Cocaine Dependence
Conditions
Keywords
cocaine, substance abuse, drug abuse, cocaine dependence, drug addiction
Brief summary
Stress is likely involved in relapse to cocaine use. This project will investigate the role oxytocin may play in the stress response in cocaine-dependent men and women and examine how oxytocin may impact brain activity in individuals exposed to cocaine-related cues.
Detailed description
Stress is an important predictor of relapse, and targeting stress-activated pathways may lead to therapeutic advancements in the treatment of substance use disorders. Oxytocin has been shown to promote trust, social bonding, and calmness; however, its potential effects have not been explored in cocaine-dependent individuals. Oxytocin receptors have been localized to brain regions that are activated by drug-paired cues and preclinical studies have shown that oxytocin attenuates the acute and long-term behavioral effects of psychostimulants. However, little is known about the role of oxytocin in mediating the affective response to cocaine-paired cues and associated neural activity in cocaine-dependent men and women. This project is a direct evolution from our previous SCOR-supported research. Our work has progressed from characterizing sex/gender differences in response to social stressors and cocaine cues in cocaine-dependent men and women, to our on-going work evaluating whether stress potentiates cue-induced craving and the impact of hormones on this response. The proposed study will investigate the role of oxytocin in the sex/gender differences in stress response and craving in cocaine-dependent individuals and preliminarily explore its therapeutic potential.
Interventions
DRUGOxytocin
intranasal administration, 40 IUs
DRUGSaline
intranasal administration, 40 IUs
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. 2. Subjects must meet DSM-IV criteria for current cocaine dependence (within the past three months). While individuals may also meet criteria for abuse of other substances, they must not meet criteria for dependence on any other substance (except nicotine) within the last 60 days. Alcohol has been known to affect HPA function (Adinoff et al., 1991), however to enhance recruitment efforts individuals with alcohol dependence or abuse will be included in the study if they do not require medically supervised detoxification. Also, due to the high comorbidity of cocaine and marijuana dependence, and limited evidence that marijuana use affects HPA function, subjects with marijuana dependence will be included. 3. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the throughout study procedures. 4. Subjects must consent to random assignment. 5. Subjects must consent to participating in study procedures at the ASD and completion of two fMRI scans.
Exclusion criteria
1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control (not including hormonal contraceptives). 2. Women who are currently taking, or have taken in the past month, oral or other types of hormonal contraceptives or hormone replacement therapies. 3. Women with premenstrual dysphoric disorder who are outside of the follicular phase. 4. Women who have had a complete hysterectomy or are over 50 over one year post-menopausal, as ovarian hormones will be measured in the study. 5. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect physiological/subjective responses. Neurological exclusions include history of stroke, seizure disorders, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. 6. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status. 7. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements. 8. Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response. 9. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with hormonal measurements within one month of test session. 10. Subjects taking any mood stabilizers, antipsychotics, benzodiazepines, opiates or opiate antagonists because these may affect test response. Subjects taking SSRI's will be included. 11. Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation. 12. Subjects whose height to weight ratio would preclude them from fitting comfortably in the MRI scanner. 13. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) for three days prior to the stress task procedure. 14. Persons with ferrous metal implants or pacemaker since fMRI will be used. 15. Subjects who are claustrophobic. 16. Subjects with significant psychiatric or medical problems that would impair participation or limit ability to participate in scan. 17. Subjects who require maintenance or acute treatment with any psychoactive medication including anti-seizure medications which could potentially interfere with fMRI. 18. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, cocaine, alcohol or marijuana) within the past 60 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Stress Response TSST | Subjects rated stress immediately following a Social Stress task on Day 1 of 3. | Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels. |
| Subjective Stress Response MRI 1 | Subjects rated Stress immediately following the first of two MRI scans on Day 2 of 3. | Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels |
| Subjective Stress Response MRI 2 | Subjects rated stress immediately following the second of two MRI scans on Day 3 of 3. | Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Cocaine Craving TSST | Subjects rated craving immediately following a Social Stress task on Day 1 of 3. | Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving. |
| Subject Cocaine Craving MRI 1 | Subjects rated craving immediately following the first of two MRI scans on Day 2 of 3. | Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving. |
| Subject Cocaine Craving MRI 2 | Subjects rated craving immediately following the second of two MRI scans on Day 3 of 3. | Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving. |
Countries
United States
Participant flow
Pre-assignment details
112 is the total number of participants randomized. 112 completed the TSST, which was between groups. MRIs were within subjects; 99 completed at least MRI 1. 96 completed MRI's 1 and 2. Data is reported per testing condition.
