The Effect of Yohimbine on Cocaine Cue Reactivity

This study has been completed.
Sponsor:
Collaborators:
Information provided by:
Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00535002
First received: September 21, 2007
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

Stress and cues reminiscent of cocaine use promote craving and relapse in cocaine dependent individuals. In addition, there appears to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Therefore the purpose of the present study is to study the role of hormonal status on the response to cocaine-related cues with or without stress in cocaine-dependent women and men.


Condition Intervention
Cocaine Related Disorders
Drug: Yohimbine
Drug: Placebo

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: SCOR on Sex and Gender Factors Affecting Women's Health

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Cocaine craving [ Time Frame: Post cocaine cue exposure ] [ Designated as safety issue: No ]
    Cocaine-dependent participants were pre-treated with either yohimbine or placebo provided subjective ratings of cocaine craving immediately following cocaine cue exposure.


Biospecimen Retention:   Samples With DNA

whole blood saliva


Enrollment: 113
Study Start Date: September 2007
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
non-dependent males
Drug: Yohimbine
Participants were pre-treated with either yohimbine or placebo.
Drug: Placebo
2
non-dependent females
Drug: Yohimbine
Participants were pre-treated with either yohimbine or placebo.
Drug: Placebo
3
cocaine dependent males
Drug: Yohimbine
Participants were pre-treated with either yohimbine or placebo.
Drug: Placebo
4
cocaine dependent females
Drug: Yohimbine
Participants were pre-treated with either yohimbine or placebo.
Drug: Placebo

Detailed Description:

Cocaine dependence is an insidious disease underscored by a strong propensity to relapse despite knowledge of the repercussions of continued drug-use. Stress and cocaine cues produce craving and ultimately relapse in cocaine dependent individuals. Pre-clinical research has demonstrated sex differences in response to cocaine-conditioned cues and cocaine-primed reinstatement, which correlates well with reduced plasma progesterone levels. Interestingly, this is consistent with a growing body of clinical literature indicating that progesterone may decrease the reinforcing properties of stimulants in women. Gender differences in the response to a social stressor and cocaine cues in cocaine-dependent individuals have been demonstrated in human laboratory studies, however, the interaction of stress and cues and the effect of hormonal status on response have not been explored. This study examines the role of hormonal status on the response to cocaine-related cues with or without a pharmacological stressor (yohimbine) in cocaine-dependent women and men. As a further integration of the research focus this study also explores the relationship between impulsivity and craving.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The study population will include subjects meeting diagnostic criteria for current cocaine dependence (DSM-IV). Subjects will be recruited through local media advertisements (newspaper, radio, and television), the Institute of Psychiatry Center for Drug and Alcohol Programs, the Charleston Center, the Ralph H. Johnson VA Medical Center, and the Dorchester Alcohol and Drug Commission. Women will be included in the study. In our previous studies, approximately 50% of subjects have been female. African Americans will be recruited into the protocol. Charleston's population is 64% Caucasian, 35% African American and 2% Other. In a previous study, 59% of the subjects were women, 36% were White, 62% African American, and 2% Other, and expect that the racial spectrum will be similar.

Criteria

Inclusion Criteria:

  • Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
  • Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for a three-day period immediately prior to the CTRC admission. Nicotine dependence can affect HPA function (Baron et al., 1995) therefore it would be ideal to exclude subjects with nicotine use. Because of the high comorbidity of cocaine and nicotine dependence, this would seriously compromise the feasibility of recruitment. Individuals with alcohol dependence will be excluded. However because of the high comorbidity of alcohol use and cocaine dependence, individuals with alcohol abuse will be included. 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.
  • Subjects with ADHD will be included. Because ADHD is commonly characterized by impulsivity, ADHD severity ratings will be determined and controlled for in data analysis.
  • Subjects must consent to random assignment.
  • Subjects must consent to outpatient admission to the CTRC and two overnight admissions to the Medical University Hospital.

Exclusion Criteria:

  • Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
  • Women with premenstrual dysphoric disorder as this may impact on the response to the stress test procedure (Woods et al., 1994).
  • Women receiving depot medroxyprogesterone acetate as a form of birth control.
  • 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.
  • Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect hormonal/neuroendocrine status.
  • Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with subjective measurements.
  • Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in stress response.
  • Subjects with panic disorder, as yohimbine may precipitate panic attacks.
  • 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.
  • Subjects taking any psychotropic medications,antidepressants, opiates or opiate antagonists because these may affect test response. Subjects taking SSRI's will be included.
  • Subjects with any acute illness or fever. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation.
  • Subjects who are obese (BMI>35) as this may interfere with hormonal status.
  • 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.
  • Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, alcohol, marijuana or cocaine as appropriate) within the past 60 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00535002

Locations
United States, South Carolina
Medical University of South Carolina-GCRC
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Kathleen T Brady, M.D., Ph.D. Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Kathleen Brady MD PhD, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00535002     History of Changes
Other Study ID Numbers: P50DA016511-1, P50DA016511
Study First Received: September 21, 2007
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Medical University of South Carolina:
Cocaine Addiction
Cocaine Dependence

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Yohimbine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Mydriatics
Autonomic Agents
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Urological Agents

ClinicalTrials.gov processed this record on August 27, 2014