Stephen L. Thornton

Synthetic cannabinoid use associated with acute kidney injury

The use of synthetic cannabinoids has been associated with multiple adverse effects, including seizures and psychosis. 1 Possible nephrotoxic effects from synthetic cannabinoid use have recently been reported. 2 We report a case of acute kidney injury (AKI) associated with the use of a synthetic cannabinoid product. A previously healthy 26-year-old male was presented to the emergency department with one day of abdominal pain, nausea, vomiting and lower back pain. His vital signs on arrival demonstrated a temperature of 97.7 ° F, heart rate of 54 beats per minute, blood pressure 151/40 mmHg, and respiratory rate of 16 breaths per minute with a SatO 2 of 100% on room air. His physical exam was unremarkable. He denied the use of ibuprofen or any other medication. He also denied using any herbal medications. He admitted to regular tobacco use but denied alcohol use. He did admit to smoking a product that he had obtained via the internet called “ Mr. Happy ” . He stated that he used this product two or three times a day for approximately one year and had used the product on the morning of his presentation. He denied any prior episodes of pain, vomiting, or agitation with the use of this product. Laboratory evaluation proved to be remarkable for a 14.4 K/mm3 WBC, 5.38 mg/dL serum creatinine, 30 mg/dL blood urea nitrogen (BUN), and urinalysis with 1+ protein and trace blood. His hemoglobin, platelets, electrolytes and total creatine kinase (CK) were normal. A urine immunoassay drug screen turned out to be negative. He was admitted to the hospital for further evaluation. The results of an antinuclear antibody titer turned out to be negative. A renal ultrasound was interpreted as normal and a renal biopsy demonstrated rare globally sclerotic glomeruli without evidence of acute glomerular disease. On Day 2 in the hospital, his creatinine and BUN peaked at 7.74 and 39 mg/dL, respectively. He was discharged after six days in the hospital with AKI of unknown etiology and serum creatinine of 3.09 mg/dL. Twenty three days later his serum creatinine was 1.1 mg/dL. He denied any further use of “ Mr. Happy ” or similar products. An initial urine sample, two serial serum samples, and the “ Mr. Happy ” product were tested with liquid chromatographytime-of-fl ight mass spectrometry (LC-TOF/MS) (TOF 6230, LC 1260, Agilent) for 214 pharmaceuticals and drugs of abuse, 40 synthetic cannabinoids and 16 synthetic cathinones, and 3 aminoindanes. Only XLR-11, UR-144, and their common metabolite, XLR-11 Npentanoic acid were identifi ed. Table 1 details the results of the LC-TOF/MS screen. XLR-11 and UR-144 are synthetic cannabinoids that have recently been detected in “ legal high ” products. 3 XLR-11 is the fl uorinated analog of UR-144 and they share a common metabolite, XLR-11 N-pentanoic acid. They are reported to be cannabinoid-2 receptor agonists. 4 There are no reports describing their effects in humans. While multiple adverse effects have been associated with synthetic cannabinoid use, AKI has only been noted in one prior case series. 2 However, that series is limited by the fact that no synthetic cannabinoids were identifi ed in biological or product specimens. While heavy marijuana use has been cited to cause glomerulonephritis, it is unclear how or if XLR-11 or UR-144 are contributing to AKI. 5 The presence of fl uorine in XLR-11 may predispose it or its metabolites to nephrotoxic effects, perhaps similar to fl uorinated anesthetics. 6 It is also possible that this product contained a nephrotoxic plant material or that an unidentifi ed chemical created from the burning of these products may have been responsible. This case report is limited by the fact that these “ legal high ” products are known to vary greatly in their composition over time. 7 Therefore the compounds we identifi ed in this particular “ Mr. Happy ” product and in the patient may differ from those that this patient was exposed to over the past year. Though we have no prior product sample to test, it is likely that the composition or concentration of the synthetic cannabinoids in the “ Mr. Happy ” product evolved over time. This could explain why this patient did not develop AKI earlier despite prolonged use of this product. Furthermore, while we can confi rm recent exposure, we cannot quantify this patient ’ s exposure to this product over the last year. Finally, it remains possible that this patient ’ s AKI and his exposure to XLR-11 and UR-144 are coincidental. This case suggests an association between the use of these synthetic cannabinoids and AKI but further studies examining possible mechanism of injury are needed. Until further information is available, it may be prudent for health care providers to consider AKI as a possible complication from the use of XLR-11 and UR-144.

