Can marijuana lower the seizure threshold in individuals with a history of seizure disorders?

Can Marijuana Lower the Seizure Threshold?

The relationship between marijuana and seizure threshold is complex and bidirectional: while pharmaceutical-grade CBD (Epidiolex) has proven antiepileptic effects for specific rare epilepsy syndromes, whole-plant cannabis/marijuana can paradoxically both lower and raise seizure threshold depending on the formulation, dose, and individual patient factors. 1, 2

Key Evidence from Guidelines

Substances That Lower Seizure Threshold

• Illicit substance use, including cocaine, can lower the seizure threshold, as recognized by the American College of Emergency Physicians in their 2024 clinical policy on seizure management. 1

• Marijuana or its constituents can lower the seizure threshold in some animal models, though human data remains inconclusive. 3

• Marijuana use or withdrawal could potentially trigger seizures in susceptible patients, particularly those with pre-existing seizure disorders. 3

The Paradoxical Nature of Cannabis

• Whole-plant cannabis can paradoxically both contribute to and reduce seizures, which is why its use is not recommended due to lack of standardization, quality control, and rigorous efficacy data. 2

• Some evidence suggests marijuana and its active cannabinoids have antiepileptic effects, but these may be specific to partial or tonic-clonic seizures, while in other contexts they may lower seizure threshold. 3

Critical Distinctions in Cannabis Products

FDA-Approved vs. Recreational/Medical Marijuana

• Only pharmaceutical-grade CBD (Epidiolex) is FDA-approved for epilepsy, specifically for Dravet Syndrome, Lennox-Gastaut Syndrome, and tuberous sclerosis complex-associated seizures at doses of 5-25 mg/kg/day. 2

• Medical marijuana itself has not been FDA-approved for any indication, despite state legalization programs, and remains federally classified as Schedule I with "no currently accepted medical use." 4

• The potency of cannabis products has dramatically increased, with THC concentration nearly doubling from 9% in 2008 to 17% in 2017, and concentrates reaching 70% THC, which elevates all health risks including seizure precipitation. 5

Clinical Implications for Patients with Seizure History

Risk Factors to Consider

• Patients with a history of seizure disorders face uncertain risk when using marijuana, as the evidence shows both potential benefit and harm depending on multiple factors. 3, 6

• In one Canadian study of epilepsy patients, 5 patients reported possible seizure precipitation from marijuana use, though 84% of epilepsy patients perceived improvement in seizures. 6

• Marijuana use can transiently impair short-term memory and may increase noncompliance with antiepileptic drugs, indirectly increasing seizure risk. 3

Drug Interactions

• CBD significantly interacts with multiple antiepileptic drugs through CYP450 inhibition, requiring dose adjustments particularly for clobazam and valproate. 2

• Antipsychotic medications lower seizure threshold in a dose-dependent manner, and combining these with marijuana could theoretically compound risk. 1

Practical Clinical Approach

Assessment Points

• Obtain detailed history of cannabis product type (whole-plant marijuana vs. pharmaceutical CBD), THC/CBD content, dose, frequency, and route of administration when evaluating seizure risk. 2, 7

• Inquire about withdrawal patterns, as marijuana withdrawal could potentially trigger seizures similar to alcohol withdrawal effects. 3

• Screen for concomitant substance use, particularly alcohol and tobacco, which commonly co-occur with marijuana use in epilepsy patients. 6

Risk Stratification

• Highest risk patients include those with:
  • Pre-existing seizure disorders using high-THC products 5
  • Concurrent use of medications that lower seizure threshold 1
  • History of substance abuse or withdrawal seizures 1
  • Use of unstandardized whole-plant cannabis products 2

Management Recommendations

• For patients with epilepsy considering cannabis, only pharmaceutical-grade CBD (Epidiolex) should be recommended, and only after failure of standard therapies in FDA-approved indications. 2

• Whole-plant marijuana should not be recommended for seizure management due to lack of standardization and potential to both help and harm. 2

• If patients are using marijuana despite counseling, monitor closely for seizure frequency changes, ensure compliance with prescribed antiepileptic drugs, and adjust AED doses as needed for drug interactions. 2, 3

Special Populations at Higher Risk

• Pregnant and breastfeeding individuals must avoid all cannabis products due to fetal neurodevelopmental risks and increased premature birth risk. 2

• Adolescents face elevated risks including neurodevelopmental decline, psychotic disorders, depression, and suicidal ideation with cannabis use. 2

• Older adults using cannabis face higher risk for behavioral health issues, sedation, obtundation, and myocardial ischemia. 4