New synthetic products (NPS) refer to “narcotic or psychotropic drugs, in pure form or in preparation, which are not controlled by the United Nations drug conventions, but which may constitute a threat to public health comparable to that of posed by the substances listed in these conventions”.
Today, users can consume NPS, or otherwise use older substances, in a wide range of situations. NPS includes a variety of substances that mimic the effects of illicit products such as ecstasy, amphetamines, cocaine, cannabis, certain opioids, etc. Their extremely variable composition leads to somatic, psychiatric and cognitive complications. The European Monitoring Center for Drugs and Drug Addiction has listed 930 NPS, of which 41 were identified for the first time in 2022.
In France, the French Observatory on Drugs and Addictive Tendencies (OFDT) has identified 368 NPS since 2008, including 35 in 2021 according to data from the Sintes system. The main substances include cathinones (stimulants), synthetic cannabinoids and phenethylamines (hallucinogens). A working group led by Professor Laurent Karila and Mildeca has developed a brochure intended for professionals, identifying the different categories of NPS1. This work also resulted in the development of a free application available on Android and Apple, called NPS PSYCHOACTIFS.
We propose here to highlight the crucial aspects of a particular family of NPS, offering potential means of identification of the use of these substances, in particular to doctors. Additionally, a better understanding of these substances provides an opportunity for poisoning prevention and naloxone management.
The producers of these drugs are constantly evolving the molecular structures of NPS in order to circumvent drug laws. In fact, the legal and regulatory framework does not allow total control of these psychoactive substances. Thus, the first cathinone derivatives were classified as narcotics by decree of July 27, 2012, and since then, legislation has regulated new families or individual substances.
Acute poisonings and deaths continue to increase in view of the increasing use of NPS in festive environments or during sports practices. chemsex Chemsex covers all of the relatively new practices that have appeared among certain men who have sex with men (MSM), combining sex, most often in groups, and the consumption of synthetic psychoactive products. (consumption of psychoactive substances in a sexual context) and sometimes criminal chemical submission. The French addictovigilance network alerted on the importance of notified cases (all ages and in all regions). Thus, 800 serious cases of abuse or somatic complications were reported over the period 2009-2017, of which 71 led to deaths (i.e. nearly 9%).2. In a context marked by a constant increase in online purchases of psychoactive substances, it is imperative to remain extremely vigilant in the face of the growing availability of NPS and the significant health risks they cause.
This issue is of particular importance in emergency services and intensive care, where a treatment protocol is distributed. Beyond the clinical aspects, the addiction liaison and care teams (Elsa) are alerted to initiate specialized care, while the evaluation and information centers on drug dependence-addictovigilance (CEIP-A) analyze and evaluate the clinical complications linked to these substances.
More generally, any health or medico-social sector professional may have to question the identification of a substance, its effects and the associated risks. Substances are classified into 20 families according to the initial molecules from which they come (table 1).
-Family of new synthetic opioids (NOS)
In addition to pharmaceutical fentanyls (fentanyl, sufentanil, remifentanil, alfentanil), new synthetic opioids (NOS) initially developed for therapeutic purposes are now produced in clandestine laboratories. NOS are new psychoactive substances with high pharmacological potency, easy availability on the Internet, low price, high purity and which cannot at this stage be detected in routine toxicology laboratory tests3.
They come in different forms (powder, tablets, etc.) and are consumed orally, intranasally, intravenously, mainly with impressive pharmacological potencies (table 2).
The desired effects are euphoric and sedative, “heroin-like”, with relaxation and analgesia. The onset of action is rapid (a few minutes) and the duration of action is short (a few hours). They are classified as “depressants”. Acute poisoning or overdose is a serious complication (respiratory depression, cyanosis, miosis, drowsiness, altered consciousness, bradycardia, nausea, anxiety and abdominal pain/coma).
Naloxone as an antidote4
Management of synthetic opioid overdoses must be done by intravenous or intranasal administration of naloxone, a μ-opioid receptor antagonist. However, the administered dose of naloxone to reverse NOS poisoning must sometimes be higher than those used for heroin or morphine overdoses, or even require repeated administrations at the risk of secondary respiratory depression.
Between 2013 and 2019, death rates (age-adjusted) from synthetic opioids increased by 1,040% in the United States. In 2021, EU member states reported around 140 deaths associated with the misuse of fentanyl from medical use.
In France, several deaths are reported in the DRAMES addictovigilance survey5as recently with nitazenes. The French Association of Addictovigilance Centers warns against the arrival of nitazenes in mainland and overseas France. Thus, the November 2024 bulletin produces an assessment of the situation and returns to the key points.
Legislative framework
« 3-fluorofentanyl » ;
« 4-fluorobutyr(yl)fentanyl » ;
« 4-méthoxybutyr(yl)fentanyl » ;
« acryl(oyl)fentanyl » ;
« beta-hydroxythiofentanyl » ;
« carfentanil ou carfentanyl » ;
« despropionylfentanyl » ;
« despropionyl-2-fluorofentanyl » ;
« furanylfentanyl » ;
« isobutyr(yl)fentanyl » ;
« methoxyacetylfentanyl » ;
« ocfentanil ou ocfentanyl » ;
« para-chloroisobutyrfentanyl or
4-chloroisobutyrfentanyl » ;
« para-fluoroisobutyr(yl)fentanyl ou
4-fluoroisobutyr(yl)fentanyl ou 4F-iBF » ;
« tetrahydrofuranylfentanyl ou THF-F » ;
« valerylfentanyl »
are classified on the list of narcotics (JO order of September 8, 2017). Isotonitazene, brorphine, metonitazene are classified on the list of narcotics (ANSM decision of August 30, 2023).
