Modafinil is a medication that may enhance mood and increase energy in cocaine addicts,
which may be useful in preventing cocaine relapse. Naltrexone is a medication that is
currently used to treat drug and alcohol addiction. A combination of these two medications
may be beneficial in reducing drug and alcohol use in individuals undergoing substance abuse
treatment. The purpose of this study is to evaluate the effectiveness of modafinil and
naltrexone, alone and in combination, at reducing drug and alcohol use in individuals
addicted to cocaine and alcohol.
Cocaine and alcohol addiction are serious health problems with no available medical
treatment for preventing relapse. Past research has shown that individuals who are addicted
to both cocaine and alcohol typically respond poorly to conventional substance abuse
treatment. Little attention has been directed towards how best to treat these individuals.
Naltrexone is a medication that is currently used to treat drug and alcohol addiction. It
acts by blocking the "high" feeling produced by drugs and alcohol. Modafinil, another
medication, enhances mood, increases energy, and improves concentration in people with
narcolepsy. Preliminary research has shown that it may produce similar effects to cocaine,
thereby potentially countering the symptoms of cocaine withdrawal. Cognitive Behavioral
Coping Skills Therapy (CBT), a form of therapy that aims to alter an individual's patterns
of behavior and drug use, is also an important component of substance abuse treatment. The
purpose of this study is to compare the effectiveness of CBT plus placebo, CBT plus
modafinil, CBT plus naltrexone, and CBT plus a combination of modafinil and naltrexone at
reducing cocaine and alcohol use in individuals addicted to both substances.
This 14-week study will enroll individuals addicted to both cocaine and alcohol. During a
1-week screening period, potential participants will be required to complete a
detoxification program, including stopping all cocaine and alcohol use. Participants will
also undergo a physical exam and an electrocardiogram. Blood will be drawn for laboratory
tests, and urine tests will be used to screen for the presence of drugs and alcohol.
Individuals who complete the screening and meet all study requirements will be permitted to
participate in the treatment phase of the study. During the 13-week treatment phase,
participants will be randomly assigned to receive modafinil, naltrexone, a combination of
modafinil and naltrexone, or placebo. All participants will attend a CBT session once a
week. Study visits will take place twice a week. At each visit, a urine test and
breathalyzer will be used to screen for the presence of alcohol and drugs. Participants will
also complete standardized psychological questionnaires to measure drug and alcohol craving,
treatment services received, severity of illness, and withdrawal symptoms. In addition,
participants will meet weekly with a nurse practitioner, who will dispense study
medications, monitor adverse events, and evaluate the participant's clinical status. A
follow-up evaluation will occur 6 months following the end of treatment.
4.1 Inclusion Criteria
1. Male and females, 18 years of age or older.
2. Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence,
determined by the SCID-IV.
3. In the past 30 days, used no less than $200-worth of cocaine and meets the following
drinking criteria as measured by the Timeline Followback (TLFB) (Sobell, 1995):
1. drank within 30 days of intake day,
2. reports a minimum of 48 standard alcoholic (avg. 12 drinks/wk) in a consecutive
30-day period over the 90-day period prior to starting intake (i.e., a minimum
of 40% days drinking), and
3. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in
males and 4 or more drinks per day in females) in this same pre-treatment
4. 72 consecutive hours of abstinence from alcohol, determined by self-reports and
confirmed by a negative breathalyzer tests, and a Clinical Institute Withdrawal Scale
for Alcohol (CIWA-AR) (Sullivan, 1989) score below eight. Subjects will be
encouraged to achieve 72 consecutive hours of abstinence, however, subjects who have
achieved between 48 and 72 consecutive hours of abstinence will be included with the
approval of the principal investigator. We anticipate that these subjects will
comprise less than 5% of total enrolled subjects. Subjects will be given 2
additional weeks beyond the screening week to attain the appropriate period of
alcohol abstinence prior to randomization.
5. Lives a commutable distance from the TRC and agrees to attend all research visits
including follow-up visits.
6. Speaks, understands, and prints in English
7. Ability to give informed consent
1. Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent
2. Meets DSM IV criteria for dependence on any substance other than cocaine and alcohol
(except nicotine), determined by the SCID.
3. Needs treatment with any psychoactive medications including any anti-seizure
medications (with the exception of diphenhydramine used sparingly, if necessary, for
4. Meets current or lifetime DSM-IV criteria for schizophrenia or any psychotic disorder
or organic mental disorder. Subject meets current DSM-IV diagnosis of any other
clinically significant psychiatric disorder that will interfere with study
5. Has evidence of a history of significant hematological, pulmonary, endocrine,
cardiovascular, renal or gastrointestinal disease (including a history of myocardial
infarction, mitral valve prolapse, left ventricular hypertrophy, uncontrolled
6. Severe physical or medical illnesses such as AIDS, active hepatitis, significant
hepatocellular injury as evidenced by elevated total bilirubin levels (>1.3 mg/dl),or
elevated levels (over 4.5x normal) of aspartate aminotransferase (AST), and serum
glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence.
7. Use of an investigational medication in the 30 days prior to randomization.
8. History of hypersensitivity to modafinil or naltrexone
9. Receiving chronic therapy with any drug known to interact adversely with either
modafinil or naltrexone including propranolol, phenytoin, warfarin, diazepam
10. Took a monoamine oxidase inhibitor within 30 days of randomization.
11. Is female and tests positive on a pregnancy test, is contemplating pregnancy in the
next 6 months, is nursing, or is not using an effective contraceptive method (if
relevant). Acceptable methods of contraception include barrier methods (diaphragm or
condom with spermicide, female condom), intrauterine progesterone contraceptive
system, levonorgrestrel implant, and medroxyprogeterone acetate contraceptive
injection, copper IUD, vaginal contraceptive film, cervical cap, contraceptive foam.
12. Current use of an oral contraceptive without other acceptable barrier method of
13. Received therapy with any opiate substitute (methadone, LAAM, buprenorphine) within
60 days of randomization