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A large number of new psychoactive substances are available at the illicit drug market and the synthetic cannabinoids (SCs) are among the substances that have led to serious side effects and death. Knowledge about common concentrations of these drugs are however sparse. Concentrations of APINACA and 5F-APINACA in biological matrixes have previously not been reported, and concentrations of UR-144 and its degradant product in blood samples from driving under the influence of drug (DUID) cases have not been published. The aims of this study were to report concentrations of APINACA, 5F-APINACA, UR-144 and UR-144 degradant from DUID cases analyzed at the Norwegian Institute of Public Health (NIPH), and also previously unpublished concentrations of AM-2201 in cases from our Institute. We have further summarized all the former published studies where concentrations of SCs have been reported, to compare with the results from these newer SCs. In whole blood from one driver we have found 5F-APINACA and from three drivers both APINACA and 5F-APINACA in concentrations from 0.24 to 24.5 and 0.9 to 6.5 μg/L, respectively, and UR-144 in two cases in concentrations of 0.22 and 0.47 μg/L. UR-144 degradant in a concentration of 0.15 μg/L was found in one of the cases. A summary of the literature reveals major deficiencies regarding concentrations of most of the SCs. The SCs most frequently detected in DUID cases were (n≥8) AM-2201, JWH-122, JWH-018 and JWH-210. In intoxication cases AM-2201 (n=517) was the most often detected SC, followed by JWH-122, JWH-210, UR-144, JWH-018, and MAM-2201 (n>100). Four studies regarding concentrations in autopsy cases have been published, and concentrations of four different SCs have been reported (JWH-018, JWH-073, JWH-210, AM-2201 and the metabolites of AM-2201; 4-OH-pentyl, JWH-018 5-OH-pentyl and JWH-018 pentanoic acid). Pharmacokinetic data are only available for JWH-018 (n=3), JWH-073 (n=1) and the metabolites of AM-2201; 4-OH-pentyl, 6-OH-indole, JWH-018 5-OH-pentyl and JWH-018 pentanoic acid (n=1).

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many herbal blends, resinous samples and powders seized from the Polish drug market since the beginning of 2012. This paper presents the case of intoxication by this substance. A complete picture of the symptoms observed by a witness, paramedics and medical doctors are given. In the analysis of powder residues from the plastic bag seized from the intoxicated person by gas chromatography-mass spectrometry (GC-MS), UR-144 and its major pyrolysis product [1-(1-pentyl-1H-indol-3-yl)-3-methyl-2-(propan-2-yl)but-3-en-1-one] were detected. Both substances were also identified in a blood sample collected on admission of the patient to hospital using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS). Blood concentration of UR-144 was 6.1 ng/mL. A urine sample collected at the same time was analyzed by liquid chromatography-quadruple time-of-flight tandem mass spectrometry (LC-QTOF-MS). The parent substance and its pyrolysis products were not detected in urine, while their five metabolites were found. The experiments allowed the location of derivative groups to be established, and thus elucidate rough structures of the metabolites; a dihydroxylated metabolite of UR-144 and mono-, dihydroxylated and carboxylated metabolites of its pyrolysis product were identified.

UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone] is a synthetic cannabinoid, which has been detected in many 'legal highs', seized from the global drug market since the beginning of 2012. It has gained popularity as a 'legal' alternative to classic cannabis in countries where it was not controlled. Despite the widespread distribution of this substance, the data on its effects on the human body are scarce. Therefore, this paper describes the results of analysis and observed effects in 39 cases in which UR-144 was determined in blood. Symptoms were noted from the blood sampling forms filled out by the representative doctor. The determined concentrations of UR-144 were in the range of trace amounts (LOD-0.15ng/mL; LOQ-0.5ng/mL) up to 17ng/mL. The most common observed effects included slurred speech, dilated pupils, sluggish and abnormal pupillary reaction, cheerful behaviour, poor coordination, and staggering. Less frequently observed were: verbosity, narrow pupils, loss of consciousness, pale or reddened facial skin, blackout, euphoria, agitation, hallucinations, hindered communication, shaking hands, seizures, convulsions, somnolence, delayed movements, redness of the conjunctiva, and tachycardia. The discussed cases show the effects observed after UR-144 use. This study can assist in the recognition of possible effects caused by this substance.