The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitragynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol, added. O-Desmethyltramadol is an active metabolite of tramadol, a commonly prescribed analgesic.We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. Neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 µg/g, and O-desmethyltramadol concentrations, determined by gas chromatography with nitrogen-specific detection, ranged from 0.4 to 4.3 µg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.

In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties. This paper presents toxicological findings of synthetic cannabinoids in whole blood from some cases of severe intoxication including quantitative data from recreational users and a fatal intoxication. Samples were analyzed by liquid chromatography–tandem mass spectrometry in a scheduled multiple reaction mode after a basic liquid extraction. Twenty-nine synthetic cannabinoids were included in the method. In our data set of ∼3000 cases, 28% were found positive for one or more synthetic cannabinoid(s). The most common finding was AM-2201. Most of the analytes had median concentrations of <0.5 ng/g in agreement with other published data. The emerging drugs MAM-2201 (n = 151) and UR-144 (n = 181) had mean (median) concentrations of 1.04 (0.37) and 1.26 (0.34), respectively. The toxicity of the synthetic cannabinoids seems to be worse than that of natural cannabis, probably owing to the higher potency and perhaps also to the presence of several different cannabinoids in the smoked incense and the difficulties of proper dosing. The acute toxic effects may under certain circumstances contribute to death.

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB‐BUTINACA (N‐[1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]‐1‐butyl‐1H‐indazole‐3‐carbox‐amide). ADB‐BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB‐BUTINACA was detected in SCRA‐infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA‐infused papers tested between January and July 2021. In this work, ADB‐BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono‐hydroxylation on the n‐butyl tail) and B16 (mono‐hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB‐4en‐PINACA (N‐[1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]‐1‐[pent‐4‐en‐1‐yl]‐1H‐indazole‐3‐carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB‐BUTINACA, prevalence has remained low. ADB‐4en‐PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB‐BUTINACA (EC₅₀, 11.5 nM and ADB‐4en‐PINACA (EC₅₀, 11.6 nM) are similar to that of MDMB‐4en‐PINACA (EC₅₀, 4.3 nM). A third tert‐leucinamide SCRA, ADB‐HEXINACA was also detected in prison samples and warrants further investigation.