Participants by arm
| Arm | Count |
|---|---|
| Cocaine- Dependent Women Oxytocin Cocaine-dependent women received 40 IUs of intranasal oxytocin prior to completing a Social Stress Task on Day 1, and MRI on Day 2 and an MRI on Day 3. The TSST task was between subjects; the MRI tasks were within subjects. | 24 |
| Cocaine- Dependent Men Oxytocin Cocaine-dependent men received 40 IUs of intranasal oxytocin prior to completing a Social Stress Task on Day 1, and MRI on Day 2 and an MRI on Day 3. The TSST task was between subjects; the MRI tasks were within subjects. | 32 |
| Cocaine- Dependent Women Placebo Cocaine-dependent women received Placebo prior to completing a Social Stress Task on Day 1, and MRI on Day 2 and an MRI on Day 3. The TSST task was between subjects; the MRI tasks were within subjects. | 25 |
| Cocaine -Dependent Men Placebo Cocaine-dependent men received Placebo prior to completing a Social Stress Task on Day 1, an MRI on Day 2 and an MRI on Day 3. The TSST task was between subjects; the MRI tasks were within subjects. | 31 |
| Total | 112 |
Baseline characteristics
| Characteristic | Cocaine- Dependent Women Oxytocin | Cocaine- Dependent Men Oxytocin | Cocaine- Dependent Women Placebo | Cocaine -Dependent Men Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 32 Participants | 25 Participants | 31 Participants | 112 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 24 Participants | 13 Participants | 24 Participants | 79 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 11 Participants | 7 Participants | 32 Participants |
| Region of Enrollment United States | 24 participants | 32 participants | 25 participants | 31 participants | 112 participants |
| Sex: Female, Male Female | 24 Participants | 0 Participants | 25 Participants | 0 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 32 Participants | 0 Participants | 31 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 | 0 / 19 | 0 / 23 | 0 / 23 | 0 / 18 | 0 / 32 | 0 / 31 | 0 / 28 | 0 / 29 | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 0 / 24 | 0 / 25 | 0 / 19 | 0 / 23 | 0 / 23 | 0 / 18 | 0 / 32 | 0 / 31 | 0 / 28 | 0 / 29 | 0 / 27 | 0 / 28 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 | 0 / 19 | 0 / 23 | 0 / 23 | 0 / 18 | 0 / 32 | 0 / 31 | 0 / 28 | 0 / 29 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Subjective Stress Response MRI 1
Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels
Time frame: Subjects rated Stress immediately following the first of two MRI scans on Day 2 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subjective Stress Response MRI 1 | 2.05 units on a scale | Standard Deviation 2.34 |
| TSST Women Placebo | Subjective Stress Response MRI 1 | 2.13 units on a scale | Standard Deviation 2.87 |
| TSST Men Oxytocin | Subjective Stress Response MRI 1 | 1.75 units on a scale | Standard Deviation 2.4 |
| TSST Men Placebo | Subjective Stress Response MRI 1 | 2.66 units on a scale | Standard Deviation 2.84 |
Primary
Subjective Stress Response MRI 2
Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels.
Time frame: Subjects rated stress immediately following the second of two MRI scans on Day 3 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subjective Stress Response MRI 2 | 0.83 units on a scale | Standard Deviation 1.67 |
| TSST Women Placebo | Subjective Stress Response MRI 2 | 1.83 units on a scale | Standard Deviation 2.81 |
| TSST Men Oxytocin | Subjective Stress Response MRI 2 | 1.07 units on a scale | Standard Deviation 2.07 |
| TSST Men Placebo | Subjective Stress Response MRI 2 | 1.39 units on a scale | Standard Deviation 2.06 |
Primary
Subjective Stress Response TSST
Subjects rated stress levels on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower stress levels.
Time frame: Subjects rated stress immediately following a Social Stress task on Day 1 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subjective Stress Response TSST | 5.33 units on a scale | Standard Deviation 3.81 |
| TSST Women Placebo | Subjective Stress Response TSST | 5.28 units on a scale | Standard Deviation 4.09 |
| TSST Men Oxytocin | Subjective Stress Response TSST | 2.05 units on a scale | Standard Deviation 2.34 |
| TSST Men Placebo | Subjective Stress Response TSST | 2.13 units on a scale | Standard Deviation 2.87 |
Secondary
Subject Cocaine Craving MRI 1
Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving.
Time frame: Subjects rated craving immediately following the first of two MRI scans on Day 2 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subject Cocaine Craving MRI 1 | 2.89 units on a scale | Standard Deviation 3.31 |
| TSST Women Placebo | Subject Cocaine Craving MRI 1 | 2.65 units on a scale | Standard Deviation 2.81 |
| TSST Men Oxytocin | Subject Cocaine Craving MRI 1 | 3.04 units on a scale | Standard Deviation 2.7 |
| TSST Men Placebo | Subject Cocaine Craving MRI 1 | 3.69 units on a scale | Standard Deviation 2.99 |
Secondary
Subject Cocaine Craving MRI 2
Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving.
Time frame: Subjects rated craving immediately following the second of two MRI scans on Day 3 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subject Cocaine Craving MRI 2 | 2.17 units on a scale | Standard Deviation 2.7 |
| TSST Women Placebo | Subject Cocaine Craving MRI 2 | 2.61 units on a scale | Standard Deviation 2.78 |
| TSST Men Oxytocin | Subject Cocaine Craving MRI 2 | 2.04 units on a scale | Standard Deviation 2.38 |
| TSST Men Placebo | Subject Cocaine Craving MRI 2 | 2.29 units on a scale | Standard Deviation 2.54 |
Secondary
Subject Cocaine Craving TSST
Subjects rated craving on a 0-10 Likert Scale where 0 is Not at All and 10 is Extremely so that lower scores indicate lower craving.
Time frame: Subjects rated craving immediately following a Social Stress task on Day 1 of 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TSST Women Oxytocin | Subject Cocaine Craving TSST | 3.08 units on a scale | Standard Deviation 3.69 |
| TSST Women Placebo | Subject Cocaine Craving TSST | 3.24 units on a scale | Standard Deviation 3.38 |
| TSST Men Oxytocin | Subject Cocaine Craving TSST | 3.45 units on a scale | Standard Deviation 3.35 |
| TSST Men Placebo | Subject Cocaine Craving TSST | 3.45 units on a scale | Standard Deviation 3.35 |