scholarly journals Analysis of synthetic cannabinoid agonists and their degradation products after combustion in a smoking simulator

2019 ◽  
Vol 11 (24) ◽  
pp. 3101-3107 ◽  
Author(s):  
Husain A. Naqi ◽  
Christopher R. Pudney ◽  
Stephen M. Husbands ◽  
Ian S. Blagbrough

An efficient twin-trap smoking inhalation model that simulates human inhalation has been developed; all six synthetic cannabinoids tested were detected.

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 793
Author(s):  
Emmanouil D. Tsochatzis ◽  
Joao Alberto Lopes ◽  
Margaret V. Holland ◽  
Fabiano Reniero ◽  
Giovanni Palmieri ◽  
...  

The rapid diffusion of new psychoactive substances (NPS) presents unprecedented challenges to both customs authorities and analytical laboratories involved in their detection and characterization. In this study an analytical approach to the identification and structural elucidation of a novel synthetic cannabimimetic, quinolin-8-yl-3-[(4,4-difluoropiperidin-1-yl) sulfonyl]-4-methylbenzoate (2F-QMPSB), detected in seized herbal material, is detailed. An acid precursor 4-methyl-3-(4,4-difluoro-1-piperidinylsulfonyl) benzoic acid (2F-MPSBA), has also been identified in the same seized material. After extraction from the herbal material the synthetic cannabimimetic, also referred to as synthetic cannabinoid receptor agonists or “synthetic cannabinoids”, was characterized using gas chromatography-mass spectrometry (GC-MS), 1H, 13C, 19F and 15N nuclear magnetic resonance (NMR) and high-resolution tandem mass spectrometry (HR-MS/MS) combined with chromatographic separation. A cheminformatics platform was used to manage and interpret the analytical data from these techniques.


2018 ◽  
Vol 64 (6) ◽  
pp. 918-926 ◽  
Author(s):  
Annelies Cannaert ◽  
Jolien Storme ◽  
Cornelius Hess ◽  
Volker Auwärter ◽  
Sarah M R Wille ◽  
...  

Abstract BACKGROUND Synthetic cannabinoids are the largest group of new psychoactive substances monitored by the European Monitoring Centre of Drugs and Drug Addiction. The rapid proliferation of novel analogs makes the detection of these new derivatives challenging and has initiated considerable interest in the development of so-called “untargeted” screening strategies to detect these compounds. METHODS We developed new, stable bioassays in which cannabinoid receptor activation by cannabinoids led to recruitment of truncated β-arrestin 2 (βarr2) to the cannabinoid receptors, resulting in functional complementation of a split luciferase, allowing readout via bioluminescence. Aliquots (500 μL) of authentic serum (n = 45) and plasma (n = 73) samples were used for simple liquid–liquid extraction with hexane:ethyl acetate (99:1 v/v). Following evaporation and reconstitution in 100 μL of Opti-MEM® I/methanol (50/50 v/v), 10 μL of these extracts was analyzed in the bioassays. RESULTS Truncation of βarr2 significantly (for both cannabinoid receptors; P = 0.0034 and 0.0427) improved the analytical sensitivity over the previously published bioassays applied on urine samples. The new bioassays detected cannabinoid receptor activation by authentic serum or plasma extracts, in which synthetic cannabinoids were present at low- or sub-nanogram per milliliter concentration or in which Δ9-tetrahydrocannabinol was present at concentrations >12 ng/mL. For synthetic cannabinoid detection, analytical sensitivity was 82%, with an analytical specificity of 100%. CONCLUSIONS The bioassays have the potential to serve as a first-line screening tool for (synthetic) cannabinoid activity in serum or plasma and may complement conventional analytical assays and/or precede analytical (mass spectrometry based) confirmation.


