What Caused Acute Encephalopathy in This Young Child?

A previously healthy 2-year-old girl presented to an emergency department about 45 minutes after a reported ingestion of cannabidiol gummies that left her sedated and in a minimally conscious state; she had arrived via air ambulance. Clinicians found her barely responsive to stimuli, with a Glasgow Coma Scale score of three.

Examination noted a weight of 15.3 kg (33.7 lb), a heart rate of 136 beats per minute, and an oxygen saturation of 98% on room air. Her acute encephalopathy raised concerns about potential airway compromise, and clinicians used fentanyl and ketamine to intubate the patient.

The patient continued to be slightly responsive; the medical team observed spontaneous eye opening and movements of her arms. She was given light sedation with dexmedetomidine drip at 0.5 mcg/kg/hour and admitted to the pediatric intensive care unit.

During consultation with toxicology service clinicians, the family reported having found the child lethargic and acting strangely, with the father noting that he purchased delta-8 tetrahydrocannabinol (THC) gummies from a local gas station and left them unopened on a desk. The family investigated and found three gummies on the floor, along with the open empty package, which had contained 12 gummies. The package label stated that each contained 25 mg of delta-8 THC.

The toxicology team estimated that the total dose ingested from nine gummies was 225 mg of delta-8 THC. The father reported that there were no other marijuana products in the home.

Clinicians used enzyme-linked immunoassay to perform an initial urine drug screen, which identified cannabinoids and fentanyl. Reflex liquid chromatography-tandem mass spectrometry (LC-MS/MS) detected fentanyl at 5 ng/mL and carboxy-THC at >400 ng/mL. Subsequent urine drug testing by gas chromatography-mass spectrometry was positive for ketamine, fentanyl, and cannabinoids. There was no evidence of abnormal findings revealed by the complete blood count and comprehensive metabolic panel.

Clinicians sent the child’s biological samples and the gummies to the Drug Enforcement Administration’s Toxicology Testing Program for analysis. Comprehensive analysis of the gummy using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) identified delta-8 THC and no evidence of delta-9 THC. Analysis of blood and urine samples revealed a plasma concentration of 107.6 ng/mL delta-8 THC and 746.5 ng/mL of 11-nor-9-carboxy-delta-8 THC, and a urine concentration of 1,550 ng/mL of 11-nor-9-carboxy-delta-8 THC.

About 10 hours after admission to the pediatric intensive care unit, the patient was extubated and kept under observation for another 24 hours. Her Glasgow Coma Scale score returned to 15, her level of alertness returned to normal, and she was able to eat and drink without trouble. Her mental impairment resolved within the next 24 hours. She was discharged home after her parents had a follow-up consultation with social workers and a pediatric forensic team.

Discussion

In this case of a child’s accidental exposure to delta-8 THC, clinicians noted that such occurrences are likely to increase with the growing availability of marijuana products. The marijuana plant contains both delta-9 THC and its isomer delta-8 THC, typically in lower concentrations.

Exposure to delta-9 THC is associated with symptoms ranging from difficulty moving and excessive sleepiness, to respiratory depression and seizures, according to reports. Differentiation of delta-8 THC from delta-9 THC is not readily achieved with routine lab testing, and because ingestion of the two has comparable clinical effects, it is difficult to identify which product was taken, the authors explained.

Although studies of the anticonvulsant and antiemetic properties of delta-8 THC began in the 1970s, “delta-8 THC has more recently gained popularity, with articles published in mainstream media,” the authors wrote.

Pharmacologically, both delta-8 THC and delta-9 THC activate the cannabinoid type 1 and type 2 receptors; however, their relative potency has not been well studied, the authors noted. A mouse study suggested near-equivalent potency of the two, and described “three progressive stages of exposure,” including irritability; a decrease in spontaneous activity, with hypersensitivity to auditory and tactile stimuli; and marked depression of spontaneous activity, decreased awareness, loss of muscle coordination, and reduced sensorimotor response.

In addition, exposure to delta-8 THC is associated with a greater likelihood of immobility, while exposure to delta-8 THC and delta-9 THC is associated with hypothermia and respiratory depression, they added.

Clinically, the psychoactive effects of delta-8 THC in children and adults are similar to those of delta-9 THC, the authors said; delta-8 THC demonstrated antiemetic properties in a small study of eight young cancer patients, with adverse effects of irritability in two patients and euphoria in one patient.

According to another small study in adults, oral or intravenous doses of delta-8 THC had an estimated potency ratio of 2:3 compared with delta-9 THC; however, both compounds “produced similar somatic, perceptual, and psychic effects,” the authors wrote.

The American Association of Poison Control Centers recently introduced a product code specific to delta-8 THC into its National Poison Data System to allow monitoring of adverse events. The FDA reported that of 661 cases of exposure to delta-8 THC products from January 1 to July 31 of this year, 41% were unintentional, and 77% of these exposures affected children. Eighteen percent of unintentional exposures required hospitalization, including children who required intensive care unit admission.

The case authors noted that symptomatic and supportive care are effective in the management of cannabinoid toxicity. Potential interventions include intravenous fluids and vasopressors for hemodynamic support, and benzodiazepines for patients with acute anxiety, agitation, or seizures. Obtaining drug samples, as well as blood and urine testing, may enhance future understanding of drug effects and best approaches to treatment, they added.

“There are no published case reports of delta-8 THC exposures to date nor has there been laboratory confirmation obtained,” the authors wrote. Complete documentation is impeded by lack of available confirmatory testing for delta-8 THC, its interaction with “other naturally occurring cannabinoids in standard immunoassays,” and the similar clinical effects of delta-8 THC and delta-9 THC exposures, they continued.

They cited a Driving Under the Influence of Drugs investigation, which confirmed the presence of delta-8 THC and its metabolites using a two-dimensional high-performance LC-MS/MS. “However, no method using LC-QTOF/MS, as applied in our case, has previously been published,” they wrote.

In conclusion, they cautioned that “current commercially available packaging and flavoring do little to deter children from ingesting these substances.”