A Double-Blind Comparison of Naltrexone and Placebo in Adults With Attention Deficit Hyperactivity Disorder

This will be a six-week, randomized, double-blind, placebo-controlled, parallel design study
of adult ADHD with naltrexone monotherapy. Eligible and consenting subjects will be
recruited into the study. The first visit will consist of a meeting with a study clinician
who obtains consent, assesses for eligibility, and completes study rating scales. After this
evaluation, subjects will complete a neuropsychological assessment and study rating scales
(two hours; this visit can take place over multiple days, if necessary). Subjects will then
be randomized to naltrexone (50 mg) once a day with breakfast or placebo at a ratio of 1:1
to be increased, if tolerated, to 100 mg by week 1.

Blood will be drawn for prolactin, basic metabolic panel, CBC, and LFT's at pre-baseline and
upon completion of the study. Ten cc's (approximately two teaspoons) of blood will be
required for the basic metabolic panel, CBC, and LFT's at each drawing. An additional five
cc's (approximately one teaspoon) of blood will be required for laboratory testing of
prolactin levels at each drawing. Dipstick urine drug testing will be done at pre-baseline.

Women of child bearing age will also have a urine pregnancy test at pre-baseline.

Although every effort will be made to encourage subjects to keep regularly scheduled
appointments, in the event that a subject is unable to come into the office within a
reasonable timeframe of a scheduled visit, and the treating research clinician feels that
subject safety will not be jeopardized by doing so, the clinician can conduct the visit with
the subject over the telephone. However, study evaluation visit (pre-baseline), baseline
visit, mid-point visit (week 3), or the final study visit may not be conducted over the
phone. Additionally, phone visits may not occur for two consecutive visits.

Inclusion Criteria

1. Male and female outpatients 18-55 years of age.

2. Diagnosis of ADHD, by Diagnostic and Statistical Manual-IV (DSM-IV) by clinical
evaluation by an expert clinician.

3. A CGI of 7 (among the most extremely ill patients) at the pre-baseline visit is
exclusionary, and any subject who presents a CGI-S of 7 at any point during the study
will be removed from participation.

4. Subjects presenting with a CGI-S score of 6 (severely ill) at two consecutive visits
after week 2 will be dropped from the study (i.e. A subject with a CGI of 6 at
his/her week 3 visit and at week 4 visit will be dropped from the study at the week 4
visit). Subjects who are dropped for severe or worsening symptoms after exposure to
the study medication will receive free follow up care as described in the detailed
protocol and protocol summary.

5. Subjects treated for anxiety disorders and depression who are on a stable medication
regimen for at least one month, and who have a disorder-specific CGI-Severity score ≤
3 (mildly ill) and who have a score on the Hamilton-Depression and Hamilton-Anxiety
rating scales below 15 (mild range).

Exclusion Criteria

1. Any clinically unstable psychiatric conditions including any history of psychosis or
mania, suicidality, sociopathy, criminality, or delinquency.

2. Current (last 3 months) substance use disorders (alcohol or drugs),

3. Medical condition or treatment that will either jeopardize subject safety or affect
the scientific merit of the study including cardiovascular disease, current untreated
hypertension, or history of renal or hepatic impairment.

4. A condition that will or may require treatment with opioid analgesics.

5. Clinically significant abnormal baseline laboratory LFT's, which is defined as LFT's
greater than the ULN.

6. Mental retardation (IQ < 80).

7. Organic brain disorders including delirium, dementia, seizures, stroke, neurosurgery,
and head trauma with loss of consciousness.

8. Pregnant or nursing females.

9. Subjects with current adequate treatment for ADHD.

10. Any other concomitant medication with primarily central nervous system activity other
than specified in Concomitant Medication portion of the protocol (a stable and
effective treatment regimen of an SSRI or benzodiazepine is permitted per clinical
review).

11. Non-English speaking subjects will not be allowed into the study for the following
reasons:

1. The assessment instruments are unavailable and have not been adequately
standardized in other languages;

2. Even if such translation services were available, the assessments in the English
language conducted by English-speaking clinicians and raters with
English-speaking subjects are already extremely time-consuming, lasting many
hours, making it unfeasible, unrealistic, and of dubious clinical validity to
conduct them with a translator with non-English-speaking subjects;

3. Psychiatric questionnaires and evaluations are taxing, and adding the complexity
of a translator has the potential to make the patient experience even more
exhausting.