Characteristics of novel psychoactive substance exposures reported to New York City Poison Center, 2011-2014.

BACKGROUND: Novel psychoactive substances (NPS) are emerging at an unprecedented rate. Likewise, prevalence of use and poisonings has increased in recent years. OBJECTIVE: To compare characteristics of NPS exposures and non-NPS-drug-related exposures and to examine whether there are differences between exposures involving synthetic cannabinoid receptor agonists (SCRAs) and other NPS. METHODS: Poison control center data from the five counties of New York City and Long Island were examined from 2011-2014. We examined prevalence and characteristics of NPS exposures (classified as intentional abuse) and compared characteristics of cases involving SCRAs and other NPS. RESULTS: Prevalence of NPS exposures was 7.1% in 2011, rising to 12.6% in 2014. Most exposures (82.3%) involved SCRA use. The second and third most prevalent classes were phenethylamines/synthetic cathinones ("bath salts"; 10.2%) and psychedelic phenethylamines (4.3%). Compared to other drug-related exposures (i.e. involving licit and illicit drugs), those who used NPS were more likely to be younger, male, and to have not co-used other drugs (ps < 0.001). SCRA exposures increased sharply in 2014 and the mean age of users increased over time (p < 0.01). Females exposed to SCRAs were younger than males (p < 0.001), and in 2014, individuals exposed to SCRAs were more likely to report concomitant use of alcohol than users of other NPS (p = 0.010). Users of other NPS were more likely than SCRA users to report concomitant use of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)/"Molly" (p < 0.001). CONCLUSION: Exposures reported to the poison center that involve NPS are increasing and the majority involve SCRAs. These findings should inform prevention and harm reduction approaches.

["Spice"--synthetic cannabinoids with dangerous effects]. / ¼Spice« - syntetiska kannabinoider med riskabla effekter - Fall av akut njursvikt och cerebral ischemi med stroke har rapporterats.

Synthetic cannabinoids are a large group of chemicals functionally related to delta-9-tetrahydrocannabinol (THC) found in Cannabis sativa. These compounds are full agonists on cannabinoid receptors, therefore more potent than THC. Products marketed over the Internet intended for abuse usually consist of dried inert plant material sprayed with different kinds of cannabinoids. Smoking is the most common route of administration. In Sweden commercially available products are usually labeled ¼spice«. A case concerning a young male with convulsions and acute kidney failure requiring temporary dialysis is presented. Other reported serious effects of this group of substances are acute psychosis, unconsciousness, cardiac ischemia, seizures and stroke. The vendors are very aware of the legal situation in each country and adjust their supply according to current narcotics classifications. New, previously unknown cannabinoids are constantly appearing on the market.

Evolution of clinical characteristics and outcomes of synthetic cannabinoid receptor agonist exposure in the United States: analysis of National Poison Data System data from 2010 to 2015.

BACKGROUND AND AIMS: New synthetic cannabinoid receptor agonists (SCRAs) are synthesized each year to evade US governmental regulation and sold for recreational use. Our aim was to estimate the changes in the clinical effects and patient disposition associated with SCRA exposure from 2010 to 2015. DESIGN: A retrospective observational cohort study. SETTING: National Poison Data System that collects data on reports of poisonings from US poison centers. PARTICIPANTS: A total of 19 388 isolated SCRA cases between 1 January 2010 and 31 December 2015 were identified. The mean age was 24.6 years and 77.8% were male. MEASUREMENTS: Primary outcome was the change in the trend of patient disposition, i.e. treated and released versus hospitalization (e.g. non-critical care, critical care unit or psychiatry) between 2010 and 2015. Secondary outcomes included the trends in the clinical effects and their duration, and therapeutic interventions nationally and regionally. FINDINGS: Reports of SCRA exposure peaked in 2011 (n = 5305) and 2015 (n = 5475). The majority of patients required supportive care and were treated and released from an emergency department. Hospitalization increased by annual percentage change in the log odds (APCO) of 21.0% (P < 0.0001) during the 6 years, with significant increases in admissions to critical care units and non-critical care units. Overall, tachycardia (32.1%), agitation/irritation (25.6%) and drowsiness/lethargy (20.4%) were the most frequently reported clinical effects from SCRA exposure. Clinical effects resolved within 2-8 hours in 52.8% of cases, but their duration increased markedly by 2015. Regionally, the largest number of SCRA cases was reported in the South (n = 9374, 48.6%). SCRA cases in the Northeast were hospitalized more frequently (27.4%), with cases in the Midwest being admitted more frequently to critical care units (15.3%). However, there were no significant differences in clinical toxicity or disposition among the regions. CONCLUSION: Hospitalization resulting from toxicity from synthetic cannabinoid receptor agonists exposure in the United States increased significantly between 2010 and 2015.

