Sex/gender differences in spontaneous reports to a French Addictovigilance centre.

To specify psychoactive substances and related complications observed in spontaneous reports (SRs) in women versus men, we assessed SRs on substance-linked acute toxicity sent to a French Addictovigilance centre. Over the period 2021-2022, 880 SRs were analysed (33.4% concerned women). Severe complications concerned more men than women (70.3% versus 59.5%; p = 0.0014). In women, the main implicated substances were psychoactive medications (opioids, benzodiazepines). The most frequently reported complication was suicidal behaviour (14.6% versus 7.8%, p = 0.002). In men, SRs concerned mainly illicit substances (cocaine, amphetamines) or misuse of opioid maintenance therapy or nitrous oxide. The main complications in men were infections (12.97% versus 5.4%, p = 0.0006) and neurological troubles (37.6% versus 23.5%, p < 0.0001).Our data highlight sex/gender disparities in substance use and complications, in agreement with recent literature and French national Addictovigilance data.

Isotonitazene, a synthetic opioid from an emerging family: The nitazenes.

From 2019, in the United States and Europe, the synthetic opioid market has diversified with the appearance of the 2-benzylbenzimidazole family, commonly named "nitazenes". In vitro studies show that these synthetic opioids have much higher affinities on µ-opioid receptors: 100 times more than morphine, and slightly higher than fentanyl for isotonitazene, increasing the risk of overdose. In south of France, isotonitazene (IZN) was identified for the first time in March 2023. In this context, there were 9 reports concerning the use of IZN in the south of France over a short period (March-April 2023), with identification of IZN in 4 cases and suspicion in others. They concerned 6 men and 3 women, with a mean age of 44.9±2 years. When available (2 cases), the product had been purchased from a dealer. IZN was identified on sample in 2 cases of overdose. Isotonitazene was also identified in biological samples in 2 cases: 1 case of overdose and coma requiring hospitalization with a favorable outcome (urinary analysis), and a death with post-mortem identification. This was the first identification of this product in France. The immediate broadcast of the alert limited the risks for users and made it possible to quickly inform regional and national health authorities. IZN is under intensive surveillance by the EMCDDA and classified as a narcotic in France since 2021. The analysis of the literature made it possible to identify cases of overdoses requiring very high doses of naloxone and deaths. The emergence of these synthetic opioids constitutes an important signal, due to their superior effects to heroin, their incomplete response to naloxone and the current difficulty in identifying them (devices for analyzing products in the reduction of risks, toxicology laboratories).