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Background Kratom is an herbal supplement containing alkaloids with opioid properties. This review was conducted to determine toxicities associated with kratom use in the United States in order to provide insight into its safety as a dietary supplement. Methods We conducted a retrospective review of kratom exposures reported to the National Poison Data System to determine the toxicities associated with kratom use. We also reviewed records from a county medical examiner's office in New York State to identify kratom‐associated fatalities. Results A total of 2312 kratom exposures were reported, with 935 cases involving kratom as the only substance. Kratom most commonly caused agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), and confusion (8.1%). Serious effects of seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%) were also reported. Kratom was listed as a cause or contributing factor in the death of four decedents identified by the county medical examiner's office. Conclusions Kratom use is increasing and is associated with significant toxicities. Our findings suggest kratom is not reasonably expected to be safe and poses a public health threat due to its availability as an herbal supplement.

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Loperamide is an over-the-counter antidiarrheal with opioidreceptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for selftreatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.A New York case of loperamide abuse was defined as any call to the Upstate New York Poison Center or New York City Poison Control Center reporting intentional loperamide abuse during January 1, 2008-March 31, 2016. An NPDS loperamide abuse case was defined as any exposure reported to NPDS citing intentional loperamide abuse during January 1, 2008-March 31, 2016.Among the 22 New York loperamide abuse cases identified, 18 patients were male. Median patient age was 30 years (range = 19-48 years). Electrocardiogram abnormalities included QTc prolongation in 15 (68%) patients, QRS prolongation in nine (41%) patients, and ventricular dysrhythmia in eight (36%) patients. The average reported daily dose was 358 mg (range = 34-1,200 mg). Previous opioid abuse was reported by 15 patients, previous treatment with methadone or buprenorphine (a partial opioid agonist used to treat opioid addiction) by eight patients, and chronic abuse by 13 patients. Opioid withdrawal symptoms after cessation of loperamide were reported by nine patients. Serum loperamide concentrations were obtained from four patients and ranged from 77-210 ng/mL, representing 25-875 times the therapeutic range of 0.24-3.1 ng/mL (6).A total of 179 NPDS cases were identified, approximately half of which were reported after January 1, 2014 (Figure). Notes from the FieldAmong the 179 cases, 137 (77%) of the patients were male, the median patient age was 26 years (range = 7-87 years), and 154 (86%) were admitted to or treated in a health care facility. The average loperamide dose was 196.5 mg (range = 2-1,200 mg), and nearly all cases (95%) involved tablets or capsules. Cardiac conduction disturbances were reported in 24 (13%) patients, ventricular tachycardia or fibrillation in 16 (9%) patients, other dysrhythmias in 10 (6%) patients, and other electrocardiogram changes in five (3%) patients. Outcome was reported for 132 patients and was coded as moderate (pronounced or prolonged systemic symptoms, non-life threatening) or major (life-threatening symptoms or residual disability) for 66 patients (50%). Four (3%) deaths were reported.These cases support the reported ass...

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The hERG IC50:C ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C ratio for clinical decision making in instances of drug selection where TdP risk is a concern.