Antidote to cannabinoid intoxication: the CB1 receptor inverse agonist, AM251, reverses hypothermic effects of the CB1 receptor agonist, CB-13, in mice.

BACKGROUND AND PURPOSE: Cannabis is a recreational drug leading to intoxication, following stimulation of cannabinoid CB1 receptors. However, more recently, herbs mixed with synthetic cannabinoids sometimes known as 'Spice' and 'Black Mamba' have been increasingly used, and their high CB1 receptor affinity has led not only to marked intoxication but also life-threatening complications and an increasing number of deaths. Although many studies have indicated that prophylactic treatment with CB1 receptor antagonists can block cannabimimetic effects in animals and humans, the aim of this study was to determine whether CB1 receptor antagonism could reverse physical cannabimimetic effects. EXPERIMENTAL APPROACH: Cannabimimetic effects, measured by the hypothermic response following sedation and hypomotility, were induced by the synthetic CB1 receptor agonist CB-13 (1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone) in Biozzi Antibody High mice. The CB1 receptor antagonist/inverse agonist AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) was administered 20 min after the injection of CB-13 and its effects on the cannabimimetic responses were assessed. KEY RESULTS: In this study, the CNS-related cannabimimetic effects, as measured by the hypothermic effect, induced by the CB1 receptor agonist were therapeutically treated and were rapidly reversed by the CB1 receptor antagonist/inverse agonist. There was also a subjective reversal of visually evident sedation. CONCLUSIONS AND IMPLICATIONS: Cannabinoid receptor antagonists have been widely used and so may provide an acceptable single-dose antidote to cannabinoid intoxication. This use may save human life, where the life-threatening effects are mediated by cannabinoid receptors and not off-target influences of the synthetic cannabinoids or non-cannabinoids within the recreational drug mixture.

The impact of Australian legislative changes on synthetic cannabinoid exposures reported to the New South Wales Poisons Information Centre.

BACKGROUND: The emergence of new psychoactive substances (NPS), including synthetic cannabinoid receptor agonists (SCRAs) poses novel challenges for drug regulation and public health. Misconceptions of safety and legality, coupled with the fact that NPS are undetectable on routine drugs screens contributes to their popularity. Concerns over the unpredictable toxicity and abuse potential of NPS has led to a variety of legislative responses worldwide. We wish to describe Australian trends in SCRA use, examining the effects of legislative changes on calls to Australia's largest poisons centre. METHODS: A retrospective review of calls to the New South Wales Poisons Information Centre (NSWPIC). Cases occurring between 1 January 2010 and 30 June 2015 with documented use of SCRAs were included. RESULTS: There were 146 exposures to SCRAs recorded in the NSWPIC database. Federal bans of specific SCRA compounds in 2011/2012 had little impact on call volumes. State-based legislation introduced in 2013 banning specific brand names of SCRA products was followed by a dramatic, sustained decrease in exposures. The most common symptoms reported with SCRA use were tachycardia, vomiting, drowsiness, anxiety/panic, decreased level of consciousness, chest pain, agitation, hallucinations, confusion, seizures and hypertension. CONCLUSION: Banning of specific brand names of SCRA (timed with raids and social media campaigns) appears effective at reducing SCRA exposures. We postulate that this raised awareness within the community of the illegality of these substances while also reducing supply through bricks-and-mortar shops. These results could help inform future legislative responses.

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA.

CONTEXT: MDMB-CHMICA is a synthetic cannabinoid receptor agonist which has caused concern due to its presence in cases of adverse reaction and death. METHOD: 43 cases of suspected synthetic cannabinoid ingestion were identified from patients presenting at an Emergency Department and from post-mortem casework. These were subjected to liquid-liquid extraction using tertiary-butyl methyl ether and quantitatively analysed by Electrospray Ionisation Liquid Chromatography-tandem Mass Spectrometry. For positive samples, case and clinical details were sought and interrogated. RESULTS: 11 samples were found positive for MDMB-CHMICA. Concentrations found ranged from <1 to 22 ng/mL (mean: 6 ng/mL, median: 3 ng/mL). The age range was 15-44 years (mean: 26 years, median: 21 years), with the majority (82%) of positive results found in males. Clinical presentations included hypothermia, hypoglycaemia, syncope, recurrent vomiting, altered mental state and serotonin toxicity, with corresponding concentrations of MDMB-CHMICA as low as <1 ng/mL. Duration of hospitalisation ranged from 3 to 24 h (mean: 12 h, median: 8 h). DISCUSSION: The concentration range presented in this case series is indicative of MDMB-CHMICA having a high potency, as is known to be the case for other synthetic cannabinoid receptor agonists. The age range and gender representation were consistent with that reported for users of other drugs of this type. The clinical presentations observed were typical of synthetic cannabinoid receptor agonists and show the difficulties in identifying reactions potentially associated with drugs of this type. CONCLUSION: The range of MDMB-CHMICA concentrations in Emergency Department presentations (n = 9) and post-mortem cases (n = 2) was reported. No correlation between the concentration of this drug and clinical presentation or cause of death was reported in this sample. However, the potential for harm associated with low concentrations of MDMB-CHMICA and the symptoms of toxicity being non-specific were highlighted.

