Cocaine Use Disorder
Conditions
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.
Interventions
DRUGSuvorexant
The pharmacodynamic effects of suvorexant maintenance will be determined.
DRUGCocaine
The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and suvorexant.
DRUGPlacebo oral capsule
The pharmacodynamic effects of placebo will be determined.
Sponsors
National Institute on Drug Abuse (NIDA)
William Stoops
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reinforcing Effects of Cocaine | 12 times over approximately 1 month inpatient admission. | Number of Times Subjects Choose Cocaine (Maximum of 10 Choices) Over Money |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects Included in Analysis This study used a within subjects design (i.e., all subjects were to receive all oral suvorexant maintenance conditions \[0, 5, 10 and 20 mg\] and intravenous cocaine doses \[0, 10 and 30 mg/70 kg\]). Seven subjects completed the full study. An eighth was enrolled but discharged at the outset of the COVID-19 pandemic. Data from completed sessions for that subject are included here. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | COVID-19 Pandemic | 1 |
Baseline characteristics
| Characteristic | Subjects Included in Analysis |
|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Reinforcing Effects of Cocaine
Number of Times Subjects Choose Cocaine (Maximum of 10 Choices) Over Money
Time frame: 12 times over approximately 1 month inpatient admission.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Condition 1 | Reinforcing Effects of Cocaine | 1.3 Number of Cocaine Choices | Standard Error 3.5 |
| Dose Condition 2 | Reinforcing Effects of Cocaine | 5.0 Number of Cocaine Choices | Standard Error 5.3 |
| Dose Condition 3 | Reinforcing Effects of Cocaine | 8.3 Number of Cocaine Choices | — |
| Dose Condition 4 | Reinforcing Effects of Cocaine | 0 Number of Cocaine Choices | Standard Error 0 |
| Dose Condition 5 | Reinforcing Effects of Cocaine | 3.7 Number of Cocaine Choices | Standard Error 8.4 |
| Dose Condition 6 | Reinforcing Effects of Cocaine | 8.4 Number of Cocaine Choices | Standard Error 2.7 |
| Dose Condition 7 | Reinforcing Effects of Cocaine | 1.3 Number of Cocaine Choices | Standard Error 3.5 |
| Dose Condition 8 | Reinforcing Effects of Cocaine | 8.1 Number of Cocaine Choices | Standard Error 3.7 |
| Dose Condition 9 | Reinforcing Effects of Cocaine | 9.3 Number of Cocaine Choices | Standard Error 1.9 |
| Dose Condition 10 | Reinforcing Effects of Cocaine | 0.4 Number of Cocaine Choices | Standard Error 1.1 |
| Dose Condition 11 | Reinforcing Effects of Cocaine | 6.6 Number of Cocaine Choices | Standard Error 4.7 |
| Dose Condition 12 | Reinforcing Effects of Cocaine | 8.7 Number of Cocaine Choices | Standard Error 1.9 |