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A multi-analyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described, involving the separation of delta-9-tetrahydrocannabinol (delta-9-THC) and delta-8-THC in addition to other commonly encountered drugs and metabolites. Briefly, sample preparation involved an alkaline liquid-liquid extraction (methyl tert-butyl ether) of blood (100 μl). The solvent layer was transferred, evaporated to dryness, reconstituted, and samples then separated on an Agilent Poroshell 120 EC-C18 100 Å (50 mm × 3.0 mm, 2.7 μm) analytical column using a multi-step gradient elution of 50 mM ammonium formate in water (pH 3.5) and 0.1% formic acid in methanol over 14 min. A SCIEX Triple Quad 6500+ system operating in scheduled multiple reaction monitoring and positive electrospray ionization was used for detection. There were no interferences, and matrix effects were generally acceptable (±20% of neat response). Linearity was achieved within the calibration range, including methylamphetamine (MA) (10-1000 ng/ml), 3,4-methylenedioxy-N-methylamphetamine (MDMA) (10-1,000 ng/ml), cocaine (10-1000 ng/ml), and two THC isomers (1-100 ng/ml). Accuracies of MA, MDMA, cocaine, and two THC isomers were 3.6 to 8.9%, -1.2 to 4%, -5.3 to 5.8%, and -11 to 14%, respectively; while precision estimates of the same were 1.6 to 5.4%, 1.7 to 5.3%, 1.2 to 4.5%, and 2 to 10%, respectively. Autosampler stability and dilution integrity were within acceptable limits, and no carryover was detected at the limit of detection. This validated LC-MS/MS method made the routine identification of both delta-9-THC and delta-8-THC in blood possible., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Gas chromatography-mass spectrometry (GC-MS) is widely used for the identification of cannabinoids in seized plant material. Conditions used for instrumental analysis should maximize decarboxylation, while minimizing the in situ production of Δ9-THC inside the GC inlet. In this study, decarboxylation of the acidic Δ9-THC precursor and in situ degradation of cannabidiol (CBD) were investigated using seven commercial GC liners with different deactivation chemistries and geometries. While the inlet temperature was previously optimized at 250°C in a previously validated assay, we systematically examined the temperature-dependent decarboxylation of tetrahydrocannabinolic acid-A (Δ9-THCA-A) and cyclization of CBD between 230°C and 310°C using different liners using favorable and unfavorable conditions. Significant differences in decarboxylation rate and CBD cyclization were observed between different liner types. While no temperature-dependent differences in decarboxylation rate were observed within liner type, liner-dependent differences were observed (α = 0.05), particularly between those with different geometry. In contrast, temperature and liner-dependent differences were observed for in situ formation of Δ9-THC (α = 0.05). This was influenced by liner geometry and to a smaller extent by surface deactivation. Effects were exacerbated with liner usage. While significant differences were observed using new and used GC liners, differences between liners of the same type but different lot numbers were not observed. Inter-instrument differences using the same liner were also evaluated and had minimal effect. Liner- and temperature-dependent effects were also confirmed using more than 20 cannabis plant extracts. Careful selection of liner, inlet conditions, and regular preventive maintenance can mitigate the risks associated with in situ formation Δ9-THC from CBD., (© 2023 John Wiley & Sons, Ltd.)

The stability of cannabinoids is complex and crucial for the assessment of impaired driving caused by cannabis. Therefore, the effect of antioxidants on the long-term stability of Δ 9 -tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-hydroxy-Δ 9 -tetrahydrocannabinol (THC-OH), and 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH) in whole blood samples preserved with fluoride citrate (FC) and fluoride oxalate (FX) mixtures was investigated at different temperatures. The measured concentrations of the cannabinoids in authentic whole blood preserved solely with FC or FX mixtures decreased significantly during prolonged storage at -20°C. On average, less than 5% of the initial concentrations of THC and CBD were recovered after 19 weeks of storage interrupted by 5 thawing/freezing cycles. The rate of decrease was greatest in FC-preserved blood. The repeated thawing/freezing of the samples accelerated the instability progression. At 5°C approximately 60% of the initial concentrations of THC and CBD were recovered after 19 weeks of storage. No significant decrease was observed in samples stored at -80°C during the test period of 5 months. The instability at -20°C was to a great extend avoided by adding 30 mM ascorbic acid (ASC) to the samples before storage. Samples preserved with a combination of the FX mixture and ASC showed no significant decrease in the recovered concentrations during a 5-month storage period interrupted by 6 thawing/freezing cycles. Samples preserved with a combination of the FC mixture and ASC showed almost similar improvements in cannabinoid stability. Other reducing agents such as sodium metabisulfite and glutathione also improved the stability in FX-preserved blood stored at -20°C., (Copyright © 2017 John Wiley & Sons, Ltd.)

