Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity.

AKB48 and its fluorinated derivative 5F-AKB48 are synthetic cannabinoids (SCs) which have caused hospitalizations and deaths in human users. Abuse of SCs is dangerous because users may mistake them for natural cannabis, which is generally considered to be unlikely to elicit adverse effects. The present studies were designed to investigate the in vitro oxidative metabolism of 5F-AKB48 by human microsomal fractions from different organs and sexes as well as recombinant human cytochrome P450s (P450s).

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 Δ-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.

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.

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.

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.

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.

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.

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.