Motor vehicle collisions caused by the ‘super-strength’ synthetic cannabinoids, MAM-2201, 5F-PB-22, 5F-AB-PINACA, 5F-AMB and 5F-ADB in Japan experienced from 2012 to 2014

Abstract

From 2012 to 2014 in Japan, 214 cases of motor vehicle collisions were attributed to the use of illegal drugs. In 93 out of 96 investigated cases, the causative agents were a variety of synthetic cannabinoids (SCs). These SCs can be classified into three groups according to the lineage of the chemical structures: (1) naphthoyl indoles, such as MAM-2201, (2) quinolinyl ester indoles, such as 5F-PB-22, and (3) indazole carboxamides, such as 5F-AB-PINACA, 5F-AMB, and 5F-ADB. These SCs became available sequentially with increasing cannabinoid CB1 agonist potencies and reached a nationwide outbreak in the summer of 2014. They caused acute intoxication with impaired consciousness, anterograde amnesia (impaired memory), catalepsy with muscle rigidity, tachycardia, and vomiting or drooling soon after smoking. Drivers who had abused one of these SCs might unexpectedly experience the acute intoxication that caused uncontrolled driving. These SCs were generally difficult to detect from body fluid samples. It is thought that the highly lipophilic SCs disappear from the blood via rapid degradation by liver enzymes and selective accumulation into adipose tissues. Thus, much effort should be directed to the development of fast and sensitive chemical detection of the drug usage.

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

“…One of the earliest reports of 5F-ADB identified in non-biological (botanical) and biological samples (fluids and tissues) was based on the autopsy laboratory results published by Hasegawa et al after a nationwide outbreak of multiple synthetic cannabinoids in Japan in 2014. 26,27 According to annual reports by the DEA Special Testing and Research Laboratory, between 2016 and 2017, 5F-ADB was one of the most-detected synthetic cannabinoids (top 3) in the United States, and the most prevalent in 2018-2019, totaling approximately 500 cases for all years combined. 10,[28][29][30] DEA 2018 data are consistent with reports by The Center for Forensic Science Research and Education's NPS Discovery program, highlighting 5F-ADB as one of the most prevalent compounds in circulation.…”

Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids

“…A major cause of concern is that some of the more recently seen synthetic cannabinoids are more likely to produce extremely toxic effects than the older synthetics (Tai and Fantegrossi, 2017). Waves of emergency room visits with severe adverse effects including death have been related to the introduction of particular compounds to geographical area s (Davidson et al, 2017; Weinstein et al, 2017), such that these compounds have been referred to as “super-strength” (Kaneko, 2017). It is not known whether the increased toxicity is due only to activation of CB 1 cannabinoid receptors more strongly than Δ 9 -THC or whether these “super-strength” cannabinoids produce effects at other receptors.…”

“…5F-MDMB-PINACA has been associated with reports of intoxication (Barceló et al, 2017), increased rates of traffic accidents (Kaneko, 2017) and fatalities (Angerer et al, 2017; Kusano et al, 2018). MDMB-CHIMICA intoxication resulted in numerous adverse effects including acidosis, reduced level of consciousness or agitation, mydriasis, tachycardia or bradycardia, and tonic-clonic convulsions, with recovery occurring within 24 h (Hill et al 2016).…”

Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

“…Though these interesting data prompted us to further investigate their effects upon chronic use, the toxicological study of these rimonabant/Fubinaca hybrids should be a primary issue. Documented side effects of Fubinaca series compounds are impaired driving, acute psychiatric distress, aggressiveness and polysubstance abuse with several SCs and alcohol [59,60,61,62,63,64]. These effects are also correlated to populations’ changes in consuming SCs, such as incarcerated persons, homeless, and their cultural heritage [65,66,67].…”