Cannabis is the most widely used illicit substance globally, with an estimated annual prevalence in 2010 of 2.6-5.0% of the adult population. Concerns have been expressed about increases in the potency of cannabis products. A high tetrahydrocannabinol (THC) content can increase anxiety, depression, and psychotic symptoms, and can increase the risk of dependence and adverse effects on the respiratory and cardiovascular systems in regular users. The aim of this study was to report statistical data about the potency of cannabis products seized in the north-east of Italy, in a geographical area centred in Venice and extending for more than 10,000  km(2) with a population of more than two million, by investigating the variability observed in THC levels of about 4000 samples of cannabis products analyzed over the period 2010-2012. Overall median THC content showed an increasing trend over the study period from about 6.0% to 8.1% (6.2-8.9% for cannabis resin, 5.1-7.6% for herbal cannabis). The variation in the THC content of individual samples was very large, ranging from 0.3% to 31% for cannabis resin and from 0.1 to 19% for herbal cannabis. Median CBN:THC ratios showed a slightly decreasing trend over the study period, from 0.09 (2010) to 0.03 (2012), suggesting an increasing freshness of submitted materials. Median CBD:THC ratios also showed a decreasing trend over the study from about 0.52 (2010) to 0.18 (2012), likely due to the increase in submissions of materials from indoor and domestic cultivation with improved breeding methods., (Copyright © 2013 John Wiley & Sons, Ltd.)

Since early 2009, over 80 illicitly produced synthetic cannabinoid receptor agonists have been notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Yet more have been reported in other countries or offered for sale on websites. These cannabinoids typically act as agonists at CB1 receptors, and mimic the effects of Δ(9)-tetrahydrocannabinol (THC), the principal psychoactive constituent of Cannabis L. As with other 'new psychoactive substances', they have shown the limitations of current drug control procedures. First, the regular appearance of new compounds makes specific listing impractical and overwhelms any attempt to create risk assessments on a substance-by-substance basis. Secondly, the lack of human pharmacological and toxicological data hinders any objective attempt to show that synthetic cannabinoids are harmful. The UK has had a long experience of using generic legislation to control groups of compounds. However, cannabimimetic activity arises in a large number of distinct chemical families, and it is clear that generic control can no longer cope with this diversity whilst remaining intelligible to non-chemists. Analogue control presents further difficulties, and does not appear to offer an acceptable solution. For these reasons, legislatures in many countries are creating novel forms of regulation separate from domestic drug laws. The generic definition of classical cannabinoids, introduced into the UK Misuse of Drugs Act in 1971, also shows signs of weakness. Thus the growing interest in the clinical potential of tetrahydrocannabivarin (THCV) is inhibited, at least in the UK, by its unintended status as a Schedule 1 substance., (Copyright © 2013 John Wiley & Sons, Ltd.)

The average potency of illicit marijuana in the USA has increased substantially over the past four decades, and observers have suggested a number of likely reasons for this. One set of hypotheses points to a market that has evolved from foreign to domestic sources of supply, and to continuing advances in sophisticated cultivation techniques. Another set of hypotheses points to testing artifacts related to changes in the sampling, handling, and testing of illicit marijuana. The current study uses data from the federally sponsored Potency Monitoring Program, which performs ongoing forensic analysis of seized marijuana samples, to assess the extent to which the observed increase in cannabis potency in the USA between 1970 and 2010 is a function of genuine shifts in illicit marijuana markets or testing artifacts related to changes in the quality of seized marijuana. The study finds, after adjusting for marijuana quality, that the apparent 10.5 factor increase in mean reported THC% between the 1970s and the 2000s is instead on the order of a six- to seven-fold increase. By this accounting, then, the reported long-term rise in potency is roughly 57-67% as great when the quality of the tested marijuana is taken into account. This study's findings, therefore, caution against the uncritical use of potency monitoring data and highlight the importance of assessing potency measurement reliability and addressing data quality issues in future policy analytic research., (Copyright © 2012 John Wiley & Sons, Ltd.)