Toxicity related to THC dose in pediatric edible cannabis ingestions

The dose of tetrahydrocannabinol (THC) in pediatric edible ingestions correlated to the degree of toxicity in children younger than 6 years, according to a study published August 28, 2023, in Pediatrics.

Over the last 10 years, pediatric exposures to cannabis products have increased, a consequence of increased legalization in North America. In the same timeframe, increased concentrations of δ-9 THC, the primary psychoactive cannabinoid, have also been observed. Pediatric ingestions of marijuana can lead to drowsiness, ataxia, vomiting, and tachycardia, while more common findings are coma, hypotension, respiratory depression, and seizure, which occur in less than 3.5% of cases, according to the study. Only a “small” proportion of children that are evaluated in a hospital following a cannabis ingestion require intensive care admission or invasive supportive measures, like intubation. The THC dose in young children likely leads to a correlation of toxicity, but investigators sought to determine, “what dose predicts a severe clinical course,” and to characterize clinical toxicity to THC dose after an edible ingestion has occurred.

The study is a retrospective review of children younger than 6 years who presented to a pediatric hospital network with edible cannabis ingestions of known THC dose from January 1, 2015, to October 25, 2022. The location took place at a pediatric hospital network located in an urban area of a state with legal recreational and medicinal cannabis. Four inpatient pediatric hospitals with emergency departments (EDs) and 3 urgent care centers were included in the network, which provided services to an average of 156,880 annual visits during the study period, not including 2022.

To be included, patients had to be younger than 6 years of age with a known THC dose, determined by the caregiver or guardian. State regulations required clear and accurate THC dose in milligrams on the recreational cannabis products’ labels. Cases without documented labeling were excluded. Further, patients were excluded if they ingested a nonedible preparation, had a prescription for medicinal cannabis, or if they had a non-ingestion route of exposure. Symptom resolution was classified as when the participant was documented to be at their baseline or documentation of normal behaviors for the age of the child. Severe toxicity was if participants demonstrated severe cardiovascular, respiratory, or neurologic effects. These cardiovascular effects included requiring vasopressors in intravenous fluids, bradycardia, tachycardia/hypotension, or other dysrhythmias. Respiratory effects included apnea, respiratory failure, and required oxygen supplementation. Seizure, unresponsiveness, myoclonus, responsiveness only to painful stimulation, required sedated medication, or required intubation were neurologic effects. Prolonged cannabis toxicity was defined as patients that required more than 6 hours to reach baseline.

The mean age of the 80 patients that met inclusion criteria was 2.9 years, and the median ingestion of THC was 2.1 mg / kg. There were 37 patients in which severe toxicity was present (46%), with a mean ingested THC dose of 5.4 mg/kg, lasting for a median of 20.3 hours. Twenty-one of these cases (57%) were a result of ingestion of gummy edibles, while neurologic effects accounted for 28 (76%) of these presentations. In 31 (41%) of patients, onset to severe toxicity could be estimated, with a median onset within 2.3 hours (interquartile range [IQR] 1.3-3.8). Prolonged toxicity was observed in 57 (74%) of patients, with a median ingested THC dose of 3.7 mg / kg (IQR 1.7-5.7).

Investigators determined severe THC dose was a “significant predictor” of severe (adjusted odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.8–4.7) and prolonged (OR 3.2, 95% CI: 1.6–6.5) toxicity, but age and sex were not. According to the authors, “Receiver operator characteristic (ROC) curve and area under the curve (AUC) analyses were used to estimate the ingested weight-based THC dose threshold with the highest sensitivity and specificity to independently predict severe toxicity and prolonged toxicity.” Results demonstrated AUC was 92.9% for severe toxicity and 87.3% for prolonged toxicity. THC ingestions of 1.7 mg / kg or more can predict severe and prolonged toxicity, according to the authors (sensitivity 97.3% and 75.4% respectively). This threshold could be used to guide medical management and preventive regulations, the authors concluded.

Reference:

Pepin LC, Simon MW, Banerji S, Leonard J, Hoyte CO, Wang GS. Toxic tetrahydrocannabinol (THC) dose in pediatric cannabis edible ingestions. Pediatrics September 2023; 152 (3): e2023061374. 10.1542/peds.2023-06137