Cognitive Enhancement as a Target for Cocaine Pharmacotherapy

This will be a double-blind, placebo-controlled, randomized clinical trial. One hundred and
twenty cocaine-dependent men and women will be randomized to one of three treatment groups:
placebo (n=40), 8 mg/day (n=40), and 16 mg/day (n=40) of extended release (ER) galantamine.
An urn randomization will be used to balance the groups for gender, severity of cocaine use
(measured by days of cocaine use), baseline cognitive functioning [determined via the Shipley
Institute of Living Scale (SILS)], and smoking status. Gender and severity of cocaine use
have been shown to predict treatment responses in cocaine users (76). Similarly, balancing
the treatment groups for baseline cognitive functioning, assessed with the SILS scores, will
minimize the influence of baseline differences on cognitive outcomes (77, 78). Smoking status
is also an important baseline variable, given galantamine's actions on nicotinic receptors
and its potential efficacy for smoking cessation (65). The initial dose of galantamine will
be 8 mg/day as a single dose, as recommended for clinical use. For those assigned to 16
mg/day, the dose of galantamine will be increased to 16 mg at the end of week 4. Treatment
groups will remain on their full dosage through week 13. All participants will receive
contingency management (CM) targeting treatment compliance. In three previous cocaine
pharmacotherapy trials using bupropion, desipramine or levodopa, medication efficacy on
cocaine use was evident only when medications were combined with CM, but not with standard
care (79-81). These findings provide a strong rationale for using CM in our clinical trial.

Recruitment is continuing. This protocol was amended as of May 2014 to come to one dispensing
visit and up too, two clinic visits. The payment has changed from gift cards to cash. This
change should help increase the number of completers.

Currently there are 40 completers with 9 active and 6 in follow up phase. The follow up phase
ended June 2016. Currently in analysis.

Inclusion Criteria:

1. Male and females, between the ages of 18 and 60

2. Are using cocaine more than once per week in the previous 30 days, provide a
cocaine-positive urine specimen at screening, and fulfill criteria for current cocaine
dependence according to DSM-IV

3. For women of child-bearing age, have a negative pregnancy test at screening, agree to
adequate contraception to prevent pregnancy, and agree to have monthly pregnancy tests

4. Are fluent in English and have a 6th grade or higher reading level; AND

5. Can commit to at least 13 weeks of treatment and are willing to be randomized to
treatment

Exclusion Criteria:

1. Meet DSM-IV psychiatric classifications for lifetime schizophrenia or bipolar
disorder, or have a depressive or anxiety disorder with current use of a prescribed
psychotropic medication that cannot be discontinued

2. Current DSM-IV diagnosis of drug or alcohol dependence (other than cocaine, or
tobacco)

3. Demonstrate significant medical conditions, including asthma or chronic obstructive
lung disease, history or current gastrointestinal ulcer, hepatic or renal deficit and
cardiac rhythm disturbances or any other medical conditions that the study physician
deems contraindicated for galantamine treatment

4. Use of other medications including:

- drugs that slow heart rate (e.g., beta-blockers), which may increase the risk of
bradycardia and atrioventricular (AV) block and

- non-steroidal anti-inflammatory drugs (NSAIDs); increased potential for
developing ulcers/active or occult gastrointestinal bleeding

5. Have a screening liver function test (AST or ALT) greater than 3 times normal; OR

6. Known allergy or adverse reaction to galantamine