, nausea, headaches, and tremors.

Non-Pharmaceutical Interventions

When medications fail, other options include:

Epilepsy surgery: Removing the brain area causing seizures
Ketogenic diet: High-fat, low-carbohydrate diet that may reduce seizures
Vagus nerve stimulation (VNS): Electrical device implanted under the skin
Deep brain stimulation (DBS): Wires placed directly into the brain

CBD & Epilepsy: The Evolution Since 2020

FDA Approvals and Regulatory Updates

The first plant-derived, purified pharmaceutical-grade cannabidiol (CBD) medication, Epidiolex, was approved in the United States by the FDA on June 25, 2018 for patients ≥ 2 years of age with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS).

Major Update: In 2021, the FDA approved Epidiolex for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older, expanding the approved indications for CBD-based epilepsy treatment.

EPIDIOLEX has received regulatory approval in numerous countries, including the U.S. (FDA), Europe (European Commission), Great Britain (MHRA), Australia (Therapeutic Goods Administration), Switzerland (Swissmedic), Israel (Ministry of Health), and New Zealand.

What Makes CBD Different

CBD differs from other cannabis derivatives because of its consistent efficacy and lack of a psychoactive effect. Unlike THC (tetrahydrocannabinol), which causes the "high" associated with marijuana, CBD is non-psychoactive and has shown more consistent antiepileptic effects.

How CBD Works: Updated Mechanisms of Action

While the mechanism of action of CBD underlying the reduction of seizures in humans is unknown, CBD possesses affinity for multiple targets, across a range of target classes, resulting in functional modulation of neuronal excitability.

Current research suggests CBD works through several pathways:

Primary Mechanisms

TRPV1 Receptors: Transient receptor potential vanilloid type 1 (TRPV1)-mediated signaling may be the most relevant pathway in the anticonvulsant effect of CBD
GPR55 Receptor: CBD possesses affinity for multiple targets, including the orphan G protein-coupled receptor-55 (GPR55)
Adenosine System: Enhancing endogenous adenosine levels in the CNS thereby increasing inhibitory adenosinergic tone which aids in seizure suppression
Calcium Regulation: Regulation of Ca2+ homeostasis in neurons under a normal or a highly excitable state

Additional Mechanisms

5-HT1A Receptors: Agonistic properties at 5-HT1A receptors eliciting membrane hyperpolarising responses
Neuroprotective Effects: CBD has been shown to reduce inflammation, protect against neuronal loss, normalize neurogenesis, and act as an antioxidant

Clinical Evidence: 2021-2025 Research Updates

Pivotal Clinical Trials

A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies' approval was granted based on four pivotal double-blind, placebo-controlled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones.

Dravet Syndrome Results

The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points.

Lennox-Gastaut Syndrome Results

In another study, there was a 44% monthly reduction in drop seizures among patients taking EPIDIOLEX in the 20 mg/kg/day group, compared with a 22% reduction taking placebo. 4% of people taking EPIDIOLEX 20 mg/kg/day (compared with 0% of people taking placebo) reported no drop seizures.

Tuberous Sclerosis Complex Results

Epidiolex's effectiveness for the treatment of seizures associated with TSC was established in a randomized, double-blind, placebo-controlled trial where 148 patients out of a total of 224 in the study received Epidiolex. In the study, patients treated with Epidiolex had a significantly greater reduction in the frequency of seizures during the treatment period than patients who received placebo.

Long-Term Safety and Efficacy Data

New Evidence (2021-2024): Several major studies have now provided long-term data on CBD's safety and efficacy:

Four-Year Follow-Up Data

Add-on CBD was associated with sustained seizure reduction up to 192 weeks with an acceptable safety profile and can be used for long-term treatment of TREs. This represents the longest follow-up data available for pharmaceutical CBD in epilepsy treatment.

Pediatric Long-Term Safety

Treatment was well tolerated in doses up to 50 mg/kg/day. Patients who did not achieve desired results at a dose of ≤25.0 mg/kg/day reported more AEs when CBD dose increased to >25.0 mg/kg/day.

Real-World Evidence

A retrospective analysis of medical records of 139 children and young adults (54.7% female, median age 12.0 years) with DRE treated with purified CBD from 2018 to 2022 at five medical centers in Israel. Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had >50% reduction.

