A single composition comprising: a) an immediate-release formulation of methylphenidate or a pharmaceutically acceptable salt thereof; and b) a delayed and pulsatile release formulation of ondansetron or a pharmaceutically acceptable salt thereof; for use in a method of treating a substance-related disorder, wherein an in vitro release profile of the methylphenidate or pharmaceutically acceptable salt thereof in the immediate-release formulation is a dissolution rate greater than or equal to 80% in less than or equal to 1 hour or greater than or equal to 90% in less than or equal to 2 hours under simulated gastric or intestinal dissolution test conditions, wherein an in vitro release profile of the ondansetron or pharmaceutically acceptable salt thereofin the delayed and pulsatile release formulation is a dissolution rate of less than or equal to 10% in greater than or equal to 3 hours and greater than or equal to 80% in less than or equal to 7 hours under simulated gastric or intestinal dissolution test conditions, and wherein the substance-related disorder includes psychostimulant use disorder, tobacco use disorder, alcohol use disorder or cannabis use disorder. a) an immediate-release formulation of methylphenidate or a pharmaceutically acceptable salt thereof; and b) a delayed and pulsatile release formulation of ondansetron or a pharmaceutically acceptable salt thereof; for use in a method of treating a substance-related disorder, wherein an in vitro release profile of the methylphenidate or pharmaceutically acceptable salt thereof in the immediate-release formulation is a dissolution rate greater than or equal to 80% in less than or equal to 1 hour or greater than or equal to 90% in less than or equal to 2 hours under simulated gastric or intestinal dissolution test conditions, wherein an in vitro release profile of the ondansetron or pharmaceutically acceptable salt thereofin the delayed and pulsatile release formulation is a dissolution rate of less than or equal to 10% in greater than or equal to 3 hours and greater than or equal to 80% in less than or equal to 7 hours under simulated gastric or intestinal dissolution test conditions, and wherein the substance-related disorder includes psychostimulant use disorder, tobacco use disorder, alcohol use disorder or cannabis use disorder. for use in a method of treating a substance-related disorder, wherein an in vitro release profile of the methylphenidate or pharmaceutically acceptable salt thereof in the immediate-release formulation is a dissolution rate greater than or equal to 80% in less than or equal to 1 hour or greater than or equal to 90% in less than or equal to 2 hours under simulated gastric or intestinal dissolution test conditions, wherein an in vitro release profile of the ondansetron or pharmaceutically acceptable salt thereofin the delayed and pulsatile release formulation is a dissolution rate of less than or equal to 10% in greater than or equal to 3 hours and greater than or equal to 80% in less than or equal to 7 hours under simulated gastric or intestinal dissolution test conditions, and wherein the substance-related disorder includes psychostimulant use disorder, tobacco use disorder, alcohol use disorder or cannabis use disorder.