Can medical cannabis (cannabis containing tetrahydrocannabinol (THC)) cause seizures in individuals with a pre-existing seizure disorder or history of substance abuse?

Medical Cannabis Can Cause Seizures

Medical cannabis containing THC can paradoxically both lower and raise seizure threshold depending on formulation, dose, and individual patient factors, with high-THC products posing particular seizure risk in vulnerable populations including those with pre-existing seizure disorders and substance abuse history. 1, 2

Critical Distinction Between Cannabis Products

The relationship between cannabis and seizures is bidirectional and depends entirely on product composition:

• Only pharmaceutical-grade CBD (Epidiolex) is FDA-approved for epilepsy treatment (Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex) at doses of 5-25 mg/kg/day 3, 1
• Medical marijuana itself has NOT been FDA-approved for any indication despite state-level legalization programs, and remains federally classified as Schedule I with "no currently accepted medical use" 3, 2
• Whole-plant cannabis can both contribute to and reduce seizures, making its use problematic without standardization and quality control 1, 2

Evidence That THC-Containing Cannabis Can Cause Seizures

Case Reports and Clinical Evidence

• A 17-year-old with no prior seizure history developed a generalized tonic-clonic seizure after daily vaping of highly concentrated THC ("wax"), with EEG showing bifronto-centrally predominant sharp and spike wave discharges that resolved 7 days after cessation 4
• Thirty patients experienced seizures within 24 hours of synthetic cannabinoid use, with 90% presenting with tonic-clonic seizures and 46% having seizures within 30 minutes of inhalation 5
• A 44-year-old with 26 years of regular marijuana smoking developed late-onset epilepsy with brain MRI showing abnormal signal intensities in the right frontal lobe and basal ganglia 6

Mechanism of Seizure Provocation

• THC inhibits GABAergic inhibitory neurons, leading to excessive glutamate release and excitotoxic damage through glutamate excitotoxicity, the primary mechanism of neurotoxicity 7
• Cannabis concentrates with THC levels up to 70% pose substantially higher seizure risk than traditional plant material, with average THC concentration nearly doubling from 9% in 2008 to 17% in 2017 1, 2, 7

Highest Risk Populations

Patients with pre-existing seizure disorders using high-THC products face compounded risk through multiple mechanisms 1:

• Concurrent use of medications that lower seizure threshold (antipsychotics, certain antidepressants) compounds risk 1
• History of substance abuse or withdrawal seizures increases vulnerability 1
• Use of unstandardized whole-plant cannabis products with unpredictable THC content creates unpredictable seizure risk 2

Special Population Warnings

• Adolescents face elevated risks including neurodevelopmental decline and should avoid cannabis use entirely, with early initiation (before age 18) causing persistent neuropsychological deficits 1, 2, 7
• Pregnant and breastfeeding individuals must avoid all cannabis products due to fetal neurodevelopmental risks and increased premature birth risk 1, 7
• Older adults using cannabis face higher risk for sedation, obtundation, and myocardial ischemia 1, 7

Clinical Approach to Seizure Risk Assessment

When evaluating seizure risk in cannabis users, obtain:

• Detailed history of cannabis product type (whole-plant marijuana vs. pharmaceutical CBD) 1
• THC/CBD content, dose, frequency, and route of administration 1
• Timing of seizure relative to cannabis use (seizures within 30 minutes to 24 hours suggest provocation) 5, 4
• Concomitant medications that may interact or lower seizure threshold 1

Management Recommendations

For Patients with Epilepsy

Only pharmaceutical-grade CBD (Epidiolex) should be recommended, and only after failure of standard therapies in FDA-approved indications 1, 2:

• Whole-plant marijuana should NOT be recommended for seizure management due to lack of standardization and potential to both help and harm 1
• CBD significantly interacts with multiple antiepileptic drugs through CYP450 inhibition, requiring dose adjustments particularly for clobazam and valproate 1
• Counsel patients with epilepsy to avoid recreational cannabis products due to unpredictable THC content and paradoxical seizure risk 2

For Patients Using Cannabis Who Develop Seizures

• Monitor for worsening symptoms if patients are using cannabis therapeutically—consider dose reduction or discontinuation if seizures increase 2
• Recognize that seizure recurrence rate after cannabis-provoked seizures is similar to other acute systemic insults, with 9 of 24 patients (37.5%) experiencing subsequent seizures in one series 5
• Extended EEG may show epileptiform discharges that resolve with cessation, as demonstrated in the adolescent case where interictal findings resolved within 7 days 4

Critical Clinical Pitfalls

• Do not assume all cannabis products are equivalent—the distinction between high-CBD pharmaceutical products and high-THC recreational products is critical for seizure risk 1, 2
• Unintentional pediatric exposures increased from 207 cases in 2017 to 3,054 in 2021, with some causing central nervous system depression and seizures 2
• Cannabis use disorder develops in approximately 10% of chronic users, with withdrawal symptoms that can themselves lower seizure threshold 7
• The neurotoxic effects are not reversible in many cases, particularly when exposure occurs during critical neurodevelopmental periods 7