Interaction of Stress and Progesterone Levels on Cocaine Cue Induced Craving in Cocaine Dependent Individuals

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 GCRC 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.

- 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 GCRC 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, including SRI's or other
antidepressants, opiates or opiate antagonists because these may affect test
response.

- Subjects with any acute illness or fever. Individuals who otherwise meet study
criteria will be rescheduled for evaluation for participation.

- Subjects who are obese (20% over ideal weight) 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 or cocaine as appropriate) within the past 60 days.