Extensive phytocannabinoid profiles of seized cannabis and cannabis-based medicines - Identification of potential distinguishing markers.

As the frequency of cannabis-based therapy increases, the ability to distinguish intake of cannabis-based medicines from recreational cannabis use becomes desirable. Minor cannabinoids have been suggested to indicate recreational cannabis use in biological matrices but are unreliable when presumably also present in directly plantderived medicines. Thus, for therapeutics such as medical cannabis, Sativex® and Dronabinol, a more thorough investigation of cannabinoid profiles is required to identify possible distinguishing markers. In this study, 16 phytocannabinoids were quantified in samples of seized and medical cannabis, Sativex® and Dronabinol from two different manufacturers, using a validated LC-MS/MS method. Analytes included delta-9- tetrahydrocannabinol, tetrahydocannabinolic acid A, cannabidiol, cannabidiolic acid, cannabigerol, cannabigerolic acid, cannabinol, cannabinolic acid, cannabichromene, cannabichromenic acid, cannabicyclol, cannabicyclolic acid, tetrahydrocannabivarin, tetrahydrocannabivarinic acid, cannabidivarin and cannabidivarinic acid. Resultant cannabinoid profiles were compared, and markers were suggested. Characteristics of Sativex® included a specific cannabidiol/tetrahydrocannabinol ratio and presence of cannabichromene, while acidic cannabinoids, cannabigerol and cannabinol occurred in only low amounts. As expected, the predominant ingredient in Dronabinol was tetrahydrocannabinol, but minor cannabinoids were quantified as well. Medical marihuana and seized cannabis were compared separately in a principal component analysis. Several medical marihuana varieties were found to significantly differ from seized cannabis, mostly regarding contents of tetrahydocannabinolic acid A and tetrahydrocannabivarinic acid and cannabidiolic and cannabidivarinic acid respectively.

Simultaneous quantification of 18 different phytocannabinoids in serum using a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

The potential therapeutic effects of various phytocannabinoids and the availability of multiple cannabis-based medicines make it desirable to have an analytical method that simultaneously quantifies a wide range of cannabinoids in blood, beyond delta-9-tetrahydrocannabinol and its metabolites. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of 18 phytocannabinoids and cannabinoid metabolites in serum was developed and validated. The method enables simultaneous detection of delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene, cannabicyclol, tetrahydrocannabivarin and cannabidivarin and their acidic precursors tetrahydocannabinolic acid A, cannabidiolic acid, cannabinolic acid, cannabigerolic acid, cannabichromenic acid, cannabicyclolic acid, tetrahydrocannabivarinic acid and cannabidivarinic acid as well as the delta-9-tetrahydrocannabinol metabolites 11-hydroxy-tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol. Limits of detection ranged from 0.0004 to 1 ng/mL and limits of quantification ranged from 0.004 to 2 ng/mL. Calibration curves of all analytes were linear over the whole calibration range. Recovery rates of 52 to 86% were obtained for all analytes except for cannabicyclol (49%), 11-nor-9-carboxy-tetrahydrocannabinol (46%), cannabichromenic acid (44%) and cannabidivarinic acid (36%). Acceptable bias and precision data were demonstrated for all analytes. The method was successfully applied to 55 forensic serum samples, obtained from the Institute of Legal Medicine Mainz.

The synthetic cannabinoid 5F-MDMB-PICA: A case series.

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1-16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected. In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected. The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech. Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases.

Differentiation of ante-mortem and post-mortem fractures with MRI: a case report.

We describe a case of a fatal speed flying accident in which the victim was electrocuted, burned and fell from a great height. Post-mortem imaging revealed acute appearing fractures on CT, without bone marrow oedema on MRI. Based on the known clinical imaging findings of bone marrow oedema in acute fractures, we concluded that the speed flyer died from electrocution rather than the fall and that the fractures occurred post-mortem. Radiological imaging augmented the reconstruction of the peri-mortem events. Further research is needed to assess whether bone marrow oedema in acute fractures is a reliable vital sign.