Is marijuana effective for seizure control in individuals with epilepsy?

Marijuana and Seizures: Evidence-Based Guidance

Direct Answer

FDA-approved cannabidiol (CBD) is effective for specific rare epilepsy syndromes, but whole-plant marijuana/cannabis is not FDA-approved for seizure control and carries significant risks that may outweigh uncertain benefits. 1, 2

FDA-Approved Cannabinoid for Epilepsy

Epidiolex (pharmaceutical-grade CBD) is the only cannabis-derived medication with FDA approval for epilepsy treatment. 1, 2 This approval is limited to three specific conditions:

• Dravet Syndrome - randomized controlled trials demonstrated significant seizure reduction compared to placebo 2, 3
• Lennox-Gastaut Syndrome - controlled trials showed significant improvement in seizure frequency 2, 3
• Tuberous sclerosis complex-associated seizures 1, 2

The typical dosing is 5-25 mg/kg/day administered twice daily, with dose-related, reversible transaminase elevations occurring in approximately 13% of patients, typically within the first 2 months 4

Critical Distinction: Medical Marijuana vs. FDA-Approved CBD

Medical marijuana itself has never received FDA approval for any indication, despite state-level legalization programs. 1, 5 Cannabis remains federally classified as Schedule I with "no currently accepted medical use" and "high potential for misuse." 1, 5

Key Differences:

• Pharmaceutical CBD (Epidiolex): Highly purified, standardized dosing, proven efficacy in controlled trials 2, 3
• Artisanal/dispensary cannabis products: Variable potency, uncontrolled THC content, lack of rigorous clinical trial data 3, 6

Evidence for Whole-Plant Cannabis in Epilepsy

Observational Data (Lower Quality Evidence):

Studies of patients using recreational/medical marijuana show:

• Perceived improvement: 84% of epilepsy patients reported subjective seizure improvement, though this was uncontrolled and may reflect stress reduction rather than direct anticonvulsant effects 7
• High usage rates: 57-64% of patients with uncontrolled epilepsy report marijuana use 7, 6
• Dosing uncertainty: Only 2 of 39 patients could provide exact dosing in milligrams 6

These observational studies cannot establish causation and are confounded by placebo effects, stress reduction, and variable product composition. 7, 8

Significant Safety Concerns

Seizure Precipitation Risk:

Whole-plant cannabis can paradoxically both contribute to and reduce seizures. 8 Five patients with epilepsy reported possible seizure precipitation from marijuana use 7

Hepatotoxicity with CBD:

• Liver enzyme monitoring is essential - meta-analysis showed 6-fold increase in liver enzyme elevation with CBD use 4
• No cases reported with total CBD doses <300 mg/day 4
• Risk increases with concomitant valproate - many patients with transaminase elevations were taking valproate simultaneously 3

Drug-Drug Interactions:

CBD significantly interacts with multiple antiepileptic drugs through CYP450 inhibition: 3

• Clobazam: CBD inhibits CYP2C19, significantly increasing N-desmethylclobazam levels and causing sedation 3
• Valproate: Increased risk of hepatotoxicity when combined 3
• Other interactions: Rufinamide, zonisamide, topiramate, eslicarbazepine, and warfarin 3

Cannabis Potency Concerns:

THC concentrations have nearly doubled from 9% (2008) to 17% (2017), with concentrates reaching 70% THC, dramatically increasing all health risks. 9

Standard Antiepileptic Drug Therapy Remains First-Line

For convulsive epilepsy, monotherapy with standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproic acid) should be offered first. 4 Cannabinoids should only be considered after failure of standard therapies and only in FDA-approved indications.

Post-Cardiac Arrest Seizure Management

For seizures in other contexts (e.g., post-cardiac arrest), treat with sodium valproate, levetiracetam, phenytoin, benzodiazepines, propofol, or barbiturates - not cannabis products. 4 Prophylactic anticonvulsant drugs are not recommended due to poor response rates and adverse effects 4

Clinical Algorithm for Cannabis/Cannabinoid Use in Epilepsy

1. Confirm diagnosis: Dravet Syndrome, Lennox-Gastaut Syndrome, or tuberous sclerosis complex 2
2. Document treatment-resistant epilepsy: Failure of at least two standard antiepileptic drugs 3
3. Use only FDA-approved pharmaceutical CBD (Epidiolex) - not dispensary products 1, 2
4. Baseline liver function tests before initiating CBD 4
5. Monitor transaminases monthly for first 2 months, then periodically 4
6. Review all concomitant medications for CYP450 interactions, particularly clobazam and valproate 3
7. Start low, titrate slowly to minimize adverse effects 4

Common Pitfalls to Avoid

• Do not recommend dispensary cannabis products - these lack standardization, quality control, and rigorous efficacy data 3, 6
• Do not assume patient-reported "CBD oil" is pharmaceutical-grade - most dispensary products contain variable THC and CBD ratios 6
• Do not ignore drug interactions - CBD is a potent CYP450 inhibitor requiring dose adjustments of other medications 3
• Do not skip liver monitoring - hepatotoxicity is dose-dependent and potentially serious 4
• Do not use in pregnancy - all cannabis products carry fetal brain development risks 1, 5

Populations Requiring Absolute Avoidance

Pregnant and breastfeeding individuals must avoid all cannabis products due to fetal neurodevelopmental risks and increased premature birth risk. 1, 5 Adolescents face elevated risks including neurodevelopmental decline, psychotic disorders, depression, and suicidal ideation 1, 5