Acute intoxication of four individuals following use of the synthetic cannabinoid MAB-CHMINACA.

CONTEXT: The largest group of new psychoactive substances (NPS) are synthetic cannabinoids (SC). Those that become controlled are immediately replaced by new uncontrolled substances. The recent resurgence of the NPS market in Poland resulted in a further amendment to the Drug Addiction Counteraction Act. This resulted in significant changes in the composition of "legal high" preparations, and consequently a large outbreak of intoxications with SC was reported in Poland at the beginning of July 2015. CASE DETAILS: This paper describes the circumstances of intoxication and toxicological findings in an acute intoxication of four individuals with MAB-CHMINACA. They each smoked tobacco mixed with powder from the package with the description "AM-2201". The adverse effects observed in the individuals included vomiting, seizures, limb twisting, muscle tremors, aggression, agitation, slurred speech, blood pressure spikes, wheezing, respiratory failure and losses of consciousness. Blood samples were analysed using liquid chromatography with mass spectrometry. Results from analysis performed on the blood samples showed the presence of MAB-CHMINACA, while AM-2201 was not found (LOD 0.09 ng/mL). The determined concentrations were 5.2, 1.3, 1.7 and 14.6 ng/mL, respectively. The analyses of the blood did not reveal any other substances (excluding medicines given in hospital). CONCLUSION: The presented cases show the health risks associated with MAB-CHMINACA use and confirm that "legal high" preparations do not always contain a substance represented on the package.

Case Series of Synthetic Cannabinoid Intoxication from One Toxicology Center.

Synthetic cannabinoid use has risen at alarming rates. This case series describes 11 patients exposed to the synthetic cannabinoid, MAB-CHMINACA who presented to an emergency department with life-threatening toxicity including obtundation, severe agitation, seizures and death. All patients required sedatives for agitation, nine required endotracheal intubation, three experienced seizures, and one developed hyperthermia. One developed anoxic brain injury, rhabdomyolysis and died. A significant number were pediatric patients. The mainstay of treatment was aggressive sedation and respiratory support. Synthetic cannabinoids pose a major public health risk. Emergency physicians must be aware of their clinical presentation, diagnosis and treatment.

Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation.

INTRODUCTION: Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance. CASE REPORT: We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of "cannabis tea" and "mushroom tea") as well as two LSD blotters. After the "cannabis tea" was smoked and the two LSD blotters and "mushroom tea" were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20-30 beats) 1-2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression. DISCUSSION: To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.

Using poisons information service data to assess the acute harms associated with novel psychoactive substances.

Novel psychoactive substances (NPS) can cause significant acute toxicity but usually little is known about their toxicity when they enter the recreational drug scene. Current data sources include online user forums, user questionnaires, case reports/series, and deaths; however, these are limited by their focus on sub-populations and generally include severe cases and specific geographical areas. Approximately 54% of countries have at least one poisons information service (in 2012 there were 274 worldwide) providing advice to healthcare professionals and/or the public on poisoning. They provide advice on recreational drug and NPS toxicity. In 2012, 2.5% of telephone enquiries to the UK National Poisons Information Service and 2.4% of enquiries to US poisons centres related to recreational drugs. Data are collected at population level and can be used to complement other data sources with clinical details on acute NPS toxicity and geographical/time patterns of toxicity. Like other acute NPS toxicity data, poisons centre data should be interpreted within their limitations, notably the absence of analytical confirmation and reliance on secondary reporting of clinical features. This manuscript demonstrates the breadth and depth of poisons information service data in the literature with a focus on mephedrone and synthetic cannabinoid-receptor agonists. In our opinion it would be possible to develop a more robust and systematic reporting system using a network of poisons information services both within and across countries that would be complimentary to other datasets on acute NPS toxicity and allow more accurate data triangulation.