2017 ◽  
pp. 5-14
Author(s):  
Heather B. Clayton ◽  
Richard Lowry ◽  
Carmen Ashley ◽  
Amy Wolkin ◽  
Althea M. Grant

BACKGROUND AND OBJECTIVES Data are limited on the behavioral risk correlates of synthetic cannabinoid use. The purpose of this study was to compare the behavioral risk correlates of synthetic cannabinoid use with those among marijuana users. METHODS Data from the 2015 Youth Risk Behavior Survey, a cross-sectional survey conducted in a nationally representative sample of students in grades 9 through 12 (N = 15 624), were used to examine the association between self-reported type of marijuana use (ie, never use of marijuana and synthetic cannabinoids, ever use of marijuana only, and ever use of synthetic cannabinoids) and self-report of 36 risk behaviors across 4 domains: substance use, injury/violence, mental health, and sexual health. Multivariable models were used to calculate adjusted prevalence ratios. RESULTS Students who ever used synthetic cannabinoids had a significantly greater likelihood of engaging in each of the behaviors in the substance use and sexual risk domains compared with students who ever used marijuana only. Students who ever used synthetic cannabinoids were more likely than students who ever used marijuana only to have used marijuana before age 13 years, to have used marijuana ≥1 times during the past 30 days, and to have used marijuana ≥20 times during the past 30 days. Several injury/violence behaviors were more prevalent among students who ever used synthetic cannabinoids compared with students who ever used marijuana only. CONCLUSIONS Health professionals and school-based substance use prevention programs should include strategies focused on the prevention of both synthetic cannabinoids and marijuana.


Synthesis ◽  
2018 ◽  
Vol 50 (23) ◽  
pp. 4683-4689 ◽  
Author(s):  
Mark Trudell ◽  
Ryan McKinnie ◽  
Tasneam Darweesh ◽  
Phoebe Zito ◽  
Terrell Shields

An efficient method for the construction of the 5-fluoro-4-hydroxypentyl side chain common to a number of synthetic cannabinoid metabolites was developed. A series of hydroxyl protecting groups was examined to assess the viability as orthogonal protecting groups for epoxidation and regioselective hydrofluorination. The 1-[5-fluoro-4-(diphenyl-tert-butylsilyloxy)]pentyl tosylate was prepared in 67% overall yield (six steps) from pent-4-en-1-ol and was employed for the synthesis of the 4-hydroxy metabolites of the synthetic cannabinoid 5F-APINACA and CUMYL-5F-PINACA.


2019 ◽  
Vol 44 (3) ◽  
pp. 207-217 ◽  
Author(s):  
Alex J Krotulski ◽  
Amanda L A Mohr ◽  
Barry K Logan

Abstract Synthetic cannabinoids pose significant threats to public health and safety, as their implications in overdose and adverse events continue to arise in United States and around the world. Synthetic cannabinoids have seen several generations of chemically diverse structural elements, impacting potency and effects. These factors create new analytical challenges for forensic laboratories. This report describes an efficient liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) assay for the identification of synthetic cannabinoid parent compounds and metabolites, including real-time identification of emergent compounds, using a SCIEX TripleTOF® 5600+ with non-targeted SWATH® acquisition. Method validation evaluated precision/accuracy, limits of detection, interferences, processed sample stability and carryover, for which 19 parent compounds and 19 metabolites were tested. To demonstrate feasibility, de-identified blood sample extracts were acquired from a large forensic toxicology laboratory and analyzed using the validated LC-QTOF-MS assay. In mid-2018, 200 blood extracts were analyzed, demonstrating a 19% positivity rate with > 94% agreement rate with original testing. In addition, three newly discovered synthetic cannabinoids were identified, including 5F-MDMB-PICA, 4-cyano CUMYL-BUTINACA and 5F-EDMB-PINACA. These synthetic cannabinoids were previously unreported in forensic toxicology casework in the United States. 5F-MDMB-PICA has become the most prevalent synthetic cannabinoid in United States, as of early 2019. These results demonstrate the effectiveness of this assay and workflow in the identification and characterization of synthetic cannabinoids, as well as the usefulness of sample-mining using non-targeted mass acquisition by LC-QTOF-MS for the discovery of NPS. High resolution mass spectrometry should be considered when developing new or novel assays for synthetic cannabinoids.


2019 ◽  
Vol 19 (5) ◽  
Author(s):  
Carla Ferreira ◽  
Joana Couceiro ◽  
Carlos Família ◽  
Carolina Jardim ◽  
Pedro Antas ◽  
...  

