Opioid (commonly called narcotic) pain medicines are, after marijuana, the most commonly abused substances in the United States. Patients who take opioids for legitimate reasons may become addicted; for example, as many as 1 in 4 patients meet the criteria for current opioid dependence. It is very important that a way is found to provide pain relief while minimizing the addiction potential of these widely used pain medications.

The study aim to find out if the use of another type of medication given in addition to an opioid will reduce the addiction potential of the opioid.

The study is trying to find out if the ability of the opioid to relieve pain is changed when given with the other medication, and to see if the euphoric sensation or "liking" of the opioid pain medication is reduced when taken with the other medication.

This study involves the use of an investigational combination of drugs. "Oxycodone with Risperidone" and "Oxycodone with Ziprasidone" are called "Investigational" because the U.S. Food & Drug Administration (FDA) has not approved these drug combinations for the purpose of this study. Individually, each of these drugs is approved by the FDA for other reasons (i.e. oxycodone as a painkiller, while risperidone and ziprasidone are approved as anti-psychotic medications), but the administration of these drugs together has not been studied before or been approved by the FDA for this purpose.

This is the first study involving humans to examine the safety of this combination of drugs and how they work together. The goal of the study is to find out what effects, good and/or bad, it has on people who take them. Because the combination has not been studied in humans before, information about the safety and effectiveness is incomplete and all of the side effects are not yet known.

Inclusion Criteria:

• Requirement of prior exposure to opioids

Exclusion Criteria:

• Presence of psychiatric comorbidity
• Presence of chronic pain disorder
• Presence or history of substance use disorder
• Current analgesic or neuroleptic medication usage (any medication for pain, including over-the-counter analgesics like ibuprofen/acetaminophen)
• Pregnancy
• Positive drug urine test
• Continuous opioid misuse measure score of < 9
• Presence or history of diabetes
• Presence or history of cardiac disease or arrhythmia

Individual participant data will be shared with other collaborating investigators, and unidentified data will be shared at study completion as a publication.

At study completion.

Subjects will be administered one of two fixed dose drug combinations. The control will be oxycodone plus placebo, whereas the treatment groups will receive oxycodone plus one of the two atypical antipsychotics (Risperidone, Ziprasidone) under study. Study drug will be compounded by outside research pharmacy.