Suvorexant and Cocaine

Study Overview
=================
Brief Summary
-----------------
The research proposed here will translate findings from preclinical research and provide the initial clinical evidence that orexin antagonism reduces motivation for cocaine, as well as other cocaine-associated maladaptive behaviors in active cocaine users. This study will also provide basic science information about the orexinergic mechanisms underlying the pharmacodynamic effects of cocaine in humans. As such the outcomes will contribute to our understanding of the clinical neurobiology of cocaine use disorder. Overall, the proposed work seeks to expand the scope of current clinical neuroscience research on cocaine addiction by focusing on orexin, which has strong preclinical evidence supporting its critical role in addiction but remains unstudied in humans.

Official Title
-----------------
Influence of Orexin Antagonism on Motivation for Cocaine

Conditions
-----------------
Cocaine Use Disorder

Intervention / Treatment
-----------------
* Drug: Suvorexant
* Drug: Cocaine
* Drug: Placebo oral capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recent 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, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation Females not currently using effective birth control Contraindications to cocaine, methylphenidate or duloxetine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will be maintained on oral placebo. Cocaine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance. | Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.<br>Drug: Placebo oral capsule<br>* The pharmacodynamic effects of placebo will be determined.<br>|
| Experimental: Suvorexant Dose 1<br>Subjects will be maintained on oral suvorexant dose 1. Cocaine will be administered acutely during suvorexant dose 1 maintenance. Placebo will be administered acutely during suvorexant dose 1 maintenance. | Drug: Suvorexant<br>* The pharmacodynamic effects of suvorexant maintenance will be determined.<br>Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.<br>|
| Experimental: Suvorexant Dose 2<br>Subjects will be maintained on oral suvorexant dose 2. Cocaine will be administered acutely during suvorexant dose 2 maintenance. Placebo will be administered acutely during suvorexant dose 2 maintenance. | Drug: Suvorexant<br>* The pharmacodynamic effects of suvorexant maintenance will be determined.<br>Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.<br>|
| Experimental: Suvorexant Dose 3<br>Subjects will be maintained on oral suvorexant dose 3. Cocaine will be administered acutely during suvorexant dose 3 maintenance. Placebo will be administered acutely during suvorexant dose 3 maintenance. | Drug: Suvorexant<br>* The pharmacodynamic effects of suvorexant maintenance will be determined.<br>Drug: Cocaine<br>* The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reinforcing Effects of Cocaine | Number of Times Subjects Choose Cocaine (Maximum of 10 Choices) Over Money | 12 times over approximately 1 month inpatient admission. |