23/06/2020
Cannabidiol: A New Frontier in Epilepsy Treatment
Epilepsy, a neurological disorder characterised by recurrent, unprovoked seizures, affects millions worldwide. For a significant portion of these individuals, conventional antiepileptic drugs (AEDs) prove insufficient, leading to the challenging condition of drug-resistant epilepsy (DRE). In recent years, a molecule derived from the cannabis plant, cannabidiol (CBD), has emerged as a promising therapeutic avenue. Unlike its well-known counterpart, tetrahydrocannabinol (THC), CBD is non-psychoactive and has demonstrated a consistent efficacy in managing certain severe forms of epilepsy, particularly in childhood-onset syndromes.
Understanding Cannabidiol (CBD)
Cannabidiol is one of over 100 cannabinoids identified in the Cannabis sativa plant. It is a non-intoxicating compound, meaning it does not produce the 'high' associated with cannabis use. Its therapeutic potential extends beyond epilepsy, with research exploring its use in various neurological and psychiatric conditions. CBD can be synthesised or extracted from the cannabis plant, leading to different product formulations, including highly purified pharmaceutical-grade CBD. It's crucial to distinguish between these pharmaceutical-grade products and the wide array of over-the-counter CBD supplements, which may vary significantly in purity, concentration, and regulatory oversight.
CBD for Epilepsy: The Evidence Base
The journey of CBD as an epilepsy treatment gained significant momentum following compelling anecdotal reports and early clinical observations. Landmark studies have focused on specific, severe, and treatment-resistant epileptic encephalopathies, most notably Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). These conditions are characterised by frequent, debilitating seizures that are notoriously difficult to control with standard medications.
Randomised, double-blind, placebo-controlled trials have been instrumental in establishing the efficacy of pharmaceutical-grade CBD. These studies, often involving children and adolescents, have consistently shown a significant reduction in seizure frequency compared to placebo. For instance, trials investigating CBD as an add-on therapy for DS and LGS reported median reductions in convulsive or drop seizures ranging from 30% to over 40% in the CBD groups. Responder rates, defined as a 50% or greater reduction in seizures, were also significantly higher in patients receiving CBD.
Furthermore, research has extended to other rare epilepsy syndromes, such as tuberous sclerosis complex (TSC), with similar positive outcomes observed. While the primary focus has been on severe childhood-onset epilepsies, research is ongoing to explore CBD's effectiveness in other forms of epilepsy, including adult-onset and focal epilepsies.
Approved Treatments and Regulatory Landscape
The robust clinical evidence has led to regulatory approval of CBD-based medications in several jurisdictions. In the UK, for example, Epidyolex, a highly purified liquid containing CBD, is the first and only cannabis-based medicine approved for treating certain types of epilepsy. NICE (National Institute for Health and Care Excellence) recommends Epidyolex as an add-on treatment for individuals, aged two and above, diagnosed with Dravet syndrome or Lennox-Gastaut syndrome, provided they have already tried at least two other epilepsy medications without sufficient seizure control.
The regulatory landscape for cannabis-based medicines has evolved significantly. In the UK, a rescheduling of cannabis-based medicines in 2018 enabled specialist doctors to prescribe them for patients with severe and treatment-resistant epilepsies. However, it's important to note that NICE guidelines have not made practice recommendations for all severe and treatment-resistant epilepsies, highlighting the need for further research, particularly into cannabis-based medicines containing THC.
Mechanism of Action and Cognitive/Behavioural Effects
The precise mechanism by which CBD exerts its anticonvulsant effects is still under investigation. However, current research suggests it may involve modulation of intracellular calcium mobilisation through pathways like GPR55 and TRPV1, as well as influencing adenosine-mediated signalling. Unlike THC, CBD does not directly bind to CB1 or CB2 receptors.
Beyond seizure control, emerging evidence suggests CBD may have positive effects on behaviour and cognition. Several studies have reported an improved overall condition and behavioural changes in patients receiving CBD, although formal neurocognitive assessments are still limited. Animal studies indicate that CBD may positively influence social behaviour, reduce hyperactivity, and improve cognitive functions such as working memory. This potential psychotropic impact, particularly on frontal lobe-mediated behaviours, warrants further rigorous investigation in human trials.
Potential Side Effects and Drug Interactions
While CBD is generally considered well-tolerated, its use is associated with potential side effects. The most commonly reported adverse events (AEs) in clinical trials include somnolence, decreased appetite, diarrhoea, and fatigue. A more significant concern is the potential for elevated liver enzymes (transaminases), which in some cases has led to the discontinuation of treatment. This risk appears to be higher in patients also taking valproate, necessitating careful liver function monitoring.
Drug-drug interactions are also a critical consideration, particularly given that patients with DRE are often on multiple AEDs. CBD can inhibit certain cytochrome P450 (CYP) enzymes, potentially affecting the metabolism of other medications. The interaction with clobazam (CLB) is particularly noteworthy. While the combination may enhance seizure control, it can also lead to increased levels of clobazam's active metabolite, N-methylclobazam, potentially exacerbating side effects like sedation. Careful monitoring and dose adjustments of concomitant medications are essential.
Challenges and Future Directions
Despite the promising therapeutic potential, several challenges remain in the widespread use of CBD for epilepsy:
- Cost: Pharmaceutical-grade CBD treatments can be expensive, posing a barrier to access for some patients.
- Availability: Access to prescribed CBD may be limited outside of specific clinical trial settings or regulatory approvals.
- Product Variability: The market is flooded with non-pharmaceutical CBD products of questionable quality and purity, which should not be confused with approved medical treatments.
- Further Research: More research is needed to fully understand CBD's efficacy in various epilepsy types, its long-term safety profile, optimal dosing strategies, and its potential benefits for cognitive and behavioural aspects of epilepsy.
Key Takeaways
Cannabidiol represents a significant advancement in the treatment of specific, severe forms of drug-resistant epilepsy, particularly Dravet and Lennox-Gastaut syndromes. Its non-psychoactive nature and demonstrated efficacy in reducing seizure frequency make it a valuable addition to the therapeutic arsenal. However, responsible use necessitates understanding its approved indications, potential side effects, crucial drug interactions, and the importance of using only pharmaceutical-grade, regulated products. Ongoing research promises to further elucidate CBD's role and expand its potential applications in epilepsy management.
Frequently Asked Questions (FAQs)
- Q1: Is CBD a cure for epilepsy?
- No, CBD is not a cure for epilepsy. It is a treatment option that can help reduce the frequency and severity of seizures in certain types of epilepsy, particularly Dravet syndrome and Lennox-Gastaut syndrome, when used as an add-on therapy.
- Q2: Can I buy CBD over the counter for epilepsy?
- While CBD products are widely available over the counter, these are not regulated as medicines and their quality, purity, and concentration can vary significantly. For epilepsy treatment, a doctor-prescribed, pharmaceutical-grade CBD product like Epidyolex is recommended and regulated.
- Q3: What are the most common side effects of CBD for epilepsy?
- The most common side effects include drowsiness, reduced appetite, diarrhoea, and fatigue. Elevated liver enzymes are also a noted concern, particularly when used with valproate.
- Q4: Does CBD interact with other epilepsy medications?
- Yes, CBD can interact with other medications, most notably clobazam, potentially increasing its levels and associated side effects. It's crucial to inform your specialist about all medications you are taking.
- Q5: Is CBD effective for all types of epilepsy?
- Currently, the strongest evidence for CBD's effectiveness is in specific severe childhood-onset epilepsies like Dravet syndrome and Lennox-Gastaut syndrome. Research is ongoing to determine its efficacy in other epilepsy types.
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