Synthetic cathinone poisoning from ingestion of drug-laced "instant coffee packets" in Taiwan.

BACKGROUND: Synthetic cathinone abuse is a global health issue. Synthetic cathinones emerged in Taiwan in 2009, and their prevalence rapidly rose. They are usually made into "instant coffee packets," and these so-called "toxic coffee packets" may also contain psychoactive drugs other than synthetic cathinones. Due to the diversity of the ingredients, clinical presentations can be complex. METHODS: Retrospective analysis of emergency department (ED) patients who reported ingesting toxic coffee packets at three Chang-Gung Memorial Hospitals located in northern Taiwan between January, 2015 and December, 2019. RESULTS: Sixty patients were included. Their mean age was 28.85 ± 9.24 years and 47(78.33%) were male. The most common presentations were palpitation, agitation, hallucination, and altered consciousness. Tachycardia and hypertension were common, while hyperthermia was observed in only three patients. Three patients (5%) developed rhabdomyolysis, and one underwent transient hemodialysis. Most patients were discharged from the ED, but 15(25%) were admitted, of whom nine (15%) were admitted to the intensive care unit (ICU), and one eventually died. Confirmation tests (mass-spectrometry-based analysis) were available in 10 patients; all reported positive for at least one type of synthetic cathinone. Polysubstance exposure was common. In multivariate logistic regression analyses, Glasgow coma scale ≤13 and the presence of seizure were associated with ICU admission. CONCLUSION: Patients who report ingesting toxic coffee packets are very likely to have been exposed to synthetic cathinones. Polysubstance exposure is common following ingestion. Cardiovascular and neurological symptoms are the main presentations, and severe complications such as rhabdomyolysis and life-threatening dysrhythmia can occur.

Intoxication by a synthetic cannabinoid (JWH-018) causes cognitive and psychomotor impairment in recreational cannabis users.

BACKGROUND: Smoking mixtures containing synthetic cannabinoids (SCs) have become very popular over the last years but pose a serious risk for public health. Limited knowledge is, however, available regarding the acute effects of SCs on cognition and psychomotor performance. Earlier we demonstrated signs of impairment in healthy volunteers after administering one of the first SCs, JWH-018, even though subjective intoxication was low. In the current study, we aimed to investigate the acute effects of JWH-018 on several cognitive and psychomotor tasks in participants who are demonstrating representative levels of acute intoxication. METHODS: 24 healthy cannabis-experienced participants took part in this placebo-controlled, cross-over study. Participants inhaled the vapor of 75 µg JWH-018/kg body weight and were given a booster dose if needed to induce a minimum level of subjective high. They were subsequently monitored for 4 h, during which psychomotor and cognitive performance, vital signs, and subjective experience were measured, and serum concentrations were determined. RESULTS: Maximum subjective high (average 64%) was reached 30 min after administration of JWH-018, while the maximum blood concentration was shown after 5 min (8 ng/mL). JWH-018 impaired motor coordination (CTT), attention (DAT and SST), memory (SMT), it lowered speed-accuracy efficiency (MFFT) and slowed down response speed (DAT). CONCLUSION: In accordance with our previous studies, we demonstrated acute psychomotor and cognitive effects of a relatively low dose of JWH-018.

Eutylone Intoxications-An Emerging Synthetic Stimulant in Forensic Investigations.

