Suvorexant and Cocaine
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo 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
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.
Drug: Placebo oral capsule
The pharmacodynamic effects of placebo will be determined.
|
| Experimental: Suvorexant Dose 1 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
The pharmacodynamic effects of suvorexant maintenance will be determined.
Drug: Cocaine
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.
|
| Experimental: Suvorexant Dose 2 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
The pharmacodynamic effects of suvorexant maintenance will be determined.
Drug: Cocaine
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.
|
| Experimental: Suvorexant Dose 3 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
The pharmacodynamic effects of suvorexant maintenance will be determined.
Drug: Cocaine
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.
|
Outcome Measures
Primary Outcome Measures
- Reinforcing Effects of Cocaine Following Placebo Maintenance. [Following at least 3 days of maintenance on placebo during inpatient admission]
Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
- Reinforcing Effects of Cocaine Following Suvorexant Dose 1 Maintenance. [Following at least 3 days of maintenance on suvorexant dose 1 during inpatient admission]
Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
- Reinforcing Effects of Cocaine Following Suvorexant Dose 2 Maintenance. [Following at least 3 days of maintenance on suvorexant dose 2 during inpatient admission]
Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
- Reinforcing Effects of Cocaine Following Suvorexant Dose 3 Maintenance. [Following at least 3 days of maintenance on suvorexant dose 3 during inpatient admission]
Number of cocaine doses earned by subjects on a progressive ratio schedule of reinforcement.
Secondary Outcome Measures
- Adjective Rating Scale-Sedative [12 times over approximately 1 month inpatient admission]
Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale.
- Adjective Rating Scale-Stimulant [12 times over approximately 1 month inpatient admission]
Subjects will complete the adjective rating scale during 12 sessions while they are admitted to our inpatient unit. Responses to 16 items are summed (total score=0-64; Higher values=more sedation) to calculate scores on a sedative subscale.
- Drug Effect Questionnaire [12 times over approximately 1 month inpatient admission]
Subjects will complete the drug effect questionnaire during 12 sessions while they are admitted to our inpatient unit. The items (total scores=0-100; Higher scores=greater drug effect) on this scale categorize the constellation of drug effects endorsed by subjects.
- Heart rate [Daily over approximately four week inpatient admissions]
Beats per minute. Measured daily during inpatient admission.
- Blood pressure [Daily over approximately 1 month inpatient admissions]
mmHg. Measured daily during inpatient admission.
- Temperature [Daily over approximately 1 month inpatient admissions]
Degrees fahrenheit. Measured daily during inpatient admission.
- Side Effects [Daily over approximately 1 month inpatient admissions]
Subjects will complete a side effects questionnaire daily while they reside on the inpatient unit. Side Effects questions will query subjects about common effects of centrally active medications.
- Delay Discounting Task [12 times over approximately 1 month inpatient admission.]
Subjects will complete the delay discounting task during 12 sessions while they are admitted to our inpatient unit. Responses will be used to calculate discounting slope (i.e., K).
- Attentional Bias [12 times over approximately 1 month inpatient admission.]
Subjects will complete attentional bias during 12 sessions while they are admitted to our inpatient unit. Time attending to drug stimuli will be used to evaluate attentional bias.
- Sleep [Daily over approximately 1 month inpatient admissions]
Subjects will complete a sleep questionnaire daily while they reside on the inpatient unit.
Eligibility Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Kentucky | Lexington | Kentucky | United States | 40507 |
Sponsors and Collaborators
- William Stoops
- National Institute on Drug Abuse (NIDA)
Investigators
- Principal Investigator: William W Stoops, PhD, University of Kentucky
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BED IN 39