Focal Seizures: New Evidence

The use of cannabidiol (CBD) was associated with reductions in focal-onset seizure, including focal aware seizures (FAS), focal impaired awareness seizures (FIAS), and focal to bilateral tonic-clonic seizures (FBTCS), with an acceptable safety profile. This expands CBD's potential beyond the originally approved rare childhood epilepsies.

Safety Profile and Side Effects

The most common adverse effects (AEs) are drowsiness, reduced appetite, diarrhea, and vomiting. Transaminase elevation is the most common AE that leads to CBD discontinuation.

Common Side Effects

Drowsiness/Somnolence (25% of patients)
Decreased appetite (19%)
Diarrhea (19%)
Fatigue (13%)
Elevated liver enzymes
Fever and vomiting

Serious Safety Considerations

Epidiolex may cause liver problems. Your doctor may order blood tests to check your liver before and during EPIDIOLEX treatment. In some cases, EPIDIOLEX treatment may need to be stopped.

Coadministration with valproate may increase the risk of hepatotoxicity. The combination of CBD and clobazam may increase both the effectiveness and the risk of AEs associated with these drugs.

Long-Term Safety

Compelling evidence supports the efficacy of CBD in experimental models and patients with epilepsy. In randomized clinical trials, highly-purified CBD has demonstrated efficacy with an acceptable safety profile in children and adults with difficult-to-treat seizures.

Drug Interactions and Clinical Considerations

CBD can interact with other medications, particularly:

Valproate: Increased risk of liver problems
Clobazam: Enhanced effects and side effects of both drugs
Other AEDs: Various interactions affecting drug levels

Future Directions: Upcoming Trials and Research

2025 Clinical Trials

Two national NHS clinical trials will investigate the safety and effectiveness of cannabidiol (CBD) and tetrahydrocannabinol (THC) in adults and children with treatment-resistant epilepsy. The trials will randomly assign CBD, CBD with a small amount of THC or placebo to a total of 500 adults and children with medicine-resistant (refractory) early-onset and genetic generalised epilepsies for 24 weeks.

These will be the world's first double blind randomised controlled trials to investigate the use of CBD and THC together for epilepsy, and the first to evaluate the medicines in children and adults who have a broad range of difficult-to-treat epilepsies.

Research Gaps

The most striking gaps in knowledge are the efficacy and optimal dose of CBD for adults with focal epilepsies, the long-term safety of CBD use, and strategies to improve access to CBD for people living with epilepsy.

CBD as Complementary Treatment

Research suggests CBD works best as an add-on therapy to existing anti-epileptic drugs rather than a standalone treatment. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy.

CBD may also help reduce side effects of traditional AEDs by:

Stabilizing mood and reducing irritability
Alleviating nausea and stomach discomfort
Providing neuroprotective benefits

Access and Regulatory Status

EPIDIOLEX/EPIDYOLEX net product sales rose by 15% to USD 972.4 million in 2024, indicating growing acceptance and use of pharmaceutical CBD for epilepsy treatment.

Currently, Epidiolex/Epidyolex is the only FDA and EMA-approved CBD medication for epilepsy. Hemp oil is federally legal and contains less than or equal to 0.3% THC and is hemp derived. It can be bought over the counter at pharmacies, grocery stores, and even gas stations. Although it is becoming increasingly common to see patients on hemp oil because of the ease of access, it is important to recognize that none of these products are FDA approved and have efficacy data in relation to seizures.

Bottom Line: Perspectives

The evidence for CBD in epilepsy treatment has significantly strengthened since 2020. During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published.

Overall, adjunct CBD has been found to be generally safe and effective for treatment-resistant seizures in children with severe early-onset epilepsy. Long-term data now supports sustained efficacy for up to four years with an acceptable safety profile.

Key takeaways for 2025:

Proven efficacy: CBD is established as effective for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex
Long-term safety: Four-year data confirms acceptable safety profile
Expanding indications: Emerging evidence for focal seizures and other epilepsy types
Combination therapy: Works best as add-on to existing treatments
Ongoing research: Major trials in 2025 will explore CBD+THC combinations

Important: Always consult with a qualified neurologist or epilepsy specialist before considering CBD treatment. Pharmaceutical-grade CBD (Epidiolex/Epidyolex) should be used under medical supervision, as it can interact with other medications and requires careful monitoring.

References

Studies and sources used in this article include:

IN COOPERATION WITH MYDOSAGE

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