Since 2010, there has been a new round of drug crises in the United States. The abuse of opioids has led to a sharp increase in the number of people involved in drug crimes in the United States. There is an urgent need to explore solutions to the drug crisis in the United States. In this paper, the model of in-depth analysis is established under the condition of obtaining the opioid data and the influence factor data of the large sample of five state. In the first part, we use the Highway Safety Research Institute model based on the differential equation model to predict the initial value, find the initial position of the drug transfer, and obtain the curve of the number of different groups over time by fitting the data, so that the curves can be predicted the changing trends of the groups in the future. It was found that in Kentucky State, the county’s most likely to start using opioids were Pike and Bale. In Ohio, the county’s most likely to start using opioids are Jackson and Scioto. In Pennsylvania State, Mercer and Lackawanna are the counties most likely to start using opioids. Martinsville and Galax are the counties where Virginia State is most likely to start using opioids. Logan and Mingo are the counties where West Virginia State is most likely to start using opioids. In the second part, the gray prediction model is used to further analyze the time series of each factor, the maximum likelihood estimation method is used to obtain the weight of each factor, and the weight coefficient matrix is used to simulate the multivariate regression equation, and the factors that have the greatest influence on opioid abuse are educational background and family composition. In the third part, the hypothesis test model of two groups (the data type is proportional) is used to verify the difference between the influence factors (including the predicted values) in the first two parts of the states, thus verifying the feasibility between them. At the same time, we put forward a few suggestions to combine the current situation in the United States with the CDC data. We believe that in order to address the opium crisis, the U.S. government needs to strengthen not only oversight of doctors' prescriptions, but also make joint efforts of all sectors of society to fundamentally reduce the barriers to the use of opioids.