Is it safe to use cannabis with Keppra (levetiracetam) for a 31-year-old female with catamenial epilepsy and nocturnal seizures?

Cannabis Use with Levetiracetam in Catamenial Epilepsy

Cannabis use alongside Keppra (levetiracetam) carries significant risks that outweigh potential benefits for this patient, primarily due to unpredictable drug interactions, lack of quality control in cannabis products, and the potential for cannabis to worsen seizure control despite anecdotal reports of benefit.

Primary Safety Concerns

Drug Interaction Profile

• Levetiracetam has minimal drug interactions and does not require cardiac monitoring, making it a preferred antiepileptic agent 1, 2
• However, cannabis contains hundreds of bioactive compounds with variable concentrations depending on strain, and these can affect seizure threshold unpredictably 3, 4
• The psychoactive component THC may lower seizure threshold in some individuals, while CBD may have anticonvulsant properties, but most recreational cannabis products contain predominantly THC with minimal CBD 4, 5

Cannabis Effects on Seizure Control

• Anecdotal reports suggest that cessation of cannabis use in some individuals precipitates re-emergence of seizures, while resumption controls epilepsy in a reproducible manner 5
• However, scientific evidence shows that THC acts via cannabinoid receptor CB1 and can have proconvulsant effects, while CBD's mechanism is unclear but likely polypharmacological 4
• Recent clinical trials with over 100 participants showed CBD resulted in significant seizure frequency reduction, but these studies used pharmaceutical-grade CBD in adjunct with antiepileptic medications, not recreational cannabis 3

Specific Risks for This Patient

Nocturnal seizure pattern considerations:

• Cannabis causes sedation, drowsiness, and disorientation in 19%, 10%, and 3% of users respectively 6
• These sedative effects could mask warning signs of nocturnal seizures or impair the patient's ability to recognize seizure activity 6

Catamenial epilepsy considerations:

• Catamenial epilepsy affects approximately one-third of women with epilepsy and is influenced by hormonal fluctuations 7
• Progesterone has anticonvulsant properties while estrogen has proconvulsant effects 7
• Cannabis effects on hormonal regulation are not well-characterized in the context of catamenial epilepsy, creating additional unpredictability 7

Current medication adequacy:

• This patient is on 1000 mg Keppra once daily, which is suboptimal dosing—each 1000 mg increase in levetiracetam dose raises odds of response by 40%, and 500 mg/day is NOT more effective than placebo 2
• The seizures may be inadequately controlled due to insufficient levetiracetam dosing rather than requiring cannabis supplementation 2

Clinical Recommendations

Immediate Actions

• Optimize levetiracetam dosing first before considering any adjunctive therapy—standard maintenance dosing is 1500-3000 mg daily in divided doses 8, 2
• For this patient with nocturnal seizures, consider splitting the dose to 1000 mg twice daily or increasing to 1500 mg at bedtime 8
• Monitor for psychiatric side effects, as levetiracetam causes behavioral changes in 23% of patients 2

Cannabis-Specific Guidance

• If the patient insists on continuing cannabis use, strongly advise against it during the medication optimization period to accurately assess levetiracetam efficacy 1, 2
• Explain that recreational cannabis products lack standardization, quality control, and consistent CBD:THC ratios, making them unreliable for seizure management 3, 4
• Cannabis has clear negative effects on the developing and mature brain, though these appear relatively mild in most cases 4

Alternative Approaches for Catamenial Epilepsy

• Consider cyclical use of benzodiazepines, acetazolamide, or hormonal therapy specifically for catamenial patterns if seizures persist despite optimized levetiracetam 7
• Lamotrigine has shown 66% efficacy in catamenial epilepsy (defined as seizure disappearance or ≥50% reduction) and was found to raise serum progesterone levels during treatment 9
• Maintain careful menstrual and seizure diaries to characterize whether the pattern is perimenstrual, periovulatory, or luteal 7

Critical Pitfalls to Avoid

• Do not assume that because the patient used cannabis before seizures began that it is safe to continue—the presence of epilepsy fundamentally changes the risk-benefit calculation 4, 5
• Do not accept "it helps me sleep" as justification for continued use—address sleep hygiene and consider melatonin or other non-cannabis sleep aids that won't affect seizure threshold 6
• Do not skip optimization of conventional antiepileptic therapy in favor of unproven cannabis products 1, 8
• Avoid the misconception that all cannabis is equivalent—pharmaceutical-grade CBD products used in clinical trials are fundamentally different from recreational cannabis 3, 4

Monitoring Requirements if Cannabis Use Continues Despite Counseling

• Maintain detailed seizure diary documenting frequency, timing relative to cannabis use, and menstrual cycle 7
• Monitor for increased seizure frequency, changes in seizure pattern, or emergence of psychiatric symptoms 2, 4
• Check levetiracetam levels if seizure control worsens to rule out non-adherence versus true drug interaction 8
• Counsel patient to avoid driving and ensure she adheres to national guidelines regarding epilepsy and driving competency 6