The main purpose of this study is to determine the outcome of a drug combination treatment on detoxified and stabilized methamphetamine (METH) and/or cocaine (COC) dependent users. The combination regimen consists of oral administration of a generic immediate-release methylphenidate (MPh-IR) formulation (e.g., Ritalin®) and a novel delayed, pulsatile-release formulation of the antiemetic ondansetron (Ond-PR002). Various psychological assessment tools and functional magnetic resonance imaging (fMRI) will be used to assess the treatment outcome. In addition to the treatment outcome measures, we will determine whether the 14-day, once-a-day treatment leads to significant changes in the pharmacokinetic/pharmacodynamic (PK/PD), safety and tolerability parameters of MPh-IR and/or Ond-PR002 formulations and drug-drug interactions between the two drugs.

Inclusion Criteria:

• Subjects must give written informed consent.
• Detoxified METH/COC-dependent male and/or female subjects between 18 and 45.
• Females with Body Mass Index (BMI) of 18-36 kg/m2. Males with BMI of 20-36 kg/m2.
• Subjects in good health determined by screening examination.
• Subject must have adequate veins for intravenous site.
• Subjects must be mentally stable for minimum of 3 months.
• Non-clinically significant hematology clinical laboratory results.
• Subjects must have hematocrit of greater than or equal to 33%.
• Non-clinically significant screening 12-lead ECG and QT interval (time for ventricular depolarization and repolarization to occur) corrected by Fridericia formula (QTcF) of < 440 msec for male and < 460 msec for females.
• Subjects must be right-handed (control for handed-related differences) in lateralized patterns of brain function.
• Ability to identify visual cues during fMRI.
• Subjects' VAS score must be above 20.

Exclusion Criteria:

• Subjects who consume more than 28 units of alcohol per week.
• Subjects who test positive for drugs of abuse or alcohol.
• Current use of nicotine replacement therapy or other smoking cessation treatment.
• Use of other investigational drugs within 30 days, or at least 5 half-lives of a study medication prior to enrollment.
• Subjects being treated with other psychotropic drug will be excluded based on PI's clinical judgment and potential drug-drug adverse reactions with study drugs.
• Subjects on prescribed, over-the-counter (OTC) or nutraceutical drugs that may influence the PK, safety or efficacy profiles of MPh-IR and/or Ond-PR002 will be excluded, or receive a washout prior to study enrollment. Subjects on drugs or substances known to be strong inhibitors or strong inducers of CYP 3A4/5 enzymes (enzymes involved in the metabolism of xenobiotics) or P-glycoprotein (P-gp) will be excluded in a similar manner.
• Subjects with heart disease or uncontrolled high blood pressure.
• Donation of any blood or plasma in the last month, or donation of >500mL of blood within the 3 months preceding study drug administration.
• History of serious adverse reaction or allergies to any drug or any other products used in the study.
• Allergies or intolerance to any of the products used in this study.
• Subjects who have allergies to pork-derived medications or those that contain pork-derived products.
• Inability to give informed consent or high likelihood of being unable to complete the necessary confinement.
• Subjects deemed inappropriate for this study by the Principal Investigator.
• Subjects with a documented brain abnormality, history of unexplained loss of consciousness, seizures, history of unexplained syncope, or history of transient ischemic attack or stroke within the past 6 months.
• History of concurrent illness that required hospitalization within 14 days prior to Day 1 or a clinically significant illness within 4 weeks prior to Day 1.
• History of clinically significant cardiovascular illness within the past 6 months.
• History of clinically significant hepatic, renal, pulmonary, metabolic, endocrine, infectious, gastrointestinal, hematologic, oncologic, retinopathy, or other medical disorders.
• History of unstable psychiatric illness requiring hospitalization within previous 6 months.
• Subjects with history of glaucoma, color blindness or other uncorrected vision problem.
• Subjects with QTcF interval duration greater than or equal to 440 msec (males) or greater than or equal to 460 msec (females) obtained from the 12-lead ECG recorder's measurements on the screening ECG.
• Individuals with a major condition that would make fMRI participation unsafe or uncomfortable.
• Females who are pregnant, breast-feeding or plan on becoming pregnant.
• Subjects who have a hematocrit < 33% or hemoglobin < 12.0 g/dL.