This appears to be the first reported case of status epilepticus most plausibly driven by tetrahydrocannabinol (THC) ingestion in a pediatric patient. Pediatric patients are more susceptible to severe toxic effects due to smaller body mass, immature hepatic metabolism, and differing neurodevelopmental vulnerability [1,6,7]. In this case, the patient experienced persistent encephalopathy between seizures. Transient post-extubation tremors, primarily involving the upper extremities and jaw, may have reflected residual sedation, postictal activity, or persistent neuroexcitation from THC. These movements resolved spontaneously and were not associated with epileptiform EEG findings or MRI abnormalities, further supporting a nonstructural and reversible etiology. Because a toxicologic etiology was suspected, the care team prioritized benzodiazepines and supportive care over long-term antiepileptic drug loading. Although more potent synthetic cannabinoids such as Δ9-THCP have been described in the literature, these were not suspected given the parental report of conventional THC edibles in the home and absence of other exposure history. While the precise dose and source could not be confirmed, toxicologic analysis revealed a serum THC-COOH concentration of 256 ng/mL, far exceeding levels seen with recreational use [8]. This finding provides strong objective evidence of significant exposure.

THC exerts its effects as a partial agonist at cannabinoid type 1 (CB1) receptors, which are densely expressed in the cortex, hippocampus, and cerebellum. While low doses may suppress excitatory neurotransmission and appear anticonvulsant, high concentrations preferentially inhibit GABAergic signaling, leading to network disinhibition and increased seizure susceptibility. This biphasic profile has been demonstrated in both animal models and pediatric case series, where THC exposure was linked to heightened hippocampal excitability and reduced seizure threshold, particularly in immature neurons [6]. In a scoping review, cannabis exposure was associated with increased seizure incidence in 10 of 11 studies involving pediatric and general populations [7]. These findings suggest delta-9-THC may have proconvulsant properties in overdose.

THC is primarily metabolized by cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A4 [9]. These enzymes exhibit variable expression and activity in early childhood, leading to increased susceptibility to either accumulation or toxic metabolite production. Such variability may help explain the spectrum of pediatric presentations from mild sedation to status epilepticus.

Other causes of status epilepticus were reasonably excluded. Normal CSF protein and glucose, absence of nucleated cells, and negative cultures made bacterial and viral meningoencephalitis unlikely. Normal electrolytes, calcium, and glucose excluded metabolic precipitants. Normal EKG excluded dysrhythmias. Normal cerebral imaging excluded intracranial hemorrhage, developmental malformations, encephalitis, or brain malignancy. Negative blood cultures excluded bacteremia. Although benzoylecgonine was detected at 74 ng/mL by confirmatory LC/MS, the initial immunoassay signal was below the reporting threshold and a repeat screen four hours later was negative, raising doubt about the clinical significance of this finding. While seizures themselves can be considered part of the sympathomimetic toxidrome, this patient did not demonstrate persistent or escalating features such as hypertension, diaphoresis, mydriasis, or tachyarrhythmia that would typically support cocaine as a primary cause [10]. Combined with the absence of sustained sympathomimetic findings and the prolonged clinical course, these results make cocaine a less likely primary driver. However, because benzoylecgonine was confirmed on LC/MS and false positives are rare, co-exposure cannot be completely excluded. This interpretation is supported by the parental report that cannabis edibles were present in the home at the time of ingestion, providing a clear exposure source. 

Limitations include absent detailed seizure semiology and uncertainty regarding the THC dose or source of the edibles. Nonetheless, toxicologic confirmation with markedly elevated serum and urine THC-COOH supports substantial exposure. This case highlights the need for clinicians to include cannabis exposure in the differential diagnosis of new-onset pediatric seizures, even in the absence of a witnessed ingestion or known THC source.