A Placebo-Controlled Double-Blind Combined Treatment of Modafinil and CBT for Cocaine Dependence

Chronic cocaine abuse has been documented to produce cognitive impairments in various
domains. The observed cognitive deficits in the substance abuse population include, but are
not restricted to, attention, concentration, verbal and nonverbal memory, problem solving
and abstract reasoning. Our recent studies (IRB Protocol # 3998) demonstrated that in
cocaine dependent participants such cognitive deficits have been shown to: 1) negatively
effect retention and 2) impede the ability of the drug abuser to benefit from cognitive
behavioral therapy- relapse prevention (CBT-RP) that requires participant to attend to novel
stimuli, integrate new information with existing stores, and translate information into
behavior change (Aharonovich, Hasin & Nunes, 2003; Aharonovich et al, in press).
Furthermore, the toxic effects of cocaine together with withdrawal symptoms, such as fatigue
and hypersomnia make it difficult to fully engage in any psychosocial intervention including
CBT-RP.

Recent findings indicate that cocaine dysregulates reward-related glutamate pathways (Dackis
& O’Brien, 2003; Kalivas et al, 2003). Modafinil is a medication known to improve
attention, increase wakefulness, energy, and alertness in part by increasing glutamate
levels. In light of this work and the negative affect of cognitive impairments on treatment
outcomes, testing cognitive enhancing medications that act on glutamate pathways is a novel
promising strategy for improving treatment for cocaine dependence. Modafinil is approved
for sleep disorders and is a relatively safe medication for cocaine-dependent participants
as it has a low abuse potential and has shown promise in a double blind placebo controlled
trial for cocaine dependence (Rush et al, 2002; Jasinski, 2000, Dackis et al, 2005). We
therefore propose a double blind placebo controlled 12-week exploratory pilot study of
modafinil, a “wakefulness agent,” in conjunction