Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2013–2016: A Review

Abstract

Novel psychoactive substances (NPS) represent significant analytical and interpretive challenges to forensic and clinical toxicologists. Timely access to case reports and reports of adverse incidents of impairment or toxicity is imperative to clinical diagnosis and treatment, as well as to interpretation of forensic results. Delays in identifying the presence of a novel intoxicating agent have significant consequences for public health and public safety. Adverse effects of intoxications with novel cannabinoids, stimulants, hallucinogens, benzodiazepines and opioids spanning January 2013 through December 2016 as reported in emergency departments, death investigations, impaired driving cases and other forensic contexts are the subject of this review. Discussion of the chemistry, pharmacology and adverse events associated with novel drug classes is summarized and described within. Adverse effects or symptoms associated with ingestion of more than 45 NPS have been abstracted and summarized in tables, including demographics, case history, clinical or behavioral symptoms, autopsy findings and drug confirmations with quantitative results when provided. Based on these findings and gaps in the available data, we provide recommendations for future toxicological testing of these evolving substances. These include development and management of a national monitoring program to provide real-time clinical and toxicological data, confirmed analytically, on emerging drugs and their known toxidromes and side effect profiles. Increased efforts should be made to analytically confirm the agents responsible for clinical intoxications involving adverse events in emergency department admissions or hospitalizations. Evidence-based community preparedness among analytical laboratories gained through active communication and sharing of toxicological findings and trends in NPS is imperative to assist in enabling early detection of new drugs in forensic and clinical populations.

Designer Benzodiazepines: A Review of Published Data and Public Health Significance

“…7,14 Norflurazepam, also named desalkykflurazepam, is the principal active metabolite of flurazepam, 10,17,18 a BZ hypnotic used in the United States since 1970. 6,[28][29][30][31] In cases of overdose, some designer BZs can be detected with adequate sensitivity by immunoassay-based urine drug screening. 10,21 The principal determinants of elimination 10 This scenario is not difficult to envision if a user is not familiar with a particular compound, or ingests an impure mixture of multiple compounds.…”

Analysis of fentanyl analogs and novel synthetic opioids in blood, serum/plasma, and urine in forensic casework

“…In 2015, the fentanyl analogs acetylfentanyl and butyrylfentanyl were ranked the 10th and 12th most frequently identified drugs respectively when looking specifically at narcotic analgesics. 12 Between 2012 and 2016, 17 fentanyl analogs were reported to the United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory, some of which include para-methoxybutyrylfentanyl, acetylfentanyl, acrylfentanyl, beta-hydroxythiofentanyl, butyrylfentanyl, and valerylfentanyl. 19 Additionally, in the NFLIS brief on fentanyl and fentanyl-related substances at least 10 compounds including 2-furanylfentanyl, carfentanil, 3-methylfentanyl, and valerylfentanyl appeared for the first time in 2016.…”

“…8 Although there have been reports of overdose deaths caused by these fentanyl analogs, 3,[9][10][11][12][13][14][15][16][17] it is suspected that synthetic-opioid-related deaths are underestimated since many laboratories do not test for fentanyl or related analogs, and others lack the appropriate sensitivity for some of these highly potent emerging agents. 8 Although there have been reports of overdose deaths caused by these fentanyl analogs, 3,[9][10][11][12][13][14][15][16][17] it is suspected that synthetic-opioid-related deaths are underestimated since many laboratories do not test for fentanyl or related analogs, and others lack the appropriate sensitivity for some of these highly potent emerging agents.…”

Detection of the designer benzodiazepine flunitrazolam in urine and preliminary data on its metabolism

“…New psychoactive substances (NPS) are comprised of various narcotic or psychotropic drugs (i) that are not controlled by the 1961 United Nations Single Convention on Narcotic Drugs or the 1971 United Nations Convention on Psychotropic Substances, and (ii) that usually (but not exclusively) replicate chemical structures and/or pharmacological effects of controlled substance groups, such as opiates, ecstasy, amphetamine, cocaine or cannabis. Currently, NPS represent a significant analytical and interpretative challenge for forensic and clinical toxicologists . The online availability of NPS on specialized websites has rapidly increased over the last decade.…”