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CONTEXT: Synthetic cannabinoids (SCs) are a structurally heterogenous synthetic class of drugs of abuse. The objective was to describe the incidence of acute respiratory failure in Emergency Department (ED) patients with confirmed SC exposure, and to investigate the association between SC overdose with respiratory failure compared to non-SC overdose. METHODS: This was an observational cohort of ED patients ≥18 years with suspected cannabinoid overdose between 2015 and 2020 at two tertiary-care hospitals. Patient serum was analyzed via liquid chromatography/quadrupole time-of-flight mass spectrometry using a library with >800 drugs including novel psychoactive substances. The primary outcome was acute respiratory failure. DISCUSSION: Of 83 patients with suspected cannabinoid overdose, there were 29 confirmed SC overdoses: 5 F-MDMB-PICA (n = 18) and its metabolite 5OH-MDMB-PICA (n = 16), ADB-FUBINACA (n = 4), AB-CHIMINACA (n = 4), AB-FUBINACA (n = 1), AB-PINACA (n = 1), MDMB-4en-PINACA (n = 1), and 4F-MDMB-BINACA (n = 1). Overall, incidence of acute respiratory failure was 31.3% (95%CI 21.6–42.4). Compared to non-SC overdose, confirmed SC overdose was significantly associated with respiratory failure (25.0% SC vs. 4.2% non-SC, p = 0.05). CONCLUSION: This study demonstrates that SCs are associated with respiratory failure. Since respiratory depression is a potentially lethal adverse effect of SC overdose, future research is warranted.

Obesity, insulin resistance, and poor metabolic profile are hallmarks of a high‐fat diet (HFD), highlighting the need to understand underlying mechanisms. Therefore, we sought to determine the effect of succinic acid (SA) on metabolism in high‐fat diet (HFD)‐induced obesity. Animals were randomly assigned to either low‐fat diet (LFD) or a high‐fat diet (HFD). Mice consumed their respective diets for 4.5 months and then assigned to the following groups: (LFD)+vehicle, LFD + SA (0.75 mg/ml), HFD + vehicle, or HFD + SA. Body weight (BW), food, and water intake, were tracked weekly. After 6 weeks, insulin, glucose, and pyruvate tolerance tests were completed, and spontaneous physical activity was assessed. Epididymal white adipose tissue (EWAT) mass and in vitro measurements of oxidative skeletal muscle (soleus) respiration were obtained. Expectedly, the HFD increased BW and EWAT mass, and reduced glucose and insulin tolerance. SA significantly reduced EWAT mass, more so in HFD (p .05). A significant (p, Obesity, insulin resistance, and poor metabolic profile are hallmarks of a high‐fat diet (HFD), highlighting the need to understand underlying mechanisms and potential treatments. In the HFD‐induced model of obesity, with marked insulin resistance, we treated mice with succinic acid, a metabolite, and complex II agonist. Succinic acid had no positive effect on glucose regulation, but seemed to reduce adiposity, and increase mitochondrial respiratory capacity in oxidative skeletal muscle, likely due to a succinic acid‐induced mitochondrial biogenesis.