Cannabidiol (CBD) in epilepsy: Uses and research on it

On World Epilepsy Day, we bring you a post about the role of CBD in the treatment of this disease and the research about it. We remind you that this is an informative article that is not intended to prevent, diagnose or treat any disease. Consult with your physician before using CBD. Cannactiva products are not medicines.

Between 12,000 and 22,000 new cases of epilepsy are diagnosed each year in Spain. It is estimated that in our country there are around 400,000 patients with epilepsy, which makes this disorder one of the most frequent neurological problems in our society.

Introduction to epilepsy and research with cannabinoids

What is epilepsy?

Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. Seizures are episodes of abnormal brain activity that may manifest themselves in different ways, such as involuntary movements, sensory disturbances or changes in the level of consciousness.

Epilepsy can have different causes, such as genetic disorders, brain injuries, infectious diseases or brain tumors. Although epilepsy can affect people of any age, it is most common in childhood and early adulthood.

Treatment of epilepsy usually involves antiepileptic drugs, but in some cases surgery may also be necessary to remove the focus of abnormal activity in the brain. In many cases, epilepsy can be successfully controlled and people with this condition can lead normal lives.

How does CBD act on the mechanisms of epilepsy?

Epilepsy consists of a pathological hyperstimulation of a specific group of neurons in the brain. The CBD or cannabidiol appears to act through several different mechanisms to reduce seizure activity. It may increase the activity of inhibitory or “depressant” neurotransmitter systems in the central nervous system (CNS), such as gamma-aminobutyric acid(GABA), and reduce the activity of excitatory or activating neurotransmitter systems, such as serotonin. The anti-inflammatory properties of CBD may exert effects on oxidation in the brain, which would contribute to neuronal protection (neuroprotection) and reduction of seizure activity.

Is CBD the only cannabinoid useful in the treatment of epilepsy?

CBD is the most studied cannabinoid in the context of epilepsy treatment having shown some beneficial effects in reducing seizure frequency in some studies.

The THC (tetrahydrocannabinol) is another cannabinoid present in cannabis that has been studied in the context of epilepsy treatment. THC is widely known to be the psychoactive component of marijuana and its regulation as an illegal drug.

However, the results of studies on THC and epilepsy are more controversial and it is less clear whether THC has a beneficial effect in reducing seizure frequency. Some studies have suggested that THC may have positive effects on epilepsy, others have found no significant effect, and still others have found that THC may promote seizures in some types of patients or epilepsies.

Uses of CBD in the treatment of epilepsy

What are the potential benefits of CBD over other conventional antiepileptic drugs?

Cannabidiol may have some advantages over other drugs in the conventional antiepileptic family. CBD has been shown to control seizures well in some types of epilepsy that are resistant to all other medications used.

On the other hand, conventional antiepileptic drugs are often effective, but have significant side effects: memory problems, behavioral changes, changes in appetite and weight, excessive drowsiness, motor coordination problems… In this sense, cannabidiol offers the advantage of a profile of much more tolerable adverse effects for the patient.

In what type of epilepsies is CBD authorized for use as an antiepileptic?

In 2018, the FDA (U.S. Food and Drug Administration) approved the use of cannabidiol as a treatment for two severe forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, in children over 2 years of age (Epidiolex ®). This was the first time CBD was approved as a medical treatment in the United States. In Europe, the drug was approved for these same indications in April 2021. In Spain there is also a Clinical Guide for its use (1).

Dravet syndrome and Lennox-Gastaut syndrome are two severe types of epilepsy characterized by the presence of seizures and neurodevelopmental delay and intellectual disability. Both conditions occur more frequently in children and may be caused by genetic disorders or brain injury. Cannabidiol reduces the number of seizures in children with these diseases by 30-70%, which is a very significant advance (2).

Is CBD being studied in any other type of epilepsy?

The good results obtained in the aforementioned syndromes have led to the start of new studies in which CBD is added to conventional treatment in other severe epileptic syndromes that are difficult to control. In general, these are very rare (but very severe) epilepsies such as tuberous sclerosis, Aicardi syndrome, Ohtahara syndrome, Jeavons syndrome, Doose syndrome, epilepsies of genetic origin (CDKL5 mutation, dup 15 d mutations…) or neuronal ceroid lipofuscinosis (3).