Synthetic stimulants are the largest class of novel psychoactive substances identified each year by forensic laboratories internationally. While hundreds of these drugs appear in drug powders, only a few proliferate in use among forensically relevant populations and eventually emerge in postmortem and clinical investigations. Beta-keto-methylenedioxyamphetamines (i.e., novel psychoactive substances with names ending in "ylone") are currently the most popular subclass of synthetic stimulants. Leading up to its federal scheduling in 2018, N-ethyl pentylone was the most encountered synthetic stimulant. The popularity of N-ethyl pentylone declined once it was scheduled, but it was quickly replaced by eutylone (bk-EBDB), a structurally related analog from the same family. In cases encountered between January 2019 and April 2020, eutylone was quantitatively confirmed in 83 forensic investigations, including postmortem cases and driving under the influence of drugs cases. Matrix types included blood, urine and tissue. Eutylone was identified in cases submitted from 13 states, demonstrating proliferation around the United States; Florida accounted for 60% of the positive cases. The mean concentration of eutylone in postmortem blood was 1,020 ng/mL (standard deviation = ±2,242 ng/mL; median = 110 ng/mL, range = 1.2-11,000 ng/mL, n = 67). The mean concentration of eutylone in blood from driving under the influence of drugs cases was 942 ng/mL (standard deviation = ±1,407 ng/mL; median = 140 ng/mL, range = 17-3,600 ng/mL, n = 7). This report includes cause and manner of death data for 22 postmortem cases. Further analysis of authentic human specimens revealed the presence of three eutylone metabolites, including one unique biomarker and one metabolite in common with butylone. Laboratories should be aware that eutylone may be present in cases of suspected Ecstasy, "Molly" and/or methylenedioxymethamphetamine use, causing or contributing to impairment or death.

Differences in Opioid Overdose Mortality Rates Among Middle-Aged Adults by Race/Ethnicity and Sex, 1999-2018.

OBJECTIVES: The types of opioids abused in the United States have changed from prescription opioids to heroin to fentanyl. However, the types of opioids abused may differ by demographic factors, especially among middle-aged adults. We examined national trends in opioid overdose mortality rates among middle-aged adults by race/ethnicity and sex. METHODS: Using 1999-2018 data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database, we examined overdose mortality rates per 100 000 population in 2018 among adults aged 45-64 that involved natural and semisynthetic opioids, heroin, synthetic opioids (excluding methadone), and methadone. We tested for significant differences in mortality rates by race/ethnicity and sex. We plotted drug-specific trends by race/ethnicity and sex from 1999 to 2018. RESULTS: In 2018, non-Hispanic White adults had the highest rates per 100 000 population of natural and semisynthetic overdose mortality (men: 8.7; women: 7.9; P < .001), and non-Hispanic Black adults had the highest rates of heroin (men: 17.7; women: 5.4; P < .001) and synthetic opioid (men: 36.0; women: 11.2; P < .001) overdose mortality. Men had significantly higher overdose mortality rates than women did for deaths involving natural and semisynthetic opioids, heroin, and synthetic opioids, but not methadone. From 1999 to 2018, mortality rates increased sharply for heroin and synthetic opioids, increased modestly for natural and semisynthetic opioids, and decreased for methadone. The greatest increases were among non-Hispanic Black men for heroin overdose (3.3 in 1999 to 17.7 in 2018) and synthetic opioid overdose (0.1 in 1999 to 36.0 in 2018). CONCLUSIONS: Policy making should consider unique subgroup risks and alternative trajectories of opioid use other than people being prescribed opioids, developing opioid use disorder, subsequently moving to heroin, and then to fentanyl.

Persistence and Pervasiveness : Early Wave Opioid Overdose Death Rates Associated With Subsequent Overdose Death Rates.

OBJECTIVES: Although trends in opioid-related death rates in the United States have been described, the association between state-level opioid overdose death rates in early waves and substance-related overdose death rates in later waves has not been characterized. We examined the relationship between state-level opioid overdose death rates at the beginning of the crisis (1999-2004) and overdose death rates for opioids and other substances in later years. METHODS: Using 1999-2018 multiple cause of death data from the Centers for Disease Control and Prevention, we first categorized each state by quartile of baseline (1999-2004) opioid overdose death rates. By baseline opioid overdose death rates, we then compared states' annual overdose death rates from any opioid, heroin, synthetic opioids, sedatives, stimulants/methamphetamine, and cocaine from 2005 through 2018. To test the association between baseline opioid overdose death rates and subsequent substance-related overdose death rates for all 6 substances, we estimated unadjusted and adjusted linear models controlling for annual state-level unemployment, median household income, age, sex, and race/ethnicity. RESULTS: Our results suggest 2 characteristics of the opioid crisis: persistence and pervasiveness. In adjusted analyses, we found that for each additional opioid overdose death per 100 000 population at baseline, states had 23.5 more opioid deaths, 4.4 more heroin deaths, 8.0 more synthetic opioid deaths, 9.2 more sedative deaths, 3.3 more stimulant deaths, and 4.6 more cocaine deaths per 100 000 population from 2005 to 2018. CONCLUSION: These findings have important implications for continued surveillance to assist policy makers in deciding how to deploy resources to combat not just opioid use disorder but also polysubstance use disorder and broader problems of substance use disorder.

