Effects of Phenytoin on Cocaine Use in Humans - 2

The purpose of this study was to determine the effects of phenytoin on smoked cocaine-base
self-administration using our laboratory self-administration model. A total of 12 patients
randomized, 6 to phenytoin and 6 to placebo treatment group. There were 2 phases in this
10-day inpatient study. Phase 1 subjects underwent one cocaine self-admin session.
Randomization took place at the start of Phase 2, Day 4 where subjects received either
placebo or phenytoin. The subjects assigned to phenytoin treatment received an oral loading
dose (20mg/kg) aimed at achieving plasma phenytoin concentration of (10-20 mg/L). During
Phase 2, subjects had the opportunity to self-administer cocaine on Days 5, 7, and 9. The
plasma phenytoin levels were expected to decrease gradually during Phase 2 which provided an
opportunity to study the effect of decreasing phenytoin plasma concentrations on cocaine
self-administration.

Inclusion Criteria:

Males/Females between the ages of 20-40. History of smoked cocaine use on the avg. of at
least 2 times/week over a 6 month period. Have currently used at least 1 g of cocaine
within a 4-6 hr period. Current history of good health, normal serum albumin levels and
normal QTc intervals. Nonreactive for HIV. No participation in any of our studies for the
past 6 months. For females: not pregnant as determined by pregnancy screening nor breat
feeding, and using acceptable birth control methods (e.g. birth control pills, diaphragm,
condoms plus foam).

Exclusion Criteria:

History of suicide attempt, bipolar disorder, schizophrenia, or generalized anxiety
disorder. Current problem with major depressive disorder. Current use of alcohol or other
durgs on a daily basis. History of major medical illnesses. Currently on parole, probation
or a legal history of violence. Treated for chemical dependency within the past 6 months.
Use of any psychotropic drugs including MAOIs in the past 6 months.