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Drug stability is an important concern of forensic toxicological testing, particularly postmortem (PM) samples that may be stored for an extensive period of time before analysis. In PM toxicology, the complex assessment of analyte stability in biological matrices can profoundly impact the interpretation of toxicological results and the outcome of forensic casework. The aim of this work is to assess the stability of ∆9-tetrahydrocannabinol (THC), cannabidiol, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-∆9-THC (THCCOOH) and 11-nor-∆9-THC-9-carboxylic acid glucuronide (THCCOOH-glucuronide) in brain stored at three different temperatures (4°C, -20°C and -70°C) up to over 12 months (390 days) in order to establish the best storage condition for preventing potential drug degradation during the storage period. Brain is suitable and useful for xenobiotic concentrations and is a valuable specimen in the interpretation of PM toxicological results. In our study, pooled brain specimens were spiked at low and high concentrations to evaluate the change in concentration over time. Stable compounds were quantified within ±20% of the target concentration (the mean concentration resulting from the initial analysis). According to stability criteria, our preliminary findings revealed that all the cannabinoids studied are stable in frozen brain samples (-20°C and -70°C) for over 12 months: all the analytes' concentrations remained unaffected during storage over time, with the analytical variation staying within ±20%. On the contrary, under refrigeration conditions (4°C), 11-OH-THC, THCCOOH and THCCOOH-glucuronide were instable. Authentic brain samples, collected from eight cases during the autopsy, were analyzed, and the stability was evaluated. This study provided new data on cannabinoid stability in brain. The stability of the brain samples, both in spiked samples and in authentic caseworks, highlights the importance of the brain as a valid testing matrix when retesting is required after a long period of time or when laboratories are faced with backlog., (© Crown copyright 2022.)

The scientific interest in cannabis has been documented by a wide literature, but postmortem studies and interpretations of autopsy findings are lacking or limited to few cases, few matrices analyzed or a small number of analytes. The present study describes the development and full in-house validation of a sensitive and simple method based on an optimized rapid clean-up procedure combined with a robust and highly sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) technique, designed to simultaneous determination of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (THC-COOH) and 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid glucuronated (THC-COOH gluc.) in postmortem samples: central blood (CB), femoral blood (FB) and brain tissue (BR). The developed method was validated and applied to 24 postmortem cases involving cannabinoids. In this study, we presented a full optimization and validation of target analyses for each matrix. The procedure had proven to be reliable and accurate. This study adds new data, particularly about the cannabinoids concentrations in BR samples. Combined pattern (CB, FB, BR) can be used in the interpretation of postmortem cases, proving and strengthening the assessments made on blood data. BR matrix is a helpful supplement in the investigation of the role of cannabinoids as crucial or contributory factor in leading to death., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The recent release of a medical cannabis strain has given a new impulse for the study of cannabis in Italy. The National Health Service advises to consume medical cannabis by vaporizing, in decoction or oil form. This is the first study that explores the pharmacokinetics and tolerability of a single oral dose of cannabis as decoction (200 ml) or in olive oil (1 ml), as a first step to improve the prescriptive recommendations., Methods: This is a single-center, open-label, two-period crossover study designed to assess the pharmacokinetics and tolerability of oral cannabis administered to 13 patients with medication overuse headache (MOH). A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was conducted for the quantification of THC, CBD, 11-OH-THC, THC-COOH, THC-COOH-glucuronide, THCA-A, and CBDA. Blood pressure, heart rate, and a short list of symptoms by numerical rating scale (NRS) were assessed., Results: Decoctions of cannabis showed high variability in cannabinoids content, compared to cannabis oil. For both preparations, THCA-A and CBDA were the most widely absorbed cannabinoids, while THC and CBD were less absorbed. The most important differences concern the bioavailability of THC, higher in oil (AUC 0-24 7.44, 95% CI 5.19, 9.68) than in decoction (AUC 0-24 3.34, 95% CI 2.07, 4.60), and the bioavailability of CBDA. No serious adverse events were reported., Conclusions: Cannabis decoction and cannabis oil showed different pharmacokinetic properties, as well as distinct consequences on patients. This study was performed in a limited number of patients; future studies should be performed to investigate the clinical efficacy in larger populations.