The Effect of Yohimbine on Cocaine Cue Reactivity

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.

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.