Background: New psychoactive drugs appeared in Reunion Island beginning in 2016, principally synthetic cannabinoids such as “tabac chimique”. We described the clinical features of twelve hospitalizations during 2023–2024 requiring admission to intensive care unit for suspected psychoactive drug intoxication with atypical clinical presentation for synthetic cannabinoids, including a morphine-like toxidrome. Results: Over a ten-month period, twelve patients aged from 21 to 43 years required treatment in the intensive care unit with a suspected psychoactive drug intoxication. The main cause of intensive care unit admission was a profound coma with early acute respiratory failure. All patients except one developed acute respiratory distress syndrome, with six being severe and ten requiring intubation with mechanical ventilation. Four patients experienced hemodynamic shock. Five exhibited acute heart failure, with three requiring inotropic drugs. Five patients developed acute renal failure and one patient developed acute liver failure. Most of the patients confirmed inhaling “tabac chimique”. Two blood and urine samples were positive for the novel synthetic opioid Protonitazene, one was associated with a novel synthetic cannabinoid. Another analysis was positive for a metamphetamine analogue. Conclusions: Inhalation of new psychoactive substances including novel synthetic opioids can lead to severe organ failure with a life-threatening prognosis, with neurological and respiratory failure initially, followed by early acute cardiac failure. © 2025 The AuthorsRead less <