The overall goal of this project is to develop initial human data on effects of novel compounds on safety (interactions with oxycodone) and efficacy (subjective response to oxycodone) in non-treatment seeking opioid use disorder subjects. The compound to be studied will be the 5-HT2CR agonist lorcaserin. There are no known or reported adverse interactions between lorcaserin and oxycodone or other opioids.

Lorcaserin is a serotonin (5-HT) 2C receptor agonist (Trade Name Belviq) approved for treatment of obesity. The study teams's preclinical research collaborators and others have shown that lorcaserin and other 5-HT2CR agonists have been shown to reduce drugs of abuse self-administration and cue reactivity in rodents including cocaine and nicotine. Recently, this data has been expanded to opioids. Rats trained to self-administer oxycodone showed a significant reduction in self-administration and oxycodone cue induced lever presses after lorcaserin administration.

This is a single center, double-blind, placebo-controlled, randomized, 1b/2a study. 18 subjects are planned. The following treatment regimens will be used:

Lorcaserin will be administered at a dose of 10mg twice daily. Placebo or Comparator - identical placebo capsules administered at the same time as lorcaserin.

Inclusion Criteria:

In order to participate in this study, subjects must:

1. Males and females between 18 and 70 years-of-age.
2. Understand the study procedures and provide written informed consent.
3. Meet current DSM-5 criteria for opioid use disorder, at least moderate severity, but are not seeking treatment.
4. Have at least one positive urine drug screen for opioids during screening to document opioid use.
5. Have no clinically significant abnormalities in the judgment of the study physician in hematology and chemistry laboratory tests including liver function tests.
6. Have no contraindications for study participation as determined by medical history and physical examination.
7. Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory testing.
8. No pregnant or nursing women will be permitted in the study, and women must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). Men will be advised to use condoms. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and at the end of study participation.

Exclusion Criteria:

In order to participate in the study, subjects must not:

1. Meet current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, marijuana, cocaine or nicotine. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary (SCID).
2. Have a current DSM-5 axis I psychiatric disorder other than substance use disorder including but not limited to Bipolar Disorder, Major Depressive Disorder, ADHD, or Schizophrenia or a neurological disorder requiring ongoing treatment and/or making study participation unsafe.
3. Have any previous medically adverse reaction to oxycodone or other opioids or lorcaserin.
4. Have any untreated clinically significant medical disorder including cardiovascular, pulmonary, CNS, hepatic, or renal disorder.
5. Have a history of seizures (excluding childhood febrile seizures), or loss of consciousness from traumatic injury for more than 30 minutes.
6. Have significant current suicidal or homicidal ideation or a history of suicide attempt within the past 6 months.
7. Have conditions of probation or parole requiring reports of drug use to officers of the court.
8. Have impending incarceration.
9. Have a positive HIV test by self-report or history.
10. Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests at screening, and daily after hospital admission.
11. Have any other illness, or condition, which in the opinion of the PI would preclude safe and/or successful completion of the study.
12. Have taken any investigational drug within 90 days prior to baseline.
13. Have an allergy to lorcaserin or oxycodone.
14. Have taken or are currently taking drugs that are know to inhibit cytochrome P450, CYP3A or CYP2D6.
15. ECG with QTc > 440ms.

5 days