Use and Risk Perception of Electronic Nicotine Delivery Systems and Tobacco in Pregnancy.

INTRODUCTION: Given the rapid rise in availability and use, understanding the perception of electronic nicotine delivery systems (ENDS) products in pregnant women is vital. As more women of reproductive age use these products, it is likely that their use during pregnancy is also increasing. This study investigated the use of ENDS and tobacco cigarettes, along with knowledge and perceptions of associated health risks in pregnant women. METHODS: A cross-sectional survey was conducted at a university-based obstetrical clinic. A 32-item self-administered survey was used to collect participants' knowledge, use, and risk perceptions of ENDS and tobacco smoking. Bivariate associations of demographics and ENDS user status were explored using Chi-square or Fisher's exact tests. Average differences in agreement with perception statements across ENDS user status were tested using ANOVA with Tukey's tests for multiple comparisons. RESULTS: Of 382 participants, 57.9% were 21-29 years old and 60.1% had some college or higher education. 30.3% reported using both ENDS and tobacco cigarettes and 11.9% were current ENDS users. The majority of participants had adequate knowledge about the facts and safety of ENDS and there was no difference across three ENDS user status groups. ENDS users perceived significantly lower risk of ENDS and higher benefit of using ENDS to aid quitting tobacco smoking, compared to non-ENDS users. The majority of participants reported that their healthcare providers less frequently assessed ENDS use during their prenatal visits, compared to tobacco cigarette use. CONCLUSIONS: There is critical need for healthcare providers to increase the screening for ENDS use during pregnancy and promote awareness of risks and benefits of ENDS in pregnant women.

Altered metabolism of synthetic cannabinoid JWH-018 by human cytochrome P450 2C9 and variants.

Synthetic cannabinoids (SCBs), synonymous with 'K2', 'Spice' or 'synthetic marijuana', are psychoactive drugs of abuse that frequently result in clinical effects and toxicity more severe than those classically associated with Δ9-tetrahydrocannabinol such as extreme agitation, hallucinations, supraventricular tachycardia, syncope, and seizures. JWH-018 is one of the earliest compounds identified in various SCB products, and our laboratory previously demonstrated that JWH-018 undergoes extensive metabolism by cytochromes P450 (P450), binds to, and activates cannabinoid receptors (CBRs). The major enzyme involved in the metabolism of JWH-018 is CYP2C9, a highly polymorphic enzyme found largely in the intestines and liver, with *1 being designated as the wild type, and *2 and *3 as the two most common variants. Three different major products have been identified in human urine and plasma: JWH-018 (ω)-OH, JWH-018 (ω-1)-OH(R), and JWH-018 (ω-1)-OH(S). The (ω-1)-OH metabolite of JWH-018 is a chiral molecule, and is thus designated as either (ω-1)-OH(R) or (ω-1)-OH(S). Here, in vitro enzyme kinetic assays performed with human recombinant CYP2C9 variants (*1, *2, and *3) revealed that oxidative metabolism by CYP2C9*3 resulted in significantly less formation of (ω)-OH and (ω-1)-OH metabolites. Surprisingly, CYP2C9*2 was roughly 3.6-fold more efficient as the CYP2C9*1 enzyme based on Vmax/Km, increasing the rate of JWH-018 metabolism and allowed for a much more rapid elimination. These results suggest that genetic polymorphisms of P450 enzymes result in the production of varying levels of biologically active JWH-018 metabolites in some individuals, offering a mechanistic explanation for the diverse clinical toxicity often observed following JWH-018 abuse.

Electronic cigarette use, knowledge, and perceptions among health professional students.

INTRODUCTION: Our study evaluated the electronic cigarette (e-cigarette) use, knowledge, and perceptions of health professional students enrolled in one of five colleges at a single academic health center. METHODS: A 56-item survey was conducted to examine the use, knowledge, and perceptions of e-cigarettes among health professional students. An e-cigarette knowledge score was calculated according to correct responses to eight true-false survey items, with possible scores ranging from zero to eight points. Regressions were used to determine associations between students' enrolled college/discipline and e-cigarette knowledge scores and to identify associations between three perception domains (smoking cessation, harm reduction, and enhanced regulation) and e-cigarette use. RESULTS: Of the 853 students responding, 24.2% reported e-cigarette ever-use. Of e-cigarette ever users, 85.5% had used within the past year, and 23.1% used e-cigarettes for smoking cessation. Participants from the colleges of public health, pharmacy, and nursing had significantly higher knowledge scores, compared to those in allied health. Knowledge scores from college of medicine participants did not differ significantly compared to scores from allied health. Perceptions of using e-cigarettes for smoking cessation, reduced harm compared to tobacco, and reduced e-cigarette regulation were significantly associated with using e-cigarettes. DISCUSSION AND CONCLUSIONS: Self-reported ever-use of e-cigarettes among health professional students in this sample was 3.5-6 times higher than previously reported among medical and nursing students. Substantial gaps in e-cigarette knowledge exist. Enhancing health professionals' preparedness to effectively advise patients about the benefits and harms of e-cigarettes is crucial.

