Naltrexone for Heavy Drinking in Young Adults

NIAAA has designated underage drinking as a priority research area. Of note, the highest
prevalence of problem alcohol use is among young adults ages 18-25. Heavy drinking that
occurs during this period can have important immediate and lifelong adverse consequences.
Behavioral interventions, notably BASICS (Brief Alcohol Screening and Intervention for
College Students), have been developed to help young adults reduce their drinking. Although
these interventions are effective, including with college students mandated to treatment and
others with minimal motivation to stop drinking, the effect sizes are modest, suggesting that
new approaches are needed to enhance these interventions. A promising strategy yet to be
tested in young adults is the use of the opiate antagonist naltrexone. In other research,
naltrexone has been shown to reduce the amount of alcohol consumed, even in the absence of
strong internal motivation to change, and to reduce the frequency of any and heavy drinking
in problem drinkers seeking treatment. Thus we propose to conduct an 8 week double-blind
placebo-controlled trial to test the combined efficacy of BASICS + naltrexone in 132 young
adults aged 18-25 who drink heavily. A novel strategy will be used for administering low-dose
naltrexone, in which daily dosing will be combined with targeted dosing in anticipation of
high-risk situations. The main hypotheses are that daily + targeted naltrexone will result in
greater reductions in frequency of heavy and any drinking compared with daily + targeted
placebo. In order to enhance the sensitivity with which we are able to assess naltrexone's
effects on drinking, daily ratings will be obtained during treatment. These will permit us to
examine alternative measures of alcohol involvement (e.g., reports of subjective
intoxication, estimated blood alcohol levels) in addition to the traditional measures based
on number of drinks consumed. These data will also be used to examine potential mediators
(e.g., craving, subjective effects of alcohol) of treatment response in order to better
understand the effects of naltrexone. The durability of treatment effects will be examined at
3, 6 and 12 months after randomization. Demonstration of the efficacy of naltrexone in this
population will provide the essential information needed for its adoption by college
counseling centers and other health care settings committed to reducing the risk of heavy
drinking in young adults.

Inclusion Criteria:

Each subject must:

1. Be between the ages of 18 and 25;

2. Report heavy drinking 4 or more times in the past 4 weeks. Heavy drinking is defined
as 4 or more drinks for women and 5 or more drinks for men on an occasion;

3. Be able to read English and show no evidence of significant cognitive impairment.

4. That women of child-bearing potential (i.e., who has not had a hysterectomy, bilateral
oophorectomy, or tubal ligation), be nonlactating, practicing a reliable method of
birth control, and have a negative urine pregnancy test prior to initiation of
treatment.

Exclusion Criteria:

No subject may:

1. Exhibit current, clinically significant physical disease or abnormality on the basis
of medical history, physical examination, or routine laboratory evaluation, including
AST or ALT levels greater than 3 times normal or bilirubin levels greater than 110% of
normal. Individuals with common medical conditions (e.g., asthma, diabetes mellitus,
thyroid disease) that are adequately controlled and who have a relationship with a
primary-care practitioner will not be excluded;

2. Exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe
major depression, panic disorder, borderline personality disorder, organic mood or
mental disorders, or substantial suicide or violence risk) by history or psychological
examination;

3. Have a current diagnosis of DSM-IV drug dependence other than nicotine, or a lifetime
history of DSM-IV opiate dependence;

4. Have a current DSM-IV diagnosis of alcohol dependence that is clinically severe
defined by a) a history of seizures, delirium, or hallucinations during alcohol
withdrawal, b) a Clinical Institute Withdrawal Assessment scale (Sullivan et al.,
1989) score of > 8, c) report drinking to avoid withdrawal symptoms, or d) have had
prior treatment of withdrawal.

5. Have used opioids or concomitant therapy with any psychotropic drug in the past month,
except that subjects who are on a stable dose of a Selective Serotonin Reuptake
Inhibitor for at least two months for the indications of Major Depressive Disorder,
Premenstrual Syndrome (PMS), or Premenstrual Dysphoric Disorder (PMDD) will not be
excluded; SSRIs are allowed due to their safety profile relative to other classes of
antidepressants.

6. Have a history of hypersensitivity to naltrexone;

7. Be considered by the investigators to be an unsuitable candidate for receipt of an
investigational drug.

8. The investigators may exclude participants who complete daily questionnaires on less
than half of the days between intake and treatment.