The resurgence of synthetic cannabinoid receptor agonists as adulterants in the Era of Cannabis legalization: Lessons from prior epidemics and clinical implications

Momentum towards legalization of medical and recreational cannabis drives a convergence between natural cannabinoids and their synthetic counterparts, creating new clinical challenges in a second wave of exposures. This review critically examines the emerging challenges posed by synthetic cannabinoid receptor agonists (SCRAs) and semi-synthetic cannabinoids, emphasizing their clinical implications. SCRAs are potent full agonist activity that have been identified as adulterants in several recreational substances, including cannabis and opioids. Adulteration often leads to unpredictable clinical outcomes and exacerbates the potential for drug interactions. Drawing parallels with other drug epidemics, this paper highlights the urgent need for clinical preparedness to address the nuanced presentations of cannabinoid toxicity, stressing the importance of patient history, physical examination, and judicious use of supportive laboratory tests. This review serves as a cautionary tale and call to action for researchers and policymakers. There is a clear need for robust quality control measures, enhanced public awareness campaigns, and development of evidence-based clinical guidelines to mitigate the health risks associated with intentional and unintentional use of synthetic cannabinoids.