The purpose of the study is to asses the potential interactions between intravenous cocaine
and doxazosin in cocaine dependent volunteers who are not seeking treatment. The study will
evaluate the effects of doxazosin on the cardiovascular and subjective effects of cocaine in
a human laboratory study.
Minimum age: 18 Years.
Maximum age: 55 Years.
- Be English-speaking volunteers who are not seeking treatment at the time of the
- Be between 18-55 years of age.
- Meet DSM-IV TR criteria for cocaine dependence; participants may or may not meet
criteria for nicotine dependence. Nicotine dependence is allowed but not required
because most cocaine users smoke cigarettes.
- Have a self-reported history of using cocaine by the smoked or IV route.
- Have vital signs as follows: supine blood pressure > 100/65 mm Hg, a seated blood
pressure of > 90/60 mm Hg and < 150/90 mm Hg, and an orthostatic change < 20 mm Hg
systolic or <10 mm Hg diastolic on standing. Resting pulse must be < 90 bpm.
- Have hematology and chemistry laboratory tests that are within normal (+/- 10%)
limits with the following exceptions: a) liver function tests (total bilirubin, ALT,
AST, and alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney
function tests (creatinine and BUN) within normal limits.
- Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically
normal conduction, and no clinically significant arrhythmias.
- Have a medical history and brief physical examination demonstrating no clinically
significant contraindications for study participation, in the judgment of the
admitting physician and the principal investigator.
- Meet DSM-IV TR criteria for dependence on drugs other than cocaine or nicotine.
- Have any history or evidence suggestive of seizure disorder or brain injury.
- Have any previous medically adverse reaction to cocaine, including loss of
consciousness, chest pain, or epileptic seizure.
- Have neurological or psychiatric disorders, such as: psychosis, bipolar illness or
major depression as assessed by MINI; organic brain disease or dementia assessed by
clinical interview; history of any psychiatric disorder which would require ongoing
treatment or which would make study compliance difficult; history of suicide attempts
within the past year and/or current suicidal ideation/plan.
- Have evidence of clinically significant heart disease or hypertension, as determined
by the PI.
- Have evidence of untreated or unstable medical illness including: neuroendocrine,
autoimmune, renal, hepatic, or active infectious disease.
- Have symptomatic HIV or are taking antiretroviral medication.
- Be pregnant or nursing. Other females must either be unable to conceive (i. e.,
surgically sterilized, sterile, or post-menopausal) or be using a reliable form of
contraception (e. g., abstinence, birth control pills, intrauterine device, condoms,
or spermicide). All females must provide negative pregnancy urine tests before study
entry, upon hospital admission, and at the end of study participation.
- Have asthma or currently use theophylline or other sympathomimetics.
- Have any other illness, condition, or use of psychotropic medications, which in the
opinion of the PI and/or the admitting physician would preclude safe and/or
successful completion of the study.
Criteria for Discontinuation Following Initiation:
Participants will be discharged if they have a positive breath test indicating use of
alcohol or a urine test indicating illicit use of drugs while in the MED-VAMC, if they do
not comply with study procedures, or if they do not tolerate the study drugs.
Subject Selection Criteria Rationale for Route of Administration:
Participants are required to have used cocaine by the IV or smoked route to avoid exposing
participants to drugs by routes of administration that produce more intensive
interoceptive effects than usually used by the participants. Prior experience with smoked
cocaine is allowed (rather than restricting the population to those with experience with
IV cocaine) because smoked cocaine reaches brain sites of action as rapidly as does
intravenously administered cocaine and smoked cocaine produces effects that are comparable
to IV cocaine. Speed of administration (and rate of delivery to brain) of stimulant drugs
likely impacts subjective and cardiovascular effects, so smoked and intravenously
administered cocaine produce similar subjective effects.