(A) In the left, changed metabolites in 20 mg/kg cocaine group exhibit similar changes with combinational drugs group, sharing 10 overlapped metabolites. In the right, a part of modified metabolites showed considerable overlap between 20 mg/kg cocaine group and 2 mg/kg cocaine group or nicotine group. Among them, two shared metabolites between 2 mg/kg cocaine group and nicotine group are Glu and 1-methylhistidine; four shared metabolites between 2 mg/kg cocaine group and 20 mg/kg cocaine group are Gln, L-methionine, α-ketoglutaric acid and phosphocholine; four shared metabolites between nicotine group and 20 mg/kg cocaine group are tryptamine, Lac, Cre and proline. (B) Blue metabolites are upregulated, and red metabolites are downregulated.