The synthetic cannabinoids dominated the market with a detrimental effect on society. Determining the stability of synthetic cannabinoids (SCs) in samples is crucial for accurate detection and quantification in drug testing. Since designer narcotics emerge rather quickly, a new generation of cannabinoid-associated compounds also appears rapidly. Thus, it is crucial to identify, detect, and determine the confidence of drug testing to provide fairer judgments. In this study, we aimed to determine optimal storage conditions to prevent degradation and preserve the samples of four new-generation SCs (MDMB-4en-PINACA, 4-Fluoro MDMB-BICA, 5F-MDMB-PICA, and 5F-MDMB-PINACA) in blood samples due to the lack of available information on the stability. Blood samples were collected from 20 healthy volunteers, treated with cannabinoids at concentrations of 10 and 50 ng/mL, and stored at temperatures of room temperature, +4°C, and -20 °C over 35 days. Our findings revealed a gradual decline in cannabinoid concentrations over time, with 5F-MDMB-PINACA exhibiting the highest degradation rate. Storage temperature significantly influenced degradation rates, with the most rapid reduction observed at room temperature and the slowest degradation at -20 °C. Our findings are a reference study providing valuable insights into the preservation of the samples for the testing of the most prevalent SCs of the present day.