Drug Interaction and Subjective Effects of Compounds for Opioid Use Disorder

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 65 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, or nicotine. Diagnosis of mild to moderate use disorder for
alcohol will not be considered exclusionary.

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.

16. Limited English proficiency.

17. Individuals which IV injection is their primary route of use for heroin, and may be at
increased risk for withdrawal during their inpatient visits at the CRSU