An outbreak of synthetic cannabinoid exposures reported to a regional poison center: “K2” identified as 5F-ADB

Arens, Ann M.; Olives, Travis D.; Simpson, Nicholas S; Laes, JoaAn R; Anderson, Deborah; Bangh, Stacey A.; Lee, Samantha C.; Martin, Spencer; Banister, Samuel D.; Gerona, Roy; Cole, Jon B.

doi:10.1080/15563650.2018.1497170

Cited by 9 publications

(6 citation statements)

References 5 publications

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“…Media reports also emphasize the increasing scale of this crisis: more than 25 people were killed and 700 hospitalized in a mass overdose involving the SCRA MDMB-FUBINACA in Russia in 2014 . Outbreaks of 5F-ADB toxicity (with fatalities) have been reported in Minneapolis, MN and Japan (among other locations). A mass-intoxication in New York in 2016, reported at the time as a “zombie outbreak”, was attributed to AMB-FUBINACA, and a string of at least 45 deaths in New Zealand in 2017 was attributed to SCRAs, again predominantly AMB-FUBINACA, , a drug now seemingly implicated in fatalities globally .…”

Section: Introductionmentioning

confidence: 99%

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Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA

Finlay

Manning

Ibsen

et al. 2019

ACS Chem. Neurosci.

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Recreational consumption of synthetic cannabinoid receptor agonists (SCRAs) is a growing crisis in public health in many parts of the world. AMB-FUBINACA is a member of this class of drugs and is responsible for a large proportion of SCRA-related toxicity both in New Zealand and internationally. Strikingly, little is currently known about the mechanisms by which SCRAs exert toxic effects or whether their activity through the CB 1 cannabinoid receptor (the mediator of cannabinoid-related psychoactivity) is sufficient to explain clinical observations. The current study therefore set out to perform a basic molecular pharmacology characterization of AMB-FUBINACA (in comparison to traditional research cannabinoids CP55,940, WIN55,212-2, and Δ 9 -THC) in fundamental pathways of receptor activity, including cAMP inhibition, pERK activation, ability to drive CB 1 internalization, and ability to induce translocation of β-arrestins-1 and -2. Activity pathways were then compared by operational analysis to indicate whether AMB-FUBINACA may be a biased ligand. Results revealed that AMB-FUBINACA is highly efficacious and potent in all pathways assayed. However, surprisingly, bias analysis suggested that Δ 9 -THC, not AMB-FUBINACA, may be a biased ligand, with it being less active in both arrestin pathways than predicted by the activity of the other ligands tested. These data may help predict molecular characteristics of SCRAs. However, more research is required to determine whether these molecular effects manifest in toxicity at tissue/system level.

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Section: Introductionmentioning

confidence: 99%

“…5 Media reports also emphasize the increasing scale of this crisis: more than 25 people were killed and 700 hospitalized in a mass overdose involving the SCRA MDMB-FUBINACA in Russia in 2014. 6 Outbreaks of 5F-ADB toxicity (with fatalities) have been reported in Minneapolis, MN 7 and Japan 8…”

Section: ■ Introductionmentioning

confidence: 99%

Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA

Finlay

Manning

Ibsen

et al. 2019

ACS Chem. Neurosci.

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“…First, it involves data collection in a nonblinded manner. Second, “before–after” designs are far more subject to secular trends, such as the sudden introduction of an abusable novel psychoactive substance in a community, that may disproportionately affect one arm in an adverse manner. Third, while the research activities (observational data collection) are minimal risk, the design of alternating clinical protocols offers no additional protections to the subjects compared to a blinded, randomized trial such as those conducted under EFIC, as in both approaches the patient receives a medication per protocol rather than by physician decision, although the protocol can be overridden in both designs.…”

Section: Discussionmentioning

confidence: 99%

Study Enrollment When “Preconsent” Is Utilized for a Randomized Clinical Trial of Two Treatments for Acute Agitation in the Emergency Department

Cole

Klein

Mullinax

et al. 2019

Academic Emergency Medicine

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Background: Acute agitation in the emergency department (ED) represents a danger to both patients and their caregivers. Medication is often needed, and few high-quality randomized trials have evaluated the optimal drugs for this vulnerable population. In the United States, as of 2017, randomized trials of drugs typically cannot be conducted under Waiver of Consent (46 CFR 45.116), and Exception From Informed Consent trials (21 CFR 50.24) are limited to life-threatening conditions, are onerous, and require filing an investigational new drug application with the FDA. We sought to conduct a randomized double-dummy trial of inhaled loxapine versus intramuscular haloperidol + lorazepam for acute agitation in the ED by obtaining consent in advance ("preconsent") in patients at risk of future agitation, allowing study drug administration up to 3 years later if the patient presented with acute agitation.Objective: We sought to report the successful enrollment rate of patients preconsented at an earlier ED visit for this trial.Methods: This was an analysis of patients age 18 to 64 with bipolar I disorder or schizophrenia preconsented for enrollment in the trial (clinicaltrials.gov, NCT02877108) conducted at a single urban academic center seeing approximately 60,000 patients per year. Eligible patients were assessed for capacity to consent by trained research associates, and informed consent was obtained at an ED visit for the possibility of administering drugs for agitation within the next 3 years. In the event the patient later presented to the ED and the attending physician deemed the patient required treatment for acute agitation, preconsent was confirmed and study drug would be administered.Results: Over 67 days, 1,461 patients were screened in the ED, 269 had bipolar I or schizophrenia, 194 of whom had a contraindication to inhaled loxapine leaving 75 eligible patients; preconsent was obtained in 43 patients. Four additional patients who had not preconsented were consented for the trial in real time (three by surrogate, one patient had capacity while agitated) resulting in a total of 47 consented patients. Of these 47, a total of 12 were later removed from the study: 10 patients had unrecognized exclusion criteria for inhaled

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“…An important limitation of these data, because of their age, is that they were collected before the emergence of novel psychoactive substances, such as “K2,” “spice,” and “bath salts.” 56,57 Furthermore, the incidence of methamphetamine intoxication has increased since the time of the trial 58 . As such, our results may not apply to agitated patients intoxicated on these substances and may alter the medications needed to best treat the resulting agitation.…”

Section: Limitationsmentioning

confidence: 98%

Randomized Double‐blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department

Martel

Miner

Biros

et al. 2020

Academic Emergency Medicine

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Background The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED. Methods This was a randomized, double‐blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end‐tidal carbon dioxide (ETCO2), and pulse oximetry (SpO2) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO2 consistent with respiratory depression or SpO2 < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes. Results We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups. Conclusions Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.

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An outbreak of synthetic cannabinoid exposures reported to a regional poison center: “K2” identified as 5F-ADB

Cited by 9 publications

References 5 publications

Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA

Do Toxic Synthetic Cannabinoid Receptor Agonists Have Signature in Vitro Activity Profiles? A Case Study of AMB-FUBINACA

Study Enrollment When “Preconsent” Is Utilized for a Randomized Clinical Trial of Two Treatments for Acute Agitation in the Emergency Department

Randomized Double‐blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department

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