Forensic investigation of K2, Spice, and "bath salt" commercial preparations: a three-year study of new designer drug products containing synthetic cannabinoid, stimulant, and hallucinogenic compounds.

New designer drugs such as K2, Spice, and "bath salts" present a formidable challenge for law enforcement and public health officials. The following report summarizes a three-year study of 1320 law enforcement cases involving over 3000 products described as vegetable material, powders, capsules, tablets, blotter paper, or drug paraphernalia. All items were seized in Arkansas from January 2010 through December 2012 and submitted to the Arkansas State Crime Laboratory for analysis. The geographical distribution of these seizures co-localized in areas with higher population, colleges, and universities. Validated forensic testing procedures confirmed the presence of 26 synthetic cannabinoids, 12 designer stimulants, and 5 hallucinogenic-like drugs regulated by the Synthetic Drug Prevention Act of 2012 and other state statutes. Analysis of paraphernalia suggests that these drugs are commonly used concomitantly with other drugs of abuse including marijuana, MDMA, and methamphetamine. Exact designer drug compositions were unpredictable and often formulated with multiple agents, but overall, the synthetic cannabinoids were significantly more prevalent than all the other designer drugs detected. The synthetic cannabinoids JWH-018, AM2201, JWH-122, JWH-210, and XLR11 were most commonly detected in green vegetable material and powder products. The designer stimulants methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (methylone), and α-methylamino-valerophenone (pentedrone) were commonly detected in tablets, capsules, and powders. Hallucinogenic drugs were rarely detected, but generally found on blotter paper products. Emerging designer drug products remain a significant problem and continued surveillance is needed to protect public health.

Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology.

Designer synthetic cannabinoids like JWH-018 and AM2201 have unique clinical toxicity. Cytochrome-P450-mediated metabolism of each leads to the generation of pharmacologically active (ω)- and (ω-1)-monohydroxyl metabolites that retain high affinity for cannabinoid type-1 receptors, exhibit Δ(9)-THC-like effects in rodents, and are conjugated with glucuronic acid prior to excretion in human urine. Previous studies have not measured the contribution of the specific (ω-1)-monohydroxyl enantiomers in human metabolism and toxicity. This study uses a chiral liquid chromatography-tandem mass spectroscopy approach (LC-MS/MS) to quantify each specific enantiomer and other nonchiral, human metabolites of JWH-018 and AM2201 in human urine. The accuracy (average % RE = 18.6) and reproducibility (average CV = 15.8%) of the method resulted in low-level quantification (average LLQ = 0.99 ng/mL) of each metabolite. Comparisons with a previously validated nonchiral method showed strong correlation between the two approaches (average r(2) = 0.89). Pilot data from human urine samples demonstrate enantiospecific excretion patterns. The (S)-isomer of the JWH-018-(ω-1)-monohydroxyl metabolite was predominantly excreted (>87%) in human urine as the glucuronic acid conjugate, whereas the relative abundance of the corresponding AM2201-(ω-1)-metabolite was low (<5%) and did not demonstrate enantiospecificity (approximate 50:50 ratio of each enantiomer). The new chiral method provides a comprehensive, targeted metabolomic approach for studying the human metabolism of JWH-018 and AM2201. Preliminary evaluations of specific enantiomeric contributions support the use of this approach in future studies designed to understand the pharmacokinetic properties of JWH-018 and/or AM2201.

K2 toxicity: fatal case of psychiatric complications following AM2201 exposure.

Limited forensic and clinical experience and the lack of confirmatory testing strategies for synthetic cannabinoids (SC) prevent adequate characterization of SC toxicity and the potential impact on public health. A statewide surveillance system identified a fatality involving a 23-year-old man found with a large stab wound to the neck following use of a SC product suspected of containing AM2201. Analytical testing for common SCs, SC metabolites, routine drugs of abuse, and over-the-counter medications was performed on heart blood obtained at autopsy. Additionally, assays were performed on the SC raw material and drug paraphernalia found on the decedent. High concentrations of AM2201 were detected in all samples. AM2201 metabolites were detected in postmortem blood. Other than a trace amount of JWH-073 found in smoke residue, no other substances were detected. Psychiatric complications including self-induced, lethal trauma can occur after the use of SC products.