Uses, Effects and Toxicity of Synthetic Cannabinoids from the Perspective of People with Lived Experiences.

Synthetic cannabinoids (SCs) are a class of synthetic chemicals with cannabis-like properties, and little is known about their pharmacological and toxicological effects. The objective of this study was to explore the effects of SCs and the underlying motivations of use among participants with lived experiences. Content analysis of experiences of people using SCs was carried out based on online discussions. A total of 1660 posts from 50 threads between 2004 and 2016 were examined. Relevant information was recorded on characteristics of users as well as on characteristics of SCs, the modality of their use, and the SC-related experienced effects and toxicity. Users exchanged online significant information on SCs consumption. While a growing amount of attention has been given to the chemical and pharmacological profile of SCs, very little is known about the subjective components of such use. It remains important to study the lived experiences of people who used novel psychoactive substances (NPSs) to implement prevention and treatment, and to guide future research in the field.

Acute and repeated administration of MDPV increases aggressive behavior in mice: forensic implications.

MDPV is a synthetic cathinone illegally marketed and consumed for its psychostimulant effects, which are similar to those produced by cocaine, amphetamines, and MDMA. Clinical reports indicate that MDPV produces euphoria, increases alertness, and at high doses causes agitation, psychosis, tachycardia and hypertension, hallucinations, delirium, hyperthermia, rhabdomyolysis, and even death. In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, demonstrating greater potency than cocaine. Nevertheless, its role in aggressive behavior has been reported but not yet experimentally confirmed. Therefore, the aim of this study was to evaluate the effects of acute and repeated MDPV (0.01-10 mg/kg i.p.) administration on aggressive behavior in mice and to compare them with those of cocaine (0.01-10 mg/kg i.p.) administration. To this purpose, the resident-intruder test in isolated mice and the spontaneous and stimulated aggressiveness tests for group-housed mice were employed. The present study shows for the first time that MDPV enhances aggressive behavior and locomotion in mice with greater potency and efficacy than cocaine treatment. Moreover, the aggressive and locomotor responses are enhanced after repeated administration, indicating that a sensitization mechanism comes into play. These results, although from preclinical investigation, are suggestive that human MDPV intake could be a problem for public health and the criminal justice system. Thus, investigation by police officers and medical staff is needed to prevent interpersonal violence induced by the consumption of synthetic cathinones.

Severe illness associated with reported use of synthetic cannabinoids: a public health investigation (Mississippi, 2015).

STUDY OBJECTIVES: In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC. METHODS: A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). RESULTS: Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05). CONCLUSION: SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

Synthetic cannabinoid "Black Mamba" infidelity in patients presenting for emergency stabilization in Colorado: a P SCAN Cohort.

BACKGROUND: Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. "Black Mamba", often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death. OBJECTIVES: We aim to identify the chemical constituents and quantification of eight cases of reported "Black Mamba" use in order to further understand the clinical variability in patients presenting for emergency stabilization. METHODS: We report data from eight cases of reported "Black Mamba" use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds. RESULTS: In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations. CONCLUSIONS: The wide range of clinical presentations from "Black Mamba" use may be explained by the wide variability of chemical constituents found by laboratory analysis.