CBD Anticonvulsant Sim

Hyperexcitable Neural Network

Dravet and Lennox-Gastaut syndromes resist standard anti-epileptic drugs.

• Infancy: Dravet syndrome onset (first year of life)
• ≥2: AEDs tried before failure (refractory definition)
• 24: Seizures per month (baseline) (typical trial cohort)
• Poor: Standard AED response (drug-resistant seizures)

Refractory syndromes

Dravet and LGS cause frequent, drug-resistant seizures from early childhood.

Both syndromes are defined by failure of multiple standard anti-epileptics.

Hyperexcitable circuits

Cortical neurons fire in abnormal, synchronized bursts that spread as seizures.

Unmet need

New mechanisms beyond sodium/GABA-targeting AEDs are needed for these patients.

Purified CBD (Epidiolex) Dosed

FDA-approved oral CBD solution added on top of existing therapy.

• 2018: Approval (FDA, Epidiolex)
• 20 mg/kg/day: Target dose (typical maintenance)
• Oral solution: Route (purified plant-derived CBD)
• <0.1%: THC content (non-intoxicating)

Add-on therapy

CBD is added to existing anti-epileptic regimens, not used alone.

Epidiolex is purified CBD, distinct from whole-plant cannabis extracts.

Dose titration

Dosing is gradually increased over weeks toward a target maintenance level.

CNS penetration

CBD crosses the blood-brain barrier and reaches cortical neurons.

GPR55 and TRPV1 Modulation

CBD acts on multiple non-CB1 targets, unlike THC.

• Antagonist: GPR55 (reduces excitatory signaling)
• Desensitizer: TRPV1 (channel activity lowered)
• Minimal: CB1 activity (non-psychoactive profile)
• Multiple: Proposed targets (polypharmacology)

GPR55 signaling

GPR55 normally increases neuronal excitability; CBD antagonizes this receptor.

Lowering GPR55 tone reduces excitatory drive on hyperexcitable circuits.

TRPV1 channels

Sustained CBD exposure desensitizes TRPV1, dampening calcium-driven excitability.

Not THC-like

CBD has negligible CB1 activity, explaining its non-psychoactive profile.

Reduced Synchronized Firing

Combined target effects lower network-wide hyperexcitability.

• ~45%: Hyperexcitability drop (simulated network)
• Reduced: Synchrony (fewer synchronized bursts)
• Gradual: Onset (weeks, not hours)
• Multi-target: Mechanism type (not single receptor)

Network desynchronization

Fewer neurons fire together, reducing the substrate for seizure spread.

Reduced synchrony, not silencing, is the proposed anticonvulsant effect.

Gradual trajectory

Effects build over weeks of consistent dosing, matching trial data.

Dose dependence

Higher CBD doses produce larger reductions in network excitability.

Seizure Frequency Reduction

Trials show meaningful seizure reduction in these refractory syndromes.

• ~40%: Seizure reduction (vs placebo add-on)
• 2: Approved syndromes (Dravet, LGS)
• None: Psychoactivity (unlike THC)
• Add-on: Therapy type (after AEDs fail)

Trial results

Randomized trials show significant convulsive seizure frequency reduction.

Approved specifically as add-on therapy for Dravet and Lennox-Gastaut.

Non-psychoactive

CBD lacks THC-like CB1 effects, sparing patients intoxication.

Ongoing use

CBD remains an option only when standard anti-epileptics have failed.

CBD vs THC — target comparison