Comparison of the effects of energy drink versus caffeine supplementation on indices of 24-hour ambulatory blood pressure.

BACKGROUND: Cardiovascular events associated with energy drink consumption have been reported, but few data exist to delineate the hemodynamic effects of energy drinks. OBJECTIVE: To compare the effects of an energy drink versus caffeine supplementation on blood pressure (BP) indices as measured by 24-hour ambulatory BP monitoring (ABPM). METHODS: Healthy, nonsmoking, normotensive volunteers (aged 18-45 years) taking no medications were enrolled in a single-center, open-label, 2-period crossover pilot study. During each study period, subjects received either an energy drink (Red Bull Energy Drink, each dose containing 80 mg of caffeine and 1000 mg of taurine in an 8.3-oz serving) or a control (compounded caffeine solution, each dose containing 80 mg of caffeine solution in 8 oz of bottled water) at 0800, 1100, 1500, and 1900 hours and underwent 24-hour ABPM. The study periods were separated by a washout period (4-30 days). Mean 24-hour, daytime, and nighttime systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP; BP load; and percent nocturnal dipping were compared between study periods. RESULTS: Nine subjects (5 females, mean [SD] age 27.7 [5.0] years) completed the study. Mean 24-hour SBP (123.2 vs 117.4 mm Hg, p = 0.04), DBP (73.6 vs 68.2 mm Hg, p = 0.02), and MAP (90.1 vs 84.8 mm Hg, p = 0.03) were significantly higher during energy drink supplementation versus caffeine supplementation. Daytime DBP (77.0 vs 72.0 mm Hg, p = 0.04) also was significantly higher with the energy drink versus caffeine supplementation. Trends in higher daytime SBP (127.0 vs 121.9 mm Hg, p = 0.05) and MAP (93.6 vs 88.6 mm Hg, p = 0.05) were recorded with energy drink supplementation versus caffeine supplementation. Nighttime SBP and DBP loads were significantly higher with the energy drink, but nocturnal dipping did not differ significantly between study periods. CONCLUSIONS: Single-day energy drink supplementation increased mean 24-hour and daytime BP compared to caffeine control in this pilot study. Additional research is warranted to better understand the hemodynamic effects of energy drink consumption.

Evaluation of centrally acting cholinesterase inhibitor exposures in adults.

BACKGROUND: There are 4 centrally acting cholinesterase inhibitors (CA-ChEI) available in the US: tacrine, galantamine, rivastigmine, and donepezil. Documented clinical experience involving exposure to these agents is limited. The lack of information makes decisions involving excessive or unintended CA-ChEI exposure difficult. OBJECTIVE: To assess the effects, demographics, and outcomes of CA-ChEI exposures reported to US poison centers. METHODS: A retrospective review of the Toxic Exposure Surveillance System of the American Association of Poison Control Centers data of acute and acute-onchronic exposures involving only a CA-ChEI in patients 19 years of age or older with documented medical outcomes from 2000-2005 was performed. RESULTS: There were 1026 records that met criteria for this study. Patients aged 70-89 years made up 73% of reports; 69% of the patients were female. Moderate (197) and major outcomes (20) accounted for 21% of exposures. There were no deaths. Clinical effects that occurred in 5% or more of patients included vomiting (34%), nausea (28%), diarrhea (12%), dizziness/vertigo (9.9%), drowsiness/lethargy (7.7%), diaphoresis (7.4%), tremor (5.2%), and bradycardia (5%). Patients were admitted to the hospital in 19% of all exposures. Of those patients, 42% were admitted to a critical care unit. The majority (65%) of exposures were attributed to unintentional therapeutic error. Patients received at least one form of therapy in 47% of exposures, including intravenous fluid (111), antiemetic (48), atropine (17), benzodiazepine (15), oxygen (14), antihypertensive (4), pralidoxime (4), intubation (3), antihistamine (2), antiarrhythmic (1), anticonvulsant (1), and pacemaker (1). CONCLUSIONS: The majority of patients evaluated in this retrospective study experienced no or mild effect; however, significant or life-threatening effects were observed in a small group of patients and an appreciable number of patients were admitted to a healthcare facility.