ABSTRACT Synthetic cannabinoids are a group of novel psychoactive substances with similar properties to Δ9-THC. Among the vast number of synthetic cannabinoids, designed to be tested in clinical trials, JWH-018 was the first novel psychoactive substance found in the recreational drug marketplace. The consumption of JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia and psychotropic effects, but appeared to be more potent than Δ9-THC. However, studies on human cells have shown that JWH-018 toxicity depends on the cellular line used. Despite these studies, the underlying molecular mechanisms to JWH-018 action has not been clarified yet. To understand the impact of JWH-018 at molecular and cellular level, we used Saccharomyces cerevisiae as a model. The results showed an increase in yeast growth rate in the presence of this synthetic cannabinoid due to an enhancement in the glycolytic flux at expense of a decrease in pentose phosphate pathway, judging by 2D-Gel proteomic analysis, qRT-PCR experiments and ATP measurements. Overall, our results provide insights into molecular mechanisms of JWH-018 action, also indicating that Saccharomyces cerevisiae is a good model to study synthetic cannabinoids.


2016 ◽  
Vol 24 (6) ◽  
pp. 598-601 ◽  
Author(s):  
Julie Courts ◽  
Virginia Maskill ◽  
Andrew Gray ◽  
Paul Glue

Aims: Use of synthetic cannabinoids is associated with significant physical and psychological harms. This research quantified reported toxicities from published reports and assessed the influence of size of the reported study population on rates of symptom reporting. Methods: Systematic review of published case reports and case series of toxicity associated with use of synthetic cannabinoids. Results: Symptoms associated with synthetic cannabinoid toxicity were reported for 3695 individuals, predominantly young males. Symptoms included physiological (e.g. tachycardia, hypertension, nausea/vomiting), emotional (e.g. agitation, irritability, paranoia), behavioural (e.g. drowsiness, aggression) and perceptual (e.g. hallucinations) domains. Most common symptoms were tachycardia (30.2% of cases), agitation (13.5%), drowsiness (12.3%), nausea/vomiting (8.2%) and hallucinations (7.6%). Death or serious medical complications were uncommon (e.g. death 0.2%, stroke 0.1%, myocardial infarction 0.09%). Case reports/smaller case series ( n<10) reported statistically significantly higher rates for 29/34 symptoms than larger case series ( n≥10), which could represent selection bias. Conclusions: Symptoms of synthetic cannabinoid toxicity are variable and cover a number of physical and psychological domains. Symptom reporting varies by study population size. Due to the variable presenting symptoms of synthetic cannabinoid toxicity, clinicians in emergency services should consider synthetic cannabinoid toxicity when evaluating young adult male patients presenting with unexplained agitation or cardiovascular symptoms.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Adejare Atanda ◽  
Jessica C. Goodell ◽  
Sherry Adams ◽  
Veronica Black

