To describe a case of hyperkinetic movements caused by accidental phenytoin toxicity due to cannabis use for self-treatment of insomnia.

Phenytoin is an antiseizure medication with a narrow dosing range due to near-saturation of its cytochrome metabolizers CYP2C19 and CYP2C9 causing transition to zero-order pharmacokinetics when total substrate exceeds available cytochrome activity. Cannabis products marketed as sleep aids contain increasing amounts of cannabidiol (CBD), a potent inhibitor of CYP2C19 and a competitive substrate of CYP2C19 and CYP2C9. Phenytoin has rarely been described causing movement disorders, usually dystonia due to inherent anticholinergic properties. In patients with altered pallidal structures, movement disorders are more frequently observed.

Case Report

A 66-year-old man with temporal lobe epilepsy on phenytoin for 44 years, cigarette smoking with 175 pack-year history, COPD on supplemental oxygen, and chronic insomnia began to smoke an over-the-counter cannabis sleep aid and subsequently developed acute-onset myoclonus followed by akathisia, asymmetric shoulder dystonia, and choreiform movements which abolished with sleep. Total/free phenytoin levels increased to 34.6 mcg/mL/2.79 mg/L from stable baseline 7.2 mcg/mL/0.72 mg/L 3 months prior to initiation of cannabis use. Hemoglobin was 18.6 g/dL with normal indices. MRI brain revealed pallido-nigro-rubral siderosis likely due to chronic hyperhemoglobinemia, atrophy of the cerebellar vermis, and bilateral hippocampal sclerosis without diffusion restriction or contrast enhancement. Nutritional, mineral, and autoimmune studies were normal. Following discontinuation of phenytoin, the myoclonus, akathisia, dystonia, and choreiform movements resolved.

Development and increasing availability of high-cannabinoid products increases the degree and frequency of potential drug-drug interactions. Cannabis use has the risk of causing phenytoin toxicity in previously stable patients. In patients with altered pallidal structures such as chronic siderosis or infarcts, phenytoin toxicity can initially manifest as hyperkinetic movement disorders, and its early recognition can save morbidity and mortality.