4F-MDMB-BICA toxicity: a fatal case and literature review of synthetic cannabinoid fatalities.

We report the death of a 32-year-old woman with a history of tobacco smoking who was found dead in her car after being investigated 18-days prior in hospital following a road traffic accident. Postmortem examination showed no evidence of recent injury. The most significant finding on internal examination was severe single-vessel coronary atherosclerosis. The remainder of the autopsy showed smoking-associated lung changes. Toxicologic studies were negative for common medications, usual street drugs and alcohols, but specialized analytical testing, developed in-house, identified the indazole-based fluorinated synthetic cannabinoid (SC) 4F-MDMB-BICA and its butanoic acid metabolite in blood, vitreous fluid and urine. An unlabeled package of a herbal smoking mixture, located in the personal belongings of the deceased, was found to contain 4F-MDMB-BICA. The potency of 4F-MDMB-BICA is reported to be much higher (up to several 100-fold) than marijuana. Reported fatalities related to SCs suggest that their effects are unpredictable and, due to the limited studies available, no clear threshold for a lethal dose has yet been determined. Adverse central nervous system effects documented for 4F-MDMB-BICA include auditory and visual hallucinations, paranoia, agitation, confusion, and insomnia. Euphoria, irregular heartbeat, chest pain and myocardial infarction in teenagers have also been described. SCs pose a substantial risk for cardiac toxicity, with mechanisms involving CB1 receptor-mediated oxidative stress, ion channel modulation, and autonomic dysregulation, resulting in a wide range of potentially life-threatening cardiovascular events. Genetic studies were undertaken to rule out a possible cardiomyopathy based on the presence of epsilon waves in a recent hospital electrocardiogram. This revealed a c.5329G > A (p.Ala1777Thr) variant of uncertain significance in the MYH7 gene. Detailed heart examination did not show evidence of an underlying cardiomyopathy. Death in this woman was attributed to 4F-MDMB-BICA toxicity, with coronary atherosclerosis listed as a contributing factor given that SC fatalities are considered primarily cardiac in nature, causing/contributing to acute coronary events, such as coronary vasospasm, thrombosis, arrhythmia, and myocardial ischemia.