Background: Toxicity by synthetic cannabinoids (SCs) is increasing steadily with limited data concerning their use. Serious adverse effects after acute exposure to SCs include myocardial ischemia, stroke, seizures, coma, and acute kidney injury. Aim: Characterization of the epidemiological pattern of acute toxicity by SCs in patients presented to Poison Control Center of Ain Shams University hospitals (PCC-ASUH), Cairo, Egypt; from January 2018 to June 2019, and severity assessment using poisoning severity score (PSS). Methods: A cross-sectional study included adult patients presented to emergency department of PCC-ASUH from January 2018 to June 2019, with history of acute exposure to SCs. Results: About 541 patients attended the PCC-ASUH with history of acute SCs toxicity and only 448 patients were enrolled to our study. Males outnumbered females (96.43 versus 3.57%, respectively). Strox predominated (72.54%) followed by voodoo (27.45%). Recorded PSS was minor in 42.63% of patients, moderate in 18.97% and severe in 5.36%. Two patients (0.45%) died. Metabolic abnormalities predominated (60%), followed by gastrointestinal manifestations (46.2%). Conclusion: Incidence of SCs toxicity has recently increased. Several variables could worsen PSS in acute SCs poisoning like age, sex, type of SCs, co-ingestion, medical comorbidities, and respiratory acidosis. Recommendations: Early combination of PSS and arterial blood gas analysis could help in identifying patients at risk for acute SCs toxicity.