Tetrahydrocannabinol-Containing Sleep Aid Supplements: An Unexpected Cause of Drug-Induced Liver Injury

Introduction: Marijuana is the most commonly used federally illicit drug in the United States. Tetrahydrocannabinol (THC) is the active chemical component responsible for marijuana's desirable clinical effects. THC-containing products are often used without a prescription from a licensed medical provider for the treatment of several medical conditions, including insomnia. Certain THC-containing products marketed in the U.S. are formulated with other ingredients which may potentially cause liver failure. Here we report a case of liver injury due to the use of sleep aid pills marketed in the U.S. as Midnight Drop. Case Description/Methods: A 53-year-old woman presented to our hepatology clinic for evaluation of elevated liver enzymes. Previously her liver biochemical profile was normal. On presentation, she reported right upper quadrant abdominal pain. Medical history was pertinent for alcohol use of 2-3 glasses of wine daily, and family history significant for autoimmune diseases including rheumatoid arthritis and giant cell arthritis. She reported taking THC supplements for insomnia. Liver enzymes on initial presentation are shown below (Table 1). Abdominal ultrasound showed gallbladder sludge but otherwise a liver with normal hepatic parenchyma. Our initial impression was liver injury secondary to alcohol use, autoimmune hepatitis, and drug-induced liver injury (DILI). Subsequently, blood testing was positive only for antinuclear antibodies (>1:1280). A liver biopsy showed hepatic parenchyma with multifocal centrilobular hepatocyte dropout and portal/pericentral ceroid-laden macrophages, suggestive of resolving recent liver injury and mild nonspecific lobular and portal inflammation (Figure 1). Based on the biopsy findings, the ingredients of the THC-containing supplement were analyzed and found to contain corydalis extract, which has been identified as a cause of liver injury in very recent literature. On further questioning, the onset of the abdominal pain and liver enzyme elevations correlated very well with the start of the THC supplement, so we recommended stopping taking it. Repeat liver enzymes following discontinuation of Midnight Drop showed significant improvement in liver enzymes as demonstrated below (Table 1). Discussion: Here we present a case of liver injury due to THC supplements. Although THC supplements have not been reported to be hepatotoxic, clinicians should be aware that different formulations might include hepatotoxic ingredients.Figure 1.: Liver biopsy slides of findings consistent with Drug induces liver injury (DILI). (a) Periportal ceroid-laden macrophages; (b) Periportal inflammation; (c) Hepatocellular dropout. Table 1. - Liver enzymes on initial presentation and after discontinuation of the THC supplement Reference range and units Initial results Results 80 days later Total Bilirubin 0.00 - 1.60 mg/dL 0.35 mg/dL 0.31 mg/dL ALP 35 – 104 UI/L 76 UI/L 128 UI/L ALT 10 – 35 UI/L 190 UI/L 40 UI/L AST ≤32 UI/L 342 UI/L 66 UI/L