The results indicate that cannabidiol could reduce seizure frequency and may have an adequate safety profile in children and young adults with highly refractory epilepsy. But well-designed clinical trials in each of these diseases are needed to characterize the safety profile and true efficacy of this compound.

How CBD is used for epilepsy

How much CBD is administered in the treatment of epilepsy?

The administration of CBD in cases of childhood epilepsy should be monitored in a personalized way and with the prescription and follow-up of a medical specialist. Drug administration in children is done more strictly than in adults, considering the patient’s weight.

Based on current clinical guidelines, the starting dose of cannabidiol for epilepsy is 5 mg CBD/kg per day, divided into two doses (2.5 mg/kg/12 hours) during the first week, which is doubled the following week (10 mg/kg/day in two doses of 5 mg/kg/12 hours). Most patients are usually controlled at this dose, which can be progressively raised to a recommended maximum of 20 mg CBD/kg/day (4).

By what route is CBD used in epilepsy?

The approved pharmaceutical product is Epidiolex®, a purified and standardized cannabis plant extract with a high cannabidiol content. It is administered as an oral solution.

Can CBD be used in combination with other antiepileptic drugs?

CBD influences the metabolism (the rate at which the body breaks down other drugs) of two commonly used antiepileptic drugs: clobazam and sodium valproate (5). It also presents possible interactions with other drugs. The use of cannabidiol in patients who are using either of these two drugs should be specially monitored by a specialist.

Are there data on the use of CBD as an antiepileptic in adults?

Although there are no well-designed clinical trials with available results, we do have surveys of adult patients using CBD as a treatment for epilepsy in which doses of 50 mg per day appear to control some types of epilepsy (6). Another study in which up to 200 mg of cannabidiol has been administered daily in patients with epilepsies resistant to other treatments has also shown positive results (7).

We remind you that this is an informative article that is not intended to prevent, diagnose or treat any disease. Consult your doctor before using CBD. Its content can complement, but never replace, the diagnosis or treatment of any disease or symptom. Cannactiva products are not medicines.

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Referencias
  1. García-Peñas JJ, Gil-Nagel A, Sánchez-Carpintero R, Villanueva V. Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: expert recommendations on its use in clinical practice in Spain. Rev Neurol 2021;73 (Suppl. 1):S1-S8. DOI: 10.33588/rn.73S01.2021250
  2. Talwar A, Estes E, Aparasu R, Reddy DS. Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis, Experimental Neurology, Volume 359, 2023, 114238, ISSN 0014-4886. DOI: https://doi.org/10.1016/j.expneurol.2022.114238.
  3. Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24. Erratum in: Lancet Neurol. 2016 Apr;15(4):352. PMID: 26724101.
  4. European Medicines Agency (EMA) Science Medicines Health. Epidyolex (cannabidiol). Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex
  5. Patsalos PN, Szaflarski JP, Gidal B, VanLandingham K, Critchley D, Morrison G. Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Epilepsy. 2020 Sep;61(9):1854-1868. doi: 10.1111/epi.16674. Epub 2020 Sep 12. PMID: 32918835; PMCID: PMC7693203.
  6. Strickland JC, Jackson H, Schlienz NJ, Salpekar JA, Martin EL, Munson J, Bonn-Miller MO, Vandrey R. Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy. Epilepsy Behav. 2021 Sep;122:108205. doi: 10.1016/j.yebeh.2021.108205. Epub 2021 Jul 27. PMID: 34311183.
  7. Morano A, Fanella M, Albini M, Cifelli P, Palma E, Giallonardo AT, Di Bonaventura C. Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects. Neuropsychiatr Dis Treat. 2020 Feb 7;16:381-396. doi: 10.2147/NDT.S203782. PMID: 32103958; PMCID: PMC7012327.
  8. Silvestro S, Mammana S, Cavalli E, Bramanti P, Mazzon E. Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Safety in Clinical Trials. Molecules. 2019 Apr 12;24(8):1459. doi: 10.3390/molecules24081459. PMID: 31013866; PMCID: PMC6514832.

Dr. Fernando Caudevilla
Family Physician | Expert in Drug Addictions. He works in different assistance, research and training projects related to drugs, including therapeutic cannabis.

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