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Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services.

ABSTRACT: Since late 2019, low-delta-9-tetrahydrocannabinol (THC) preparations adulterated with synthetic cannabinoids (SCs) have been frequently observed in Switzerland. The unawareness of users concerning the presence of SCs and the typically higher potency and toxicity of SCs, when compared with THC, can result in increased health risks. In Switzerland, low-THC (<1%) cannabis products, except hashish, are legal. These products can act as carrier materials for SCs. In this study, cannabis samples and user self-reports received through three drug checking services were collected and analysed, to gain deeper insight into this new phenomenon. Samples were collected from January 2020 to July 2021. Liquid chromatography coupled with high-resolution mass spectrometry was used for the qualitative screening and semi-quantification of SCs, while gas chromatography with flame ionization detector was applied for the quantification of THC and cannabidiol levels. Reported adverse effects were compared between users who consumed adulterated (SC-group) and non-adulterated (THC-group) products. Of a total 94 samples, 50% contained up to three different SCs. MDMB-4en-PINACA was most often detected. All adulterated cannabis flowers contained ≤1% THC. Adulterated hashish also typically presented low THC-levels (median: 0.8%). The SC-group was associated with higher numbers of adverse events (p = 0.041). Furthermore, psychologic (p = 0.0007) and cardiologic (p = 0.020) adverse effects were more profound in the SC-group than in the THC-group. Drug checking services enabled the timely detection and monitoring of new and potentially dangerous trends. Furthermore, due to user-reports, additional valuable information was gained on adverse events associated with the consumption of novel SCs.

SUBMITTER: Monti MC

PROVIDER: S-EPMC9305195 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsDrug checking services provide people who use drugs with chemical analysis results of their drug samples while simultaneously monitoring the unregulated drug market. We sought to identify and synthesize literature on the following domains: (a) the influence of drug checking services on the behaviour of people who use drugs; (b) monitoring of drug markets by drug checking services; and (c) outcomes related to models of drug checking services.MethodsSystematic review. A systematic literature search was conducted in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, Web of Science and Dissertations and Theses Global. Eligible studies were peer-reviewed articles and conference abstracts or grey literature, published in any language since 1990 and including original data on the domains. We assessed risk of bias for quantitative peer-reviewed articles reporting on behaviour or models of drug checking services using National Institutes of Health tools.ResultsWe screened 2463 titles and abstracts and 156 full texts, with 90 studies meeting inclusion criteria. Most (n = 65, 72.2%) were from Europe and used cross-sectional designs (n = 79, 87.7%). Monitoring of drug markets by drug checking services (n = 63, 70%) was the most reported domain, followed by the influence of drug checking services on behaviour (n = 31, 34.4%), including intent to use, actual use and disposal of the drug, and outcomes related to models of drug checking services (n = 17, 18.9%). The most common outcome measures were detection of unexpected substances (n = 50, 55.6%), expected substances (n = 44, 48.9%), new psychoactive substances (n = 40, 44.4%) and drugs of concern (n = 32, 36.5%) by drug checking services.ConclusionsDrug checking services appear to influence behavioural intentions and the behaviour of people who use drugs, particularly when results from drug checking services are unexpected or drugs of concern. Monitoring of drug markets by drug checking services is well established in Europe, and increasingly in North America. Concerns about drug contents and negative health consequences facilitate the use of drug checking services; lack of concern; trust in drug sellers; lack of accessibility of drug checking services; and legal and privacy concerns are barriers to use.

