Presence of a synthetic cannabinoid, MDMB-INACA, in "Chimique" in Mayotte: preliminary data on metabolism with a view to a future epidemiological study based on wastewater (2025)

Global consumption of new psychoactive substances is now reaching epidemic proportions. Among new psychoactive substances, synthetic cannabinoid receptor agonists challenge the monitoring framework due to the continuing growth in their numbers, which are increasing by around 20 molecules a year. We report data related to MDMB-INACA, a synthetic cannabinoid receptor agonist detected during the "Chasse-marée" study, carried out in Mayotte, a French overseas territory located in the Mozambique Channel: in addition to reporting its detection in samples of consumed products (called "Chimique") and to estimating consumer profiles via a self-administered questionnaire, we studied its metabolism in order to plan a wastewater monitoring project. In order to determine the involved molecules, sample of "Chimique" (the local name of a cigarette containing synthetic cannabinoids in the West Indian Ocean) were collected 1 week a month between September 22 and 23. Samples were collected from users by individual solicitation and a structured interview was proposed. Analyses were performed using liquid chromatography coupled with high-resolution mass spectrometry, and a metabolism study was carried out in silico and in vitro using human liver microsomes. One of the most found molecules was MDMB-INACA, often in tandem with MDMB-4en-PINACA. Sixty-four cigarettes contained MDMB-INACA out of 190 samples collected, and the mean concentration of MDMB-INACA in these samples of "Chimique" was 10.5 +/- 13.6 µg/mg. The ultimate goal of this intensive fieldwork being to develop an epidemiology based on wastewater analysis, the MDMB-INACA metabolites were explored: the metabolite resulting from the hydrolysis of the carboxylic acid ester appears to be the most valuable target for wastewater-based epidemiology as MDMB-INACA biomarker. To a lesser extent, conjugated hepatic glucuronides (O-glucuronide metabolite and N-glucuronide metabolite) can serve as useful biomarkers for the analysis of biological media (blood, urine) from intoxicated victims, but their deconjugation in wastewater rules them out as analytical targets in wastewater-based epidemiological studies. This metabolite resulting from the hydrolysis of the carboxylic acid ester may be proposed as an analytical target for a wastewater monitoring project, but the present work also outlines the further studies needed to monitor MDMB-INACA in wastewater: metabolisation rates and in vitro, or even in situ, stability experiments need to be carried out. [Author's abstract]