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

Kasper, Amelia M.; Ridpath, Alison; Gerona, Roy; Cox, Robert D.; Galli, Robert; Kyle, Patrick B.; Parker, Christina; Arnold, Justin K.; Chatham‐Stephens, Kevin; Morrison, Melissa; Olayinka, Olaniyi; Preacely, Nykiconia; Kieszak, Stephanie; Martin, Colleen; Schier, Joshua G.; Wolkin, Amy; Byers, Paul; Dobbs, Thomas

doi:10.1080/15563650.2018.1485927

Cited by 20 publications

(14 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was initially claimed that SCRAs could be "safe" alternatives to marijuana, due to similarities of their pharmacological profile to D9-THC and other phytocannabinoids, and lots of compounds binding to the cannabinoid receptors have been synthesized and evaluated regarding their binding affinities and activity in animal or cell models since then (6). However, a huge number of in-vitro and in-vivo studies, reports, and alerts have highlighted severe adverse events and enhanced toxicity (2,7,8) prompting the United States Drug Enforcement Administration to classify some of these compounds as Schedule I substances. Signs and symptoms of SCRAs consumption include psychomotor agitation, euphoria, anxiety, confusion, and psychosis on the one side, sedation and loss of consciousness on the other (9,10).…”

Section: Introductionmentioning

confidence: 99%

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

et al. 2020

View full text Add to dashboard Cite

Background: Synthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities, and mechanisms as well as toxic/lethal doses are still scarce. Methods: A comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included. Results: Of 380 studies identified, 354 were excluded, while 8 additional manuscripts were included through the screening of relevant references cited in the selected articles. A total number of 34 manuscripts (8 case series and 26 case reports) were included. Conclusions: Typical toxic ranges for SCRAs have not been so far identified, and the results of toxicological analyses should be interpreted with caution. In death cases involving SCRAs, a thorough post-mortem examination is a prerequisite to assess the role of the substance use in the deceased and to identify a probable mechanism of death. Even after a comprehensive analysis of clinical, circumstantial, toxicological, and autoptic data, the cause and manner of death remain unclear in some cases.

show abstract

Section: Introductionmentioning

confidence: 99%

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Even for the most well‐studied SCRA NPS, existing data pertain to the activity of these compounds in cellular systems or animal models, with very few human studies reported . Of greater concern is the trend for increasing potency of SCRA NPS, with the most recent examples frequently associated with serious adverse effects, including myocardial infarction, ischemic stroke, acute kidney injury, tonic–clonic convulsion, coma, and death …”

Section: Introductionmentioning

confidence: 99%

“…22 Of greater concern is the trend for increasing potency of SCRA NPS, with the most recent examples frequently associated with serious adverse effects, including myocardial infarction, ischemic stroke, acute kidney injury, tonic-clonic convulsion, coma, and death. [23][24][25][26][27][28][29][30][31][32] The largest class of SCRA NPS are 1-substituted indole-and indazole-3-carboxamides. These typically feature secondary amides, as found in 2 and 3, however, tertiary amides comprised of alicyclic or heterocyclic substituents have occasionally been reported.…”

mentioning

confidence: 99%

The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F‐PY‐PICA, 5F‐PY‐PINACA, and their analogs

Banister

Kevin

Martin

et al. 2019

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

5F‐PY‐PICA and 5F‐PY‐PINACA are pyrrolidinyl 1‐(5‐fluoropentyl)ind (az)ole‐3‐carboxamides identified in 2015 as putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS). 5F‐PY‐PICA, 5F‐PY‐PINACA, and analogs featuring variation of the 1‐alkyl substituent or contraction, expansion, or scission of the pyrrolidine ring were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–quadrupole time‐of‐flight–mass spectrometry (LC–QTOF–MS). In competitive binding experiments against HEK293 cells expressing human cannabinoid receptor type 1 (hCB1) or type 2 (hCB2), all analogs showed minimal affinity for CB1 (pKi < 5), although several demonstrated moderate CB2 binding (pKi 5.45–6.99). In fluorescence‐based membrane potential assays using AtT20‐hCB1 or ‐hCB2 cells, none of the compounds (at 10 μM) produced an effect >50% of the classical cannabinoid agonist CP55,940 (at 1 μM) at hCB1, although several showed slightly higher relative efficacy at hCB2. Expansion of the pyrrolidine ring of 5F‐PY‐PICA to an azepane (8) conferred the greatest hCB2 affinity (pKi 6.99) and activity (pEC50 7.54, Emax 72%) within the series. Unlike other SCRA NPS evaluated in vivo using radio biotelemetry, 5F‐PY‐PICA and 5F‐PY‐PINACA did not produce cannabimimetic effects (hypothermia, bradycardia) in mice at doses up to 10 mg/kg.

show abstract

“…To date, these drugs were predominately offered as herbal blends (e.g., ‘Spice’, ‘K2’) with the compounds being sprayed onto dried plant material [ 1 – 3 ]. In contrast to cannabis, intoxications with synthetic cannabinoids can lead to life-threatening conditions [ 4 – 6 ] and the number of patients who were delivered to emergency rooms after consumption of synthetic cannabinoids increased during the last years [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

5F-Cumyl-PINACA in ‘e-liquids’ for electronic cigarettes: comprehensive characterization of a new type of synthetic cannabinoid in a trendy product including investigations on the in vitro and in vivo phase I metabolism of 5F-Cumyl-PINACA and its non-fluorinated analog Cumyl-PINACA

et al. 2018

View full text Add to dashboard Cite

PurposeIn recent years e-liquids used in electronic cigarettes have become an attractive alternative to smoking tobacco. A new trend is the use of e-liquids containing synthetic cannabinoids (SCs) instead of smoking cannabis or herbal mixtures laced with SCs. In the frame of a systematic monitoring of the online market of ‘legal high’ products, e-liquids from online retailers who also sell herbal blends were bought.MethodsThe products were analyzed by gas chromatography-mass spectrometry. In some of the e-liquids an unknown compound was detected which was identified as the SC 5F-Cumyl-PINACA (1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide) by nuclear magnetic resonance analysis. To investigate the phase I metabolism of this new class of compounds, 5F-Cumyl-PINACA and its non-fluorinated analog Cumyl-PINACA were incubated with pooled human liver microsomes (pHLM). Cumyl-PINACA was additionally ingested orally (0.6 mg) by a volunteer in a controlled self-experiment. To assess the relative potency of Cumyl-PINACA a set of SCs were characterized using a cAMP assay.ResultsMetabolism of 5F-Cumyl-PINACA and Cumyl-PINACA showed similarities with AM-2201 and JWH-018. The main metabolites were formed by hydroxylation at the N-pentyl side chain. The main metabolites detected in the volunteer’s urine sample were the same as in the pHLM assay. All SCs tested with the cAMP assay were full agonists at the CB1 receptor. Cumyl-PINACA was the most potent SC among the tested compounds and showed an EC50 value of 0.06 nM.ConclusionsThe increasing popularity of e-liquids particularly among young people, and the extreme potency of the added SCs, pose a serious threat to public health. To our knowledge, this is the first report describing the tentative identification of human in vivo metabolites of Cumyl-PINACA and 5F-Cumyl-PINACA.Electronic supplementary materialThe online version of this article (10.1007/s11419-018-0451-8) contains supplementary material, which is available to authorized users.

show abstract

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

Abstract: 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.

Cited by 20 publications

References 15 publications

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F‐PY‐PICA, 5F‐PY‐PINACA, and their analogs

5F-Cumyl-PINACA in ‘e-liquids’ for electronic cigarettes: comprehensive characterization of a new type of synthetic cannabinoid in a trendy product including investigations on the in vitro and in vivo phase I metabolism of 5F-Cumyl-PINACA and its non-fluorinated analog Cumyl-PINACA

Contact Info

Product

Resources

About