Progesterone for the Treatment of Cocaine Dependence - 1

Changes in ovarian hormones across the menstrual cycle impact responses to cocaine in women.
Studies have shown that cocaine's effects are dampened during the luteal phase of the
menstrual cycle, when estrogen and progesterone concentrations are high, relative to the
other phases of the cycle, when concentrations of these hormones are relatively low. The
purpose of this study is to determine whether progesterone reduces subjective and
physiological responses to cocaine in cocaine dependent individuals. In addition, this study
will help to advance the possibility of hormonal progesterone and pharmacologically related
drugs as potential treatment components for cocaine abuse.

Participants will undergo two 4-day inpatient periods, totaling 8 days of treatment. For
women, the inpatient periods will occur during two consecutive menstrual cycles; for men,
they will occur during two consecutive months. On Day 1, participants will receive a first
dose of either progesterone or placebo. On Day 2, participants will receive a second and
third dose of study medication. They will also participate in an adaptation session, which
will familiarize the participant with the smoking equipment that will be used the following
day. On Day 3, participants will receive a fourth dose of medication 2 hours prior to a
smoking lab session. Prior to beginning the smoking lab session, participants will be asked
to rate their current cocaine craving, anxiety level, appetite, and premenstrual symptoms.
Participants will then be given a sample of the cocaine dose for the given day. During the
smoking lab session, participants will be asked additional cocaine craving questions at
pre-determined intervals and will be given the option to trade in previously earned tokens
for either money or a dose of cocaine. Following completion of the smoking lab session,
participants will receive their fifth dose of medication.

Inclusion Criteria:

- Smoked at least 1 gram of cocaine each week for the 6 months prior to study entry

- Agrees to use an adequate method of contraception for the duration of the study

- If female, current regular menses

Exclusion Criteria:

- Major psychiatric illnesses, including psychotic mood and anxiety disorders

- Current dependence on alcohol or drugs other that cocaine or nicotine

- History of major medical illnesses, including liver disease, abnormal vaginal
bleeding, suspected or known breast cancer, thrombophlebitis, or other medical
conditions

- Current use of oral contraceptives or other types of hormonal contraceptives

- Amenorrhea

- Currently on parole or probation

- Received treatment for chemical dependency within the 6 months prior to study entry

- Known allergy to progesterone or peanuts