ObjectiveDevelop a free text query to track synthetic cannabinoid-related ED visits.Assess trends in synthetic cannabinoid use from 2013-2018 using spatial and time-series analysis.IntroductionMaryland utilizes ESSENCE for identification of emerging public health threats, including non-fatal overdoses. Synthetic cannabinoids are heterogeneous psychoactive compounds identified as substances of abuse.[1] In March 2018, the Illinois Department of Public Health received reports of unexplained bleeding in patients who reported using these products.[2] As a result, CDC initiated coordination of national surveillance activities for possible cases of coagulopathy associated with synthetic cannabinoids use. By May 2018, state health departments reported 202 cases, including five deaths. [3]On April 3, 2018, Maryland reported its index case - a female in her 20’s who presented to an ED with nausea, blood in her stool, vaginal bleeding, bruising, an elevated internal normalized ratio (> 12.2), and bleeding oral ulcers after quitting use of a synthetic cannabinoid. She was successfully treated with Vitamin K. The first reported mortality in a Maryland resident was a male in his 30’s who called EMS for fever and blood in his urine but subsequently went into cardiac arrest and was unable to be resuscitated. The patient was known to use synthetic cannabinoids. Brodifacoum exposure was confirmed by laboratory testing. As of September 2018, the Maryland Poison Control Center had received reports of 43 cases, and 3 deaths linked to the outbreak.MethodsTo support surveillance and timeliness of synthetic cannabinoids reporting, we developed a case definition by conducting key word searches to identify terms/phrases used by providers in Maryland ED’s to document synthetic cannabinoid visits. This process yielded the following terms: “synthetic marijuana”, “spice”, and “K2”.Subsequently, we created a free text query based on the case definition and variations of the terms/phrases. This query allowed us to capture data on ED visits for synthetic cannabinoid use in the chief complaint (CC), discharge diagnosis (DD), and clinical impression (CI) fields of ESSENCE data.Finally, descriptive and geographic spatial analyses were conducted of synthetic cannabinoid-related morbidity (ED visits) for 2013-2017 (data for 2018 is incomplete); and time trends analyzed for 2013-2018.ResultsFrom 2013 to 2017, a total of 1,097 ED visits across Maryland were synthetic cannabinoid-related (Table 1). The overall crude synthetic cannabinoid-related ED visit rate was 20 per 100,000 population. The number of synthetic cannabinoid-related ED visits increased 8-fold, from 40 in 2013 to 353 in 2017. Females made the most synthetic cannabinoid-related ED visits (n = 861, 78%). Adults aged 15-24 and 25-34 made 349 (32%) and 367 (33%) visits respectively to an ED for a synthetic cannabinoid-related event. Whites and blacks made 466 (42%) and 498 (45%) visits respectively to an ED for a synthetic cannabinoid-related event. People who were non-Hispanic (n= 988, 90%), black (n = 498, 45%), female (n = 861, 78%), and aged 25-34 (367, 33%) visited an ED for a synthetic cannabinoid-related event more than any other demographic group.Time trend analysis shows an increase from baseline in synthetic cannabinoid-related ED visits starting from July 2014 (Figure 1). Three spikes are noted thereafter in April, July, and September 2015 respectively. Consequently, ED visits for synthetic cannabinoid-related events dropped to a new baseline value in December 2015. Two spikes are also noted for synthetic cannabinoid-related ED visits in May and September 2017 respectively with a new baseline established starting January 2018.Spatial analysis shows geographic clustering of synthetic cannabinoid-related morbidity in three Maryland jurisdictions; Baltimore City, Fredrick County, and Washington County (Figure 2).The top five Maryland counties with crude synthetic cannabinoid-related ED visit rates included Allegany, Baltimore City, Frederick, St. Mary’s and Washington; ranging from 87 in Washington county to 38 in St. Mary’s county. The top ten crude synthetic cannabinoid-related ED visit rates per 100,000 population from 2013 to 2017 among all Maryland ZIP codes ranged from 87 in Washington county to 38 in St. Mary’s county.Spatial analysis also shows that hospitals with the greatest burden of synthetic cannabinoid-related ED visits were close to ZIP codes of communities with high crude synthetic cannabinoid-related ED visit rates (Figure 3).ConclusionsData from the ESSENCE program can be considered acceptable for monitoring synthetic cannabinoid-related ED visits in Maryland. It is useful for obtaining near real-time data about synthetic cannabinoid-related events, and as we have shown in our analysis, for the identification of key groups and geographic locations most in need of targeted interventions to reduce morbidity and mortality. Finally, it also provides us with the ability to retrospectively identify outbreaks, and to link data trends to ongoing interventions.References[1] Riederer, Anne et al. Acute Poisonings from Synthetic Cannabinoids — 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010–2015. Centers for Disease Control and Prevention. MMWR. July 2016. Retrieved from: https://www.cdc.gov/mmwr/volumes/65/wr/mm6527a2.htm[2] Horth, Roberta. Notes from the Field: Outbreak of Severe Illness Linked to the Vitamin K Antagonist Brodifacoum and Use of Synthetic Cannabinoids — Illinois, March–April 2018[3] Centers for Disease Control and Prevention. Outbreak of life-threatening coagulopathy associated with synthetic cannabinoids use. May 2018. Retrieved from: https://emergency.cdc.gov/han/han00410.asp


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