What is the role of cannabidiol (CBD) in treating seizures, particularly in patients with Dravet syndrome or Lennox-Gastaut syndrome?

Cannabidiol (CBD) for Seizure Management in Dravet and Lennox-Gastaut Syndromes

Cannabidiol (CBD) is highly effective as an adjunctive treatment for reducing seizure frequency in patients with Dravet syndrome and Lennox-Gastaut syndrome, with FDA-approved formulations showing 30-48% greater seizure reduction compared to placebo. 1, 2, 3

Evidence-Based Efficacy

The FDA has approved Epidiolex, a purified CBD formulation, for the treatment of seizures associated with:

• Lennox-Gastaut syndrome
• Dravet syndrome
• Tuberous sclerosis complex 1

Clinical trials demonstrate significant benefits:

• Dravet Syndrome:

  • 10 mg/kg/day CBD reduced convulsive seizures by 48.7% vs 26.9% with placebo
  • 20 mg/kg/day CBD reduced convulsive seizures by 45.7% vs 26.9% with placebo 2

• Lennox-Gastaut Syndrome:

  • 10 mg/kg/day CBD reduced drop seizures by 37.2% vs 17.2% with placebo
  • 20 mg/kg/day CBD reduced drop seizures by 41.9% vs 17.2% with placebo 4

• Long-term benefits: Sustained seizure reduction of 45-74% for convulsive seizures and 49-84% for total seizures over 156 weeks of treatment 5

Dosing Recommendations

• Starting dose: 2.5 mg/kg twice daily (5 mg/kg/day)
• Maintenance dose: 10 mg/kg/day (divided into two doses)
• Maximum dose: Can be increased to 20 mg/kg/day based on clinical response and tolerability 2, 4

The 10 mg/kg/day dose offers similar efficacy to higher doses with better tolerability and fewer adverse effects 2.

Safety Profile and Adverse Effects

Common adverse effects include:

• Somnolence (28%)
• Decreased appetite (31%)
• Diarrhea (43%)
• Fatigue
• Pyrexia (39%) 5

Important safety considerations:

1. Liver function: Elevated liver transaminases occur in approximately 9-14% of patients, particularly when co-administered with valproate 2, 4

   • Monitor liver function tests before treatment and at 1,3, and 6 months, then periodically
   • 84% of cases with elevated transaminases were on concomitant valproic acid 5

2. Drug interactions: CBD may interact with other antiseizure medications through inhibition of cytochrome P450 enzymes 1

3. Discontinuation rate: Approximately 9% of patients discontinue due to adverse events in long-term treatment 5

Advantages Over Other Cannabinoids

CBD is distinct from other cannabinoids like THC (tetrahydrocannabinol):

• No psychoactive effects
• No high potential for misuse
• Does not cause respiratory depression even with excessive dosing 1

Clinical Implementation

For patients with treatment-resistant Dravet or Lennox-Gastaut syndrome:

1. Confirm diagnosis and ensure seizures are not controlled with conventional antiseizure medications
2. Start with 2.5 mg/kg twice daily for one week
3. Titrate to 5 mg/kg twice daily (10 mg/kg/day) over 2 weeks
4. Monitor response for 4-8 weeks before considering dose increase
5. Consider increasing to 20 mg/kg/day only if seizure control is inadequate and no significant adverse effects occur
6. Regular monitoring:
   • Liver function tests (especially with concomitant valproate)
   • Seizure frequency
   • Adverse effects
   • Quality of life measures

Limitations and Considerations

• CBD is not approved for other forms of epilepsy outside Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex
• Medical cannabis products that are not FDA-approved have inconsistent quality, potency, and safety profiles
• Patients should be educated about the difference between FDA-approved CBD (Epidiolex) and non-regulated cannabis products 1

CBD represents a significant advancement in the treatment of these rare, severe epilepsy syndromes that often resist conventional treatments, offering hope for improved seizure control and quality of life.