This study will determine the influence of methylphenidate (e.g., Ritalin®) and duloxetine (Cymbalta®), alone and in combination, on the cocaine use as measured by self-report and urine drug screens.

Inclusion Criteria:

• Recent cocaine use
• Seeking treatment for cocaine use

Exclusion Criteria:

• Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant
• Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion
• History of serious physical disease or current unstable physical disease (e.g., past myocardial infarction, uncontrolled hypertension, diabetes, head trauma, seizures or CNS tumors) or current or past histories of serious psychiatric disorder or suicidal risk, other than substance abuse or dependence, will be excluded from research participation
• Females not currently using effective birth control
• Contraindications to cocaine, methylphenidate or duloxetine
• Currently using opioids for pain or who are currently maintained on methadone or buprenorphine for opioid use disorder will be excluded from participation
• Body weight less than 50 kg

Data will be shared per NIH policy. Individual participant data will not be shared.