Comprehensive analysis of “bath salts” purchased from California stores and the internet

Abstract Study objective. To analyze the contents of “bath salt” products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. Methods. A convenience sample of “bath salt” products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. Results. Thirty-five “bath salt” products were purchased and analyzed. Prices ranged from

Simultaneous detection of multiple designer drugs in serum, urine, and CSF in a patient with prolonged psychosis

9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. “bath salt” products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. Conclusion. Comprehensive analysis of “bath salts” purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. “bath salt” products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

False-Positive Urine Phencyclidine Immunoassay Screen Result Caused by Interference by Tramadol and Its Metabolites

This case report is considered exempt from University of California-San Diego Investigational Review Board. Introduction. There is a limited published experience detailing detection and toxicity of multiple novel psychoactive substances. We report a case of a patient with prolonged psychosis who had JWH-072, cannabicyclohexanol, 3’,4’-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and methylenedioxyamphetamine (MDA) identified in multiple biological samples. Case details. An 18-year-old man presented to the emergency department (ED) with acute onset psychosis after allegedly smoking “spice.” Due to agitation and psychosis refractory to multiple medications, a lumbar puncture was performed and he was admitted. All blood, urine, and CSF (cerebral spinal fluid) testing was normal. He remained psychotic for almost 1 week. MDPPP, JWH-072 and MDA were detected in initial blood, urine, and CSF samples. Cannabicyclohexanol was detected only in his serum. Discussion and conclusion. JWH-072 is a cannabinoid-2 receptor (CB-2) agonist which has not been reported previously in the literature. Its clinical effects are unknown. Cannabicyclohexanol is a known component of “spice” products and has been associated with agitation and psychosis. MDPPP and MDA are designer phenylethylamines likely to cause agitation and sympathomimetic symptoms. Simultaneous detection of novel psychoactive substances in multiple biological fluids has not been previously reported. This case suggests that the interaction of these particular substances may be associated with prolonged psychosis.

Castor bean seed ingestions: A state-wide poison control system's experience

Phencyclidine is one of the drugs of abuse included in qualitative urine drug screens that are frequently ordered in the emergency department despite concerns about specificity and clinical utility. Many drugs have been described to cause false-positive results for phencyclidine. We present 2 cases of false-positive phencyclidine qualitative urine drug screen results in patients with seizures from tramadol misuse or abuse. The involvement of tramadol and its active metabolite, N-desmethyltramadol, was confirmed by in vitro testing. These cases illustrate that tramadol and its metabolites can trigger a false-positive phencyclidine urine drug screen result in nonfatal cases and highlight the lack of specificity of the phencyclidine qualitative urine drug screen.

Pediatric zolpidem ingestion demonstrating zero-order kinetics treated with flumazenil.

Abstract Context. Ingestions of the seed of the castor bean plant (Ricinus communis) carries the risk of toxicity from ricin, a potent inhibitor of protein synthesis. Objective. We sought to describe characteristics of castor bean seed exposures reported to a state-wide poison control system. Methods. This was an observational case series. A state-wide poison control systems database was reviewed for exposures to castor bean plant seeds from 2001 to 2011. Case notes were reviewed and data collected, when available, included age, gender, circumstances surrounding exposure, number of castor beans consumed, whether beans were chewed or crushed, symptoms described, laboratory values (aspartate aminotransferase [AST], alanine aminotransferase [ALT], prothrombin time [PT] and international normalized ratio [INR]), duration of follow-up, treatment, and patient outcomes. Results. Eighty-four cases were identified. Ingestions were unintentional in 50 cases (59%) cases and intentional in 34 (40%) cases. A median of 10 seeds (range: 1–20) were ingested in intentional cases versus 1 seed (range: 1–40) in unintentional cases. In 49 (58%) of cases the seeds were reported to have been chewed or crushed. Gastrointestinal symptoms were the most commonly reported symptoms. Vomiting (n = 39), nausea (n = 24), diarrhea (n = 17), and abdominal pain (n = 16) predominated. One patient developed hematochezia and vomiting after reportedly ingesting and intravenously injecting castor bean seeds. Laboratory values were documented in 17 (20%) cases. Only one abnormality was noted; an asymptomatic patient one week following ingestion had AST/ALT of 93 U/L and 164 U/L, respectively. Ricinine was confirmed in the urine of two patients. Twenty-three (27%) cases received activated charcoal. Seventy-two (86%) of cases were calls from health care facilities or referred to health care facilities by the poison control center. Twenty-two (26%) cases were admitted for a median of 2 days (range: 1–10). Admitted cases ingested a median of 8.5 seeds (range: 1–20). Intentional ingestions were followed for median of 37.5 h (range: 0.5–285.5) while unintentional cases were followed for 14 h (range: 1–182). No delayed symptoms, serious outcomes, or deaths were reported. Discussion. Due to the presence of ricin, there is concern for serious outcomes after ingestions of the seeds of the castor bean plant. In this study GI symptoms were most commonly reported but serious morbidity or mortality was not present. The true risk of castor bean plant seed ingestions should continue to be re-evaluated. Conclusion. In this retrospective review, gastrointestinal symptoms were the most common symptoms described after reported exposures to castor bean seeds. These exposures were not associated with serious morbidity, mortality, or delayed symptoms.

