Cannabis and Levetiracetam (Keppra)
Brand names: Keppra, Keppra XR, Spritam, Roweepra
Important Medical Disclaimer
This information is for educational purposes only and does not constitute medical advice. Do not start, stop, or modify your use of Levetiracetam or cannabis without consulting your doctor or pharmacist. If you experience adverse effects, seek immediate medical attention. Individual responses to drug combinations vary significantly.
Overview
Levetiracetam is a widely prescribed anticonvulsant used for partial onset seizures, myoclonic seizures, and primary generalized tonic-clonic seizures. It has a unique mechanism of action, binding to synaptic vesicle protein SV2A to modulate neurotransmitter release. Cannabis, particularly CBD, has gained significant attention as an anticonvulsant in its own right, with FDA-approved CBD (Epidiolex) used for certain refractory epilepsy syndromes. The combination is considered low risk, though CBD may modestly alter levetiracetam levels. Many patients with epilepsy explore cannabis as a complementary therapy, particularly those with treatment-resistant seizures. Levetiracetam's favorable pharmacokinetic profile—minimal protein binding, predominantly renal elimination, and lack of CYP450 metabolism—makes it one of the safest anticonvulsants to combine with cannabis from a drug interaction perspective. However, the interaction is not negligible: clinical data from Epidiolex trials have shown modest increases in levetiracetam levels when combined with CBD, suggesting a non-CYP450 interaction mechanism. Additionally, the additive CNS effects of both substances warrant attention.
How They Interact
Levetiracetam has a unique pharmacokinetic profile that minimizes interaction risk: it undergoes minimal hepatic metabolism (not CYP450-dependent), has low protein binding (less than 10%), and is primarily eliminated unchanged through renal excretion. The minor hepatic metabolism involves enzymatic hydrolysis of the acetamide group, not CYP450 enzymes. Despite this, data from the Epidiolex clinical development program showed that CBD co-administration produced a modest 20-30% increase in levetiracetam plasma levels through a mechanism not fully characterized. This may involve competition for renal transporters or protein binding displacement. The pharmacodynamic interaction is potentially complementary for seizure control: levetiracetam modulates neurotransmitter release via SV2A binding, while CBD has anticonvulsant effects through GPR55 antagonism, TRPV1 modulation, and other mechanisms. THC's role in seizure management is less clear, with some preclinical evidence suggesting it can be either pro- or anti-convulsant depending on dose and seizure type.
Cannabinoid-Specific Interactions
| Cannabinoid | Interaction with Levetiracetam |
|---|---|
| THC | THC's effect on seizure threshold is uncertain—low doses may have anticonvulsant properties while higher doses or abrupt withdrawal may lower seizure threshold. THC adds CNS depression (drowsiness, dizziness) to levetiracetam's side effect profile. THC does not appear to significantly affect levetiracetam pharmacokinetics. |
| CBD | CBD has demonstrated anticonvulsant properties and may complement levetiracetam's seizure control through different mechanisms. Clinical data from Epidiolex trials show CBD can increase levetiracetam levels by 20-30%, possibly through non-CYP450 mechanisms. This increase is generally well tolerated but may amplify levetiracetam side effects like drowsiness and behavioral changes. |
Symptoms to Watch For
- ⚠Increased drowsiness from additive CNS effects
- ⚠Behavioral changes or mood disturbances (levetiracetam is known for irritability as a side effect, which may be modulated by cannabis)
- ⚠Dizziness and coordination impairment
Recommendations
- 1If adding CBD-containing cannabis to levetiracetam therapy, inform your neurologist so they can monitor levetiracetam levels and adjust dosing if needed.
- 2Watch for increased drowsiness, mood changes, or behavioral disturbances that may indicate elevated levetiracetam exposure from CBD co-administration.
- 3Do not adjust anticonvulsant medication dosing without medical guidance, even if you believe cannabis is providing additional seizure control.
- 4Keep a seizure diary that documents cannabis use alongside seizure frequency to help your neurologist assess the combination's effectiveness.
Research Summary
Levetiracetam-CBD interaction data comes primarily from the Epidiolex clinical development program. Pooled pharmacokinetic analysis showed that CBD increased steady-state levetiracetam concentrations by approximately 20-30%, though this was not associated with increased adverse events in the trial populations (primarily children and young adults with Dravet syndrome and Lennox-Gastaut syndrome). The mechanism of this interaction remains under investigation, as it does not appear to involve CYP450 enzymes. A 2019 retrospective analysis of pediatric epilepsy patients using artisanal CBD products alongside levetiracetam reported improved seizure control in a subset without significant safety concerns. Regarding THC, a 2020 review in Epilepsy & Behavior noted mixed evidence for THC's effects on seizure threshold and recommended caution, particularly with inconsistent dosing. The overall evidence supports levetiracetam as one of the lower-risk anticonvulsants to combine with cannabis products.
Frequently Asked Questions
Can CBD help control seizures that Keppra alone doesn't manage?
CBD has demonstrated efficacy for certain treatment-resistant epilepsy syndromes, particularly Dravet syndrome and Lennox-Gastaut syndrome. Some patients experience improved seizure control when CBD is added to levetiracetam, but this should be done under neurological supervision with appropriate monitoring of drug levels and seizure frequency.
Does cannabis affect my Keppra blood levels?
Yes, CBD has been shown to modestly increase levetiracetam blood levels by 20-30% in clinical studies. This increase is usually well tolerated but may contribute to increased side effects. THC does not appear to significantly affect levetiracetam levels. If you use cannabis regularly, your neurologist may want to check your levetiracetam levels.
Is it safe to use cannabis if I have epilepsy?
This depends on the type of cannabis, the type of epilepsy, and your current medication regimen. CBD has proven anticonvulsant effects and is FDA-approved for certain epilepsy syndromes. THC's effects on seizures are less clear and potentially risky with inconsistent dosing. Always consult your neurologist before using cannabis with epilepsy medications.
Can I replace Keppra with cannabis for seizure control?
Do not discontinue levetiracetam or any anticonvulsant without neurological supervision. Abrupt discontinuation can cause seizure recurrence or status epilepticus, which is a medical emergency. While CBD has anticonvulsant properties, it is typically used as adjunctive therapy rather than a replacement for established anticonvulsants.