Project description:Synthetic Cannabinoid Receptor Agonists (SCRA), also known as "K2" or "Spice," have drawn considerable attention due to their potential of abuse and harmful consequences. More research is needed to understand user experiences of SCRA-related effects. We use semi-automated information processing techniques through eDrugTrends platform to examine SCRA-related effects and their variations through a longitudinal content analysis of web-forum data.English language posts from three drug-focused web-forums were extracted and analyzed between January 1st 2008 and September 30th 2015. Search terms are based on the Drug Use Ontology (DAO) created for this study (189 SCRA-related and 501 effect-related terms). EDrugTrends NLP-based text processing tools were used to extract posts mentioning SCRA and their effects. Generalized linear regression was used to fit restricted cubic spline functions of time to test whether the proportion of drug-related posts that mention SCRA (and no other drug) and the proportion of these "SCRA-only" posts that mention SCRA effects have changed over time, with an adjustment for multiple testing.19,052 SCRA-related posts (Bluelight (n=2782), Forum A (n=3882), and Forum B (n=12,388)) posted by 2543 international users were extracted. The most frequently mentioned effects were "getting high" (44.0%), "hallucinations" (10.8%), and "anxiety" (10.2%). The frequency of SCRA-only posts declined steadily over the study period. The proportions of SCRA-only posts mentioning positive effects (e.g., "High" and "Euphoria") steadily decreased, while the proportions of SCRA-only posts mentioning negative effects (e.g., "Anxiety," 'Nausea," "Overdose") increased over the same period.This study's findings indicate that the proportion of negative effects mentioned in web forum posts and linked to SCRA has increased over time, suggesting that recent generations of SCRA generate more harms. This is also one of the first studies to conduct automated content analysis of web forum data related to illicit drug use.

Project description:Marijuana substitutes often contain blends of multiple psychoactive synthetic cannabinoids (SCBs), including the prevalent SCBs (1-pentyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-018) and (1-butyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-073). Because SCBs are frequently used in combinations, we hypothesized that coadministering multiple SCBs induces synergistic drug-drug interactions. Drug-drug interactions between JWH-018 and JWH-073 were investigated in vivo for ?(9)-tetrahydrocannabinol (?(9)-THC)-like discriminative stimulus effects, analgesia, task disruption, and hypothermia. Combinations (JWH-018:JWH-073) of these drugs were administered to mice in assays of ?(9)-THC discrimination, tail-immersion, and food-maintained responding, and rectal temperatures were measured. Synergism occurred in the ?(9)-THC discrimination assay for two constant dose ratio combinations (1:3 and 1:1). A 1:1 and 2:3 dose ratio induced additivity and synergy, respectively, in the tail-immersion assay. Both 1:1 and 2:3 dose ratios were additive for hypothermia, whereas a 1:3 dose ratio induced subadditive suppression of food-maintained responding. In vitro drug-drug interactions were assessed using competition receptor-binding assays employing mouse brain homogenates and cannabinoid 1 receptor (CB1R)-mediated inhibition of adenylyl cyclase activity in Neuro2A wild-type cells. Interestingly, synergy occurred in the competition receptor-binding assay for two dose ratios (1:5 and 1:10), but not in the adenylyl cyclase activity assay (1:5). Altogether, these data indicate that drug-drug interactions between JWH-018 and JWH-073 are effect- and ratio-dependent and may increase the relative potency of marijuana substitutes for subjective ?(9)-THC-like effects. Combinations may improve the therapeutic profile of cannabinoids, considering that analgesia but not hypothermia or task disruption was potentiated. Importantly, synergy in the competition receptor-binding assay suggests multiple CB1R-SCB binding sites.

Project description:(-)-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (-)-11-hydroxy-Δ-9-tetrahydrocannabinol ((-)-11-OH-Δ-9-THC), which is psychoactive, and to (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((-)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (-)-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-Glc) and (-)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (-)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((-)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding-alcoholic and/or phenolic-remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (-)-11-OH-Δ-9-THC-Glc in vitro as well as in vivo and to identify the glucuronide by chemically synthesis of a reference standard. For in vitro analysis, pooled human S9 liver fraction was incubated with (-)-Δ-9-THC. Resulting metabolites were detected by high-performance liquid chromatography system coupled to a high-resolution mass spectrometer (HPLC-HRMS) with heated electrospray ionization (HESI) in positive and negative full scan mode. Five different chromatographic peaks of OH-Δ-9-THC-Glc have been detected in HESI positive and negative mode, respectively. The experiment set up according to Wen et al. indicates the two main metabolites being an alcoholic and a phenolic glucuronide metabolite. In vivo analysis of urine (n = 10) and serum (n = 10) samples from cannabis users confirmed these two main metabolites. Thus, OH-Δ-9-THC is glucuronidated at either the phenolic or the alcoholic hydroxy group. A double glucuronidation was not observed. The alcoholic (-)-11-OH-Δ-9-THC-Glc was successfully chemically synthesized and identified the main alcoholic glucuronide in vitro and in vivo. (-)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.

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Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services.

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