• Novel Psychoactive Substances: Analytical Approaches, Military Prevalence, and Human Metabolite Profiling

      Castaneto, Marisol S.; Huestis, Marilyn; Squibb, Katherine S.; 0000-0003-4426-6663 (2015)
      The rapid and ongoing emergence of novel psychoactive substances poses a serious public health and safety threat. We investigated how clinical and forensic toxicology laboratories can best address novel psychoactive substances proliferation. We performed a comprehensive literature review of 913 articles to identify knowledge gaps in the pharmacodynamics, pharmacokinetics, epidemiology, chemistry, toxicity, and detection of synthetic cannabinoids. Synthetic cannabinoids provided users an alternative to achieve cannabis' effects and avoid detection in routine drug tests, making synthetic cannabinoids intake attractive to individuals subject to drug testing including athletes, police, commercial drivers, and military personnel. We analyzed 20,017 randomly collected urine specimens from US service members stationed around the world for synthetic cannabinoids and piperazines with a biochip array technology immunoassay. We identified 1432 synthetic cannabinoids and 840 piperazines presumptive-positive specimens. After confirmation of presumptive-positive and randomly selected presumptive-negative specimens by liquid chromatography tandem mass spectrometry (LC-MS/MS) or LC-high-resolution MS (LC-HRMS), we obtained a 1.4% synthetic cannabinoids positivity rate. In addition, 0.4% specimens confirmed for designer piperazines, the majority positive (N=72) for 1-(3-chlorophenyl)piperazine (mCPP) and trazodone, an antidepressant metabolizing to mCPP and prescribed to treat insomnia and/or post-traumatic stress disorder. We also optimized immunoassay performance for four synthetic cannabinoids and three designer piperazines urine drug screening methods. Our AB-FUBINACA metabolic stability and metabolite profile studies with human liver microsomes and human hepatocytes incubation and LC-HRMS identified AB-FUBINACA as a low-clearance drug (extraction ratio =0.34) with a window of detection in urine of a few days. Of 11 metabolites identified in human hepatocytes, AB-FUBINACA carboxylic acid was the most dominant metabolite generated by amide hydrolysis. Metabolites also were verified in authentic urine specimens. We present here best approaches for novel psychoactive substances identification in urine for clinical and forensic drug testing programs, and analytical methods for determining metabolic stability and profiles with human liver microsomes, human hepatocytes, and HRMS. Identifying specific synthetic cannabinoid intake is critical for tying the drug to adverse events and educating the public on the drugs' danger.
    • Synthetic cannabinoid use and clinical correlates among youth in treatment for substance use disorders

      Selby, Victoria Lynn; Storr, Carla L. (2017)
      Statement of the problem: Little is known about synthetic cannabinoids (SC) use among adolescents and young adults admitted to residential substance use treatment programs. The purpose of this study is to explore the extent of SC use in this population, identify characteristics of those at greatest risk to use, and examine psychiatric comorbidities, as well as associated risk behavior unique to SC users that may complicate treatment and recovery. Methods: This is a case-control study using retrospective chart review of patients, ages 12-25. SC users (n = 227) were compared to a random sample of nonusers (n = 202). Relationships between SC use (lifetime, recency, and amount of use) and characteristics, psychiatric indicators, and risk behaviors were examined using chi-square comparisons and logistic regression models. Results: Nearly one-third (32.5%) of the youth entering treatment had lifetime SC use. SC use was more common among males (OR=1.64, CI=1.02, 2.63, p=0.04), Whites (OR=1.94, CI =1.18, 3.20, p=0.009), and LGBT identifying youth (OR=2.19, 95%, CI =1.06, 4.52, p=0.04); while it was less common among those preferring opioids (OR=0.49, CI=0.30, 0.80, p=0.004). Persistent use was more common than experimental use in youth with legal involvement (OR=2.17, CI=1.12, 4.27, p=0.02) and having two or more choice drugs (OR=2.80, CI=1.45, 5.42, p=0.002). Youth who reported lifetime SC use had over three times the odds of having a diagnosis of psychotic disorder (OR=3.38, CI=1.89, 9.61, p=0.02). Amount of use and recency of use was not significantly associated with psychotic disorders. Lifetime SC users were more likely to be prescribed an antipsychotic medication (OR=1.89, 95%, CI=1.18, 3.05, p=0.01). Lifetime hallucinogen use was a behavior associated with lifetime SC use (OR=1.68, 95%, CI=1.08, 2.62, p=0.03). Conclusions: SC use was fairly common among these patients. Recognizing personal characteristics and risk behaviors that are associated with SC use may help health care providers to recognize users and those at risk of using; however, it is important to screen all patients. Prevention strategies for youth are needed, especially for those with legal involvement and who identify as LGBT. Psychiatric morbidity such as psychosis is associated with SC, which may complicate treatment.