Adverse clinical effects associated with the use of synthetic cannabinoids: A systematic review

Synthetic cannabinoids (SCs) are potent agonists of CB1 and CB2 receptors, with affinities approximately 100 times greater than that of natural cannabis. This increased potency is associated with severe clinical outcomes, including psychosis, dependence, and various autonomic disturbances, such as seizures and rhabdomyolysis. The objective of this study was to synthesize the existing literature on the clinical effects of SCs, emphasizing health risks and identifying knowledge gaps. Following PRISMA guidelines, a comprehensive search was conducted across three databases-PubMed, Embase, and Lilacs-resulting in 944 studies. Eligible articles focused on clinical effects associated to SC use, while exclusion criteria encompassed studies unrelated to clinical outcomes, other reviews, animal studies, and those concentrating solely on psychiatric symptoms or therapeutic uses of SCs. In total, 49 studies published between 2010 and 2022 were included, representing diverse populations and study designs. Participants were predominantly young adult males, although ages ranged from 12 to 72 years. SCs' clinical effects predominantly affected the neurological and cardiovascular systems, with common symptoms including seizures, altered consciousness, tachycardia, and hypertension. Hospital and ICU admissions varied, reflecting the complex nature of SC toxicity. Compared to cannabis, SC use was linked to more severe cardiovascular and neurological complications. Additional rare complications included thromboembolic events, immune thrombocytopenic purpura, and psychiatric disturbances. This review highlights the urgent need for targeted public health policies to mitigate the risks associated with SC use and improve medical management. It also stresses the importance of further controlled studies to elucidate the underlying mechanisms of these clinical effects and their pharmacological basis.