CBD for Epilepsy

How does CBD affect epileptic seizures?

Cannabidiol (CBD) acts antiepileptically by modulating multiple neuronal and inflammatory signaling pathways – including influencing calcium channels, adenosine pathways, GABAergic transmission, and inhibiting excitatory glutamate receptors. CBD does not act directly on classical cannabinoid receptors (CB1/CB2) but exerts its effect through a broader molecular network.

CBD acts on epileptic seizures not via CB1/CB2 like THC, but through a multimodal effect on ion channels, neurotransmitters, and inflammatory pathways. This makes it an innovative addition, especially in the form of the approved medicinal product, particularly for therapy-resistant epilepsy Epidiolex®, whose effect is based on a broad molecular target structure supports.

 Which types of epilepsy can be treated with CBD?

Cannabidiol (CBD), especially in the form of the approved medicinal product Epidiolex®, primarily used for the treatment of rarer, therapy-resistant forms of epilepsy used. The best scientific evidence exists for Dravet syndrome, which Lennox-Gastaut syndrome as well as the Tuberous sclerosis complex. In addition, there is evidence of efficacy in other difficult-to-treat epilepsies, including in adulthood.

CBD is currently officially approved for three difficult-to-treat forms of epilepsy: Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. The evidence is based on large-scale, randomized phase III studies with Epidiolex®. For other forms of epilepsy such as West syndrome or focal epilepsies, there is only observational or experimental evidence before – here the use must be assessed individually and off-label.

What does science say about the effect of CBD on epilepsy?

The scientific evidence for the effect of cannabidiol (CBD) on epilepsy is particularly well established for certain treatment-resistant syndromes such as Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. Several large, randomized, placebo-controlled studies have shown that CBD – mostly in the form of the drug Epidiolex® – can significantly reduce seizure frequency. The effect is not based on classical cannabinoid receptors but on a multimodal mechanism of action: CBD influences, among others, TRPV1, GPR55, and 5-HT1A receptors, inhibits proinflammatory signaling pathways (e.g., via NF-κB), and enhances the anticonvulsant properties of endogenous messengers like anandamide. Clinical research shows good tolerability and a low rate of serious side effects, especially compared to other antiepileptic drugs. Nevertheless, CBD is not equally effective for all forms of epilepsy, and outside the approved indications, it is an off-label use whose benefit must be assessed individually.

 Is CBD an alternative to antiepileptic drugs or an add-on?

According to the current state of science, CBD should primarily be considered an add-on therapy – not a complete replacement for classic antiepileptic drugs.

In the major approval studies for Epidiolex® (pure CBD) cannabidiol was used exclusively as a concomitant measure is used in addition to existing antiepileptic medication – typically in patients with therapy-resistant epilepsythat responded inadequately to several other medications. It was shown that CBD frequency and severity of epileptic seizures can significantly reduce, especially in Dravet and Lennox-Gastaut syndromes. The therapeutic effect was dose-dependent, but never sufficient alone to achieve complete seizure freedom.

Scientific reviews (e.g., Silvestro et al., 2019) and clinical guidelines emphasize that CBD is currently not recommended as monotherapy is used, but exclusively as a additive therapy option in difficult-to-treat cases. So far, there are no randomized studies, in which classic antiepileptic drugs were completely replaced by CBD.

However, CBD can in individual cases enable a reduction of concomitant medication allow – e.g., by lowering the dose of clobazam, which can reduce side effects. This requires medical supervision, as CBD affects CYP450 enzymes alters the plasma levels of many antiepileptic drugs.

Conclusion: CBD is not an alternative in the sense of a complete replacement of antiepileptic drugs, but rather a meaningful add-on, especially in therapy-resistant childhood epilepsy forms. A complete replacement should only be done within clinical trials or individual off-label attempts under strict medical supervision.

How safe is the use of CBD in children with epilepsy?

The use of cannabidiol (CBD) in children with epilepsy is considered well tolerated and safe according to current studies – especially within the approved indication with Epidiolex®. In several large randomized controlled trials (e.g., Devinsky et al., 2017; Thiele et al., 2018), the safety of oral CBD in doses between 10 and 20 mg/kg body weight per day in children with Dravet or Lennox-Gastaut syndrome were extensively studied. The most common side effects were drowsiness, diarrhea, decreased appetite, and elevated liver enzymes (ALT/AST) — the latter especially with simultaneous intake of Valproic acid.

was observed in approval studies no relevant impairment of cognitive or neurological development has been observed with CBD. On the contrary, parents often report improved alertness, social interaction, and quality of life, even with incomplete seizure control.

Despite this positive record, the use of CBD in children should only under medical supervision occur — especially due to possible interactions with other antiepileptic drugs (e.g., clobazam, topiramate) and the need for regular liver function monitoring. Long-term data over many years are still limited, which is why a careful benefit-risk assessment is indicated.

CBD is well studied, largely safe, and well tolerated in children with difficult-to-treat epilepsy (especially Dravet, LGS, TSC) — provided it is used under controlled medical supervision. Outside these indications, use is off-label and requires particularly strict medical oversight.

Which CBD preparations are approved for epilepsy?

Epidiolex® is the only cannabidiol (CBD)-containing medicine approved in the USA and Europe for the treatment of certain forms of epilepsy. In the USA, Epidiolex® was approved in 2018 for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients from two years of age. In 2020, the approval was extended to seizures associated with tuberous sclerosis complex. In Europe, the preparation is marketed under the name Epidyolex® known and used in combination with clobazam to treat seizures in Lennox-Gastaut syndrome and Dravet syndrome in patients from two years of age.

Regarding the magistral preparation of CBD (CBD-API) for the treatment of epilepsy, there is currently no specific information about approved preparations. Magistral preparations are individually made medications in the pharmacy, produced on medical prescription for a specific patient. The use of CBD in such preparations usually occurs outside approved indications (off-label use) and should only be done under strict medical supervision.

Are there differences between isolated CBD and full-spectrum CBD?

Isolated cannabidiol is a highly pure active ingredient (>99%), the no other cannabinoids, terpenes, or flavonoids contains. It is usually produced in pharmaceutical quality (e.g., as an active ingredient in Epidiolex®) and allows a precise dosing without THC content.

• Advantages: High reproducibility, no THC risk (also relevant for drug tests), ideal for THC sensitivity or in children.

• Limitations: In studies, isolated CBD sometimes showed a weaker or less robust effect as cannabinoid-rich extracts – especially at very low doses. It often shows a U-shaped dose-response curve.

Full-spectrum preparations contain, besides CBD, also other naturally occurring cannabinoids (e.g., CBG, CBC, traces of THC), Terpenes and other plant substances. This combination is often referred to as “Entourage effect” discussed – the synergistic effect of several active substances that work stronger or more stable together than isolated.

• Advantages: Possibly stronger overall effect due to synergy, especially in chronic pain, inflammation, or anxiety disorders.

• Limitations: THC content (also <0.2%) can cause unwanted effects (e.g., sedation, interactions), legally and toxicologically not always clear, harder to standardize.

The clinical evidence for anticonvulsant effect of CBD comes almost exclusively from studies with pure, isolated CBD (Epidiolex®). For full-spectrum CBD, there are hardly any controlled studies in epilepsy, so here only indirect statements are possible. In epilepsy – especially in childhood – isolated CBD preferred to to avoid interactions and THC effects.

What experiences exist with CBD in treatment-resistant epilepsy?

The experience with CBD in treatment-resistant epilepsy is overall positive – both from scientific studies and clinical case reports and patient observations. Especially in children with rare, difficult-to-treat forms of epilepsy such as Dravet syndrome, the Lennox-Gastaut syndrome (LGS) and the Tuberous sclerosis complex (TSC) cannabidiol was able to significantly reduce seizure frequency – often despite previous failure of several classic antiepileptics.

How is CBD properly dosed for epilepsy?

The dosage of cannabidiol (CBD) for epilepsy depends on body weight, type of epilepsy, and individual tolerance. Clinical studies and approval recommendations usually start with 2.5 mg/kg body weight twice daily (a total of 5 mg/kg/day) started. If well tolerated, the dose can be gradually increased to max 10 mg/kg twice daily (20 mg/kg/day) can be increased. This guideline applies especially to the approved preparation Epidiolex® (Epidyolex in Europe).

Higher doses (>20 mg/kg/day) have been used in studies but are not officially approved and are associated with a higher risk of side effects.

 What side effects can occur with CBD therapy?

Cannabidiol (CBD) is generally considered well tolerated, especially compared to classic antiepileptics. Nevertheless, at therapeutically effective doses – especially from 10–20 mg/kg/day – it can cause mild to moderate side effects are affected. These usually occur dose-dependently and mainly affect the gastrointestinal tract, which central nervous system as well as the Liver function.

CBD is well tolerated in epilepsy, but not free of side effects. The most common effects are mild to moderate, however, require regular monitoring, especially in combination with other antiepileptics such as Valproic acid or ClobazamA structured therapy initiation under medical supervision is therefore essential.

Literature & Sources

• Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., ... Wright, S. (2017). Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. New England Journal of Medicine, 376(21), 2011–2020. DOI: 10.1056/NEJMoa1611618
• Devinsky, O., Patel, A. D., Cross, J. H., Villanueva, V., Wirrell, E. C., Privitera, M., ... Thiele, E. A. (2018). Effect of cannabidiol on drop seizures in the Lennox–Gastaut syndrome. New England Journal of Medicine, 378(20), 1888–1897. DOI: 10.1056/NEJMoa1714631
• Gaston, T. E., et al. (2023). Cannabidiol as an add-on treatment in patients with refractory epilepsy: Recent evidence and clinical experience. Epilepsy & Behavior. DOI: 10.1016/j.yebeh.2023.109097
• Devinsky, O., et al. (2024). Cannabidiol in adults with treatment-resistant epilepsy: Preliminary results. Journal of Neurology, Neurosurgery & Psychiatry, 95(Suppl 2), A30.2. DOI: 10.1136/jnnp-2023-BNA.75
• Szaflarski, J. P., et al. (2022). Cannabidiol improves seizure frequency and quality of life in treatment-resistant epilepsy: Real-world evidence. JAMA Network Open, 5(7), e2220165. DOI: 10.1001/jamanetworkopen.2022.20165
• Perucca, E. (2017). Cannabidiol as a new treatment for epilepsy in adults and children. Epilepsia, 59(5), 792–801. PMC: PMC6514832
• Devinsky, O., et al. (2017). Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Epilepsia, 58(8), 1407–1417. DOI: 10.1111/epi.13852
• Thiele, E. A., et al. (2022). Long-term safety and efficacy of cannabidiol in patients with Lennox–Gastaut syndrome: Expanded access program results. Epilepsia, 63(5), 1110–1123. DOI: 10.1111/epi.17150
• Nichols, J. M., & Kaplan, B. L. F. (2016). Immune responses regulated by cannabidiol. Cannabis and Cannabinoid Research, 1(1), 59–67. DOI: 10.1089/can.2016.0034
• Ärzte Exklusiv. (2019). Cannabidiol: Medical applications and research status. Retrieved from ärzte-exklusiv.at
• European Medicines Agency (EMA). (2019). Epidyolex: EPAR – Summary for the public. Retrieved from ema.europa.eu
• U.S. Food & Drug Administration (FDA). (2023). FDA regulation of cannabis and cannabis-derived products including cannabidiol (CBD). Retrieved from fda.gov
• Hložek, T., et al. (2022). Pharmacokinetics and behavioral effects of cannabidiol in preclinical models. Frontiers in Physiology, 13, 1044575. DOI: 10.3389/fphys.2022.1044575
• Thiele, E. A., et al. (2018). Cannabidiol in patients with seizures associated with Lennox–Gastaut syndrome (GWPCARE4): a randomized, double-blind, placebo-controlled phase 3 trial. The Lancet, 391(10125), 1085–1096. DOI: 10.1016/S0140-6736(18)30136-3