The goal of this clinical trial is to learn if Cobenfy influences the effects of cocaine in people with cocaine use disorder. This trial will also provide information about the safety and tolerability of combining Cobenfy and cocaine.

Researchers will compare Cobenfy to a placebo (a look-alike substance that contains no drug) to see if Cobenfy is a safe, tolerable and effective at blocking cocaine's effects in participants with cocaine use disorder.

Participants will:

• Participate in an 11-day inpatient trial
• Take Cobenfy or placebo twice per day.
• Participate in experimental sessions to test the effects of Cobenfy (or placebo) on the response to cocaine and cocaine self-administration.

Inclusion Criteria:

• Must meet criteria for cocaine use disorder - report past month smoked or IV cocaine use, and provide a urine sample positive for recent cocaine use during screening.
• Female subjects of childbearing potential must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, IUD, cervical cap with a spermicide, or abstinence). Exceptions include women reporting 12 months of spontaneous amenorrhea, 6 months of spontaneous amenorrhea with a follicle stimulating hormone (FSH) level > 40 mIU/mL, or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy. Urine pregnancy tests will be conducted prior to sessions to ensure that female subjects do not participate if pregnant.
• Able to speak and read English.

Exclusion Criteria:

• Chemistry values or screening outcomes including outside normal ranges that are deemed by the study physician to be clinically significant. Lipid levels are also included in this protocol as an additional check for cardiovascular health.
• Persistent hypertension >140/90 mmHg or tachycardia >100 bpm for three consecutive recordings during screening.
• AST, ALT or alkaline phosphatase >3x ULN.
• Creatinine levels >1.2x ULN will be repeated; subjects with creatinine re-test values remaining above this level will be excluded.
• Bilirubin levels >1.5x ULN will be repeated to determine trends; subjects with bilirubin increasing over time will be excluded.
• Subjects presenting with anemia (hematocrit < 36) or evidence of current infection (white blood cell count > 5) are referred to their PCP. If urine protein is greater than trace, urinalysis is repeated, and subjects with continued elevation is referred to their PCP. Subjects can be reconsidered for enrollment if these issues are resolved.
• Electrocardiogram abnormalities, including:
• Atrial premature beats (>= 2 consecutive)
• Ventricular premature beats (Lown's Grade 3 or higher; >= 2 consecutive beats, multiform)
• Heart block (2nd or 3rd degree AV block or bundle branch block)
• Pre-excitation syndromes (Wolff-Parkinson-White or Lown-Ganong-Levine)
• QTc interval > 450 msec
• History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of head trauma with prolonged loss of consciousness, seizures or CNS tumors, or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation.
• First degree family member with significant premature cardiac comorbidity.
• Contraindications for Cobenfy not covered by other exclusion criteria including urinary retention, moderate/severe hepatic impairment, gastric retention and untreated narrow-angle glaucoma.
• Meet diagnostic criteria for psychoactive substance use disorder for substances other than cocaine or nicotine/caffeine that would require detoxification (i.e., alcohol, opioids, benzodiazepines or barbiturates). Negative urine/breath samples for these substances, and the absence of withdrawal, will be required during screening.
• Regular use of other medications, with the exception of hormone-based contraceptives for female subjects, daily multivitamins, short-term antibiotic prescriptions, and/or antiretrovirals for the hepatitis C virus.
• Vision or hearing problems that would preclude completion of experimental tasks.
• Poor venous access.
• Seeking treatment for SUD.