Beyond Ketamine and Phencyclidine: Analytically Confirmed Use of Multiple Novel Arylcyclohexylamines

Abstract Zolpidem is a widely prescribed anti-insomnia agent. Although most pediatric zolpidem ingestions are benign, large ingestions can cause significant central nervous system (CNS) depression. Flumazenil has been reported to reverse the CNS effects of zolpidem. We describe a case of a large pediatric zolpidem ingestion resulting in profound CNS depression that responded to flumazenil administration. Serial zolpidem serum levels confirmed the ingestion. A 10-year-old boy with trisomy 21 presented to the emergency department 1 hour after he was found sedate with several zolpidem 5-mg tablets in his mouth. Seventeen tables (85 mg) were unaccounted for from a prescription bottle. He became unarousable approximately 2 hours after his ingestion. Flumazenil 0.2 mg intravenously was given with rapid return to his baseline mental status. He became resedate 1 hour later but was arousable. Sixteen hours after his presentation, he was asymptomatic. Serial zolpidem serum levels were obtained, showed an initial level of 310 ng/mL, and demonstrated zero-order kinetics. Zolpidem is an imidazopyridine, which binds to the benzodiazepine receptor. It is rapidly absorbed and has a short-half life. Unintentional pediatric ingestions of zolpidem are typically well tolerated. However, this case demonstrates that large ingestions may cause significant and prolonged CNS depression. Flumazenil, a benzodiazepine receptor antagonist, has been described to reverse the effects of zolpidem in adult ingestions. There are few published reports describing flumazenil use in pediatric ingestion patients. This case suggests that flumazenil may be an effective treatment for zolpidem-induced CNS depression in the pediatric patient.

Encephalopathy from unintentional donepezil and memantine ingestion.

ABSTRACT Background: Methoxetamine and 3-methoxy-phencyclidine are novel arylcyclohexylamines whose use and clinical toxicity are poorly reported in the medical literature. We report a case of analytically confirmed use of both methoxetamine and 3-methoxy-phencyclidine. Case Report: A 27-year-old male presented 10 hours after insufflating an Internet-obtained powder. He was hypertensive, tachycardic, and demonstrated dissociated affect, a delayed verbal response to questions, ataxia, and vertical nystagmus. A urine drug screen was positive for phencyclidine and 11-nor-delta9-THC-9-carboxylic acid. He was admitted and his mental status and blood pressure normalized eight hours later. Blood samples (0, 2, and 3 hours from arrival) and the powders were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Methoxetamine and 3-methoxy-phencyclidine were detected in all samples (279 ng/ml, 205 ng/ml, and 180 ng/ml for methoxetamine; 167 ng/mL, 131 ng/mL, and 90 ng/ml for 3-methoxy-phencyclidine at 0, 2, and 3 hours, respectively). No phencyclidine or tetrahydrocannabinol was detected. Two powders contained methoxetamine while one contained 3-methoxy-phencyclidine. Conclusion: The literature regarding methoxetamine and 3-methoxy-phencyclidine toxicity is limited. Methoxetamine use is associated with altered mental status, ataxia, and hypertension. Toxicity from 3-methoxy-phencyclidine is poorly described. There is no prior case describing serial qualitative analysis. Health care providers should be aware of the novel arylcyclohexylamines and their toxicity.

Unusually Prolonged Presentation of Designer Drug Encephalopathy Responsive to Steroids.

Donepezil and memantine are commonly prescribed antidementia drugs. There is a paucity of literature concerning pediatric ingestions of these drugs. We describe a case of a 2-year-old child who developed encephalopathy after an unintentional ingestion of donepezil and memantine. A 2-year-old girl was found by her family members agitated and reporting visual hallucinations. In the emergency department, she became sedated and had rightward eye deviation. She was hospitalized and had extensive neurological and infectious disease testing that was unremarkable, except for an electroencephalogram, which showed a nonspecific encephalopathy. She recovered with supportive care for 72 hours. Serum concentrations of donepezil and memantine measured on arrival were 470 ng/mL (therapeutic range, 25-50 ng/mL) and 32 ng/mL (therapeutic range, 70-150 ng/mL), respectively. This case demonstrates that unintentional ingestions of memantine and donepezil can potentially cause significant and prolonged neurological symptoms in pediatric patients.

Do rapid comprehensive urine drug screens change clinical management in children

The availability and use of novel psychoactive substances has risen dramatically over the last decade. The unpredictability of their toxicity constitutes a real challenge. We report a case of an adolescent who developed prolonged encephalopathy after ingesting “Hot Molly,” which was found to contain the novel psychoactive substance, methylenedioxybenzylpiperazine when analyzed by high resolution mass spectrometry assay. This is the first case of human toxicity from methylenedioxybenzylpiperazine ingestion in the medical literature confirmed by body fluid analysis presenting with significant and prolonged encephalopathy. The prolonged course may be due to CYP2D6 inhibition from a combination of the methylenedioxyphenyl moiety and the patient’s ultrarapid metabolizer pharmacokinetics. The response to high dose corticosteroids suggests a possible inflammatory effect that warrants further investigation.