Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature

Armenian, Patil; Darracq, Michael A.; Gevorkyan, Jirair; Clark, Shane; Kaye, Bryan; Brandehoff, Nicklaus

doi:10.1016/j.neuropharm.2017.10.017

Cited by 52 publications

(32 citation statements)

References 47 publications

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“…Despite the low concentrations, severe impairment of the individual was however observed. Similar to the cases observed by Armenian et al, 7 confusion, dilated pupils, slurred speech, and lack of coordination are common signs of AB-PINACA toxicity.…”

Section: Resultssupporting

confidence: 84%

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Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Arbouche

Raul

Garnier

et al. 2019

Drug Testing and Analysis

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Synthetic cannabinoid receptor agonists were first identified in herbal products in 2008 advertised as a legal replacement for cannabis. These herbal incense are usually called “spice” and among these, one product in particular has gained popularity: AB‐PINACA (N‐[(2S)‐1‐Amino‐3‐methyl‐1‐oxobutan‐2‐yl]‐1‐pentyl‐1H‐indazole‐3‐carboxamide). This drug has been discovered to have a stronger binding to human cannabinoid CB1 and CB2 receptors than ∆9‐THC.While some articles have been published regarding the presence of AB‐PINACA in biological fluids such as blood and urine, none reports the presence of AB‐PINACA in hair. We have developed and validated a method for detection of AB‐PINACA in hair using a liquid chromatography−tandem mass spectrometry system and applied it to head and pubic hair obtained in a case of intoxication. The validation procedure demonstrated a limit of detection and a limit of quantification of 0.5 and 1 pg/mg, respectively and acceptable linearity, repeatability, and reproducibility. AB‐PINACA tested positive in the blood (5.7 ng/mL) and less than 1 ng/mL was found in urine. The analysis of the hair specimens resulted in an unusual distribution of the drug between head and pubic hair. AB‐PINACA was identified at a higher concentration in head hair (195 pg/mg) versus in pubic hair (5 pg/mg). The very low concentration of AB‐PINACA in the urine after consumption, due to rapid metabolism, could explain this infrequent distribution, as pubic hair can be contaminated by urine. In any case, it cannot be excluded that the high concentration in head hair may be due to environmental contamination.

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Section: Resultssupporting

confidence: 84%

“…In 2018, Armenian et al reported six cases of suspected intoxication from AB‐PINACA and ADB‐PINACA. AB‐PINACA and its pentanoic acid metabolite were detected using a liquid chromatography−time of flight−mass spectrometry (LC−TOF−MS) in two of their cases.…”

Section: Introductionmentioning

confidence: 99%

Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Arbouche

Raul

Garnier

et al. 2019

Drug Testing and Analysis

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“…9 Recreational use of SCs is reported to cause seizures, 10 an acute toxic symptom seen with increasing prevalence in hospital emergency rooms. 2,[11][12][13] Two recent studies showed that THC and the aminoalkylindoles, JWH-018 and AM-2201, produced seizures in mice. The first showed that seizures, recorded visually and by electroencephalogram (EEG), were induced by THC or JWH-018 and prevented by the CB 1 -selective antagonist, AM-251.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ⁹-Tetrahydrocannabinol

Breivogel

Wells

Jonas

et al. 2020

Cannabis and Cannabinoid Research

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Introduction: Synthetic cannabinoids (SCs) are commonly found in preparations used as recreational drugs. Although severe adverse health effects are not generally associated with cannabis use, a rising number of studies document seizures and even death after SC use. In this study, a mouse model is used to investigate the hypothesis that SCs are more toxic than D 9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis. Materials and Methods: Beginning with the SCs, JWH-073 and AM-2201, dose-response curves were generated to find the dose of each drug that was similarly efficacious to 50 mg/kg THC. Mice were given daily intraperitoneal (IP) injections of vehicle, 50 mg/kg THC, 30 mg/kg JWH-073, or 1 mg/kg AM-2201 until tolerance to the antinociceptive and hypothermic effects was complete, and then were assessed for spontaneous and antagonist-precipitated withdrawal and potential organ damage. No differences in tolerance were noted, but AM-2201 showed more rearing in the spontaneous and antagonist-precipitated withdrawal phases than either vehicle or the other two drug treatments. Histopathological examination of these mice revealed no drug-induced lesions. In a subsequent set of experiments, various doses of THC, methanandamide (mAEA), and of a variety of SCs (HU-210, CP55940, JWH-073, AM-2201, and PB-22) were given IP, and convulsions and change in body temperature were quantified. Discussion: The treatments yielded varying numbers of convulsions and a range of changes in body temperature. JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, mAEA, or cannabidiol (CBD) (the latter two producing none). HU-210, CP55940, JWH-073, and mAEA produced greater hypothermia than THC or CBD. Convulsions and hypothermia induced by several agonists were prevented by pretreatment with a CB 1 antagonist, but not a CB 2 antagonist. Conclusions: In agreement with human studies and case reports, this study found that SCs generally produced more seizures than THC. Of particular significance was the finding that mAEA produced far greater hypothermia than THC (similar to most SCs), but unlike the SCs and THC, produced no seizures.

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“…AB-PINACA [(S)-N1(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carbox-amide] ( Uchiyama et al, 2013 ; Wiley et al, 2015 ), is a popular “second generation” SCB that has been reported to produce dangerous adverse effects in human users ( Thornton et al, 2015 ; Armenian et al, 2017 ). Several SCBs identified in K2 products to date exhibit distinct pharmacodynamic and pharmacokinetic properties relative to Δ 9 -THC that may contribute to the enhanced toxicity of these compounds ( Fantegrossi et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

et al. 2018

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Recreational use of marijuana is associated with few adverse effects, but abuse of synthetic cannabinoids (SCBs) can result in anxiety, psychosis, chest pain, seizures and death. To potentially explain higher toxicity associated with SCB use, we hypothesized that AB-PINACA, a common second generation SCB, exhibits atypical pharmacodynamic properties at CB1 cannabinoid receptors (CB1Rs) and/or a distinct metabolic profile when compared to Δ9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive cannabinoid present in marijuana. Liquid chromatography tandem mass spectrometry (LC/MS) identified AB-PINACA and monohydroxy metabolite(s) as primary phase I metabolites (4OH-AB-PINACA and/or 5OH-AB-PINACA) in human urine and serum obtained from forensic samples. In vitro experiments demonstrated that when compared to Δ9-THC, AB-PINACA exhibits similar affinity for CB1Rs, but greater efficacy for G-protein activation and higher potency for adenylyl cyclase inhibition. Chronic treatment with AB-PINACA also results in greater desensitization of CB1Rs (e.g., tolerance) than Δ9-THC. Importantly, monohydroxy metabolites of AB-PINACA retain affinity and full agonist activity at CB1Rs. Incubation of 4OH-AB-PINACA and 5OH-AB-PINACA with human liver microsomes (HLMs) results in limited glucuronide formation when compared to that of JWH-018-M2, a major monohydroxylated metabolite of the first generation SCB JWH-018. Finally, AB-PINACA and 4OH-AB-PINACA are active in vivo, producing CB1R-mediated hypothermia in mice. Taken collectively, the atypical pharmacodynamic properties of AB-PINACA at CB1Rs relative to Δ9-THC (e.g., higher potency/efficacy and greater production of desensitization), coupled with an unusual metabolic profile (e.g., production of metabolically stable active phase I metabolites) may contribute to the pronounced adverse effects observed with abuse of this SCB compared to marijuana.

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Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature

Cited by 52 publications

References 47 publications

Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ⁹-Tetrahydrocannabinol

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

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Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature

Cited by 52 publications

References 47 publications

Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Testing for AB‐PINACA in human hair: Distribution in head hair versus pubic hair

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol

Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC

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Product

Resources

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Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ⁹-Tetrahydrocannabinol