The relationship between cocaine use and seizures is complex. The mode of intake greatly affects seizure threshold. Inhaled (smoking of crack) or intravenously injected use is associated with de novo generalized seizures. Insufflated (snorted) use is associated with partial or idiopathic seizures.93 Massive overdoses like those associated with the rupture of cocaine-containing condoms being used for smuggling (body packers) usually do not include seizures.94 In patients who are delirious from cocaine poisoning, benzodiazepines are useful and safer than neuroleptics, which can cause neuroleptic malignant syndrome.94

The mechanism of epileptogenesis is still uncertain. Variable seizure rates relate to the frequency and mode of cocaine administration, with consequent variation in peak levels of the drug. Kindling of seizures has been described in rat models. Effects on the major excitatory neurotransmitter systems that are mediated by action at NMDA and AMPA receptors affect seizure induction in rats,95 but other chemicals, such as polyamines, are also changed in animals who develop seizures after repeated cocaine injection.96 Dopamine, implicated in the euphoric and addictive effects of cocaine, is probably not involved in seizures, but these effects do correlate with greater binding of cocaine at serotonin receptors than at muscarinic and cholinergic receptors.97 Other studies suggest that activity at the GABAA channel receptor leads to abnormal excitation and seizures.98

Isolated seizures do not require treatment. Any anticonvulsant is effective for patients with both cocaine-induced and spontaneous seizures. Because many cocaine abusers are poorly compliant with medication regimens, care must be used before initiating treatment, even in those with underlying seizure disorders exacerbated by cocaine.102 Patients who drink alcohol or use benzodiazepines to regulate their cocaine high may require protection from withdrawal seizures or delirium tremens, as well as from seizures associated with cocaine intoxication.103

Rarely, cocaine abusers report enhancing their high by opening phenytoin capsules and smoking it along with cocaine, which can lead to phenytoin toxicity.99 Early reports that phenytoin can reduce relapse rates in cocaine detoxification programs100 have not been confirmed.101

Adapted from: Koppel BS. Contribution of drugs and drug interactions (prescribed, over the counter, and illicit) to seizures and epilepsy. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;155–173. With permission from Elsevier (

Authored By: 
Barbara S. Koppel MD
Reviewed By: 
Steven C. Schachter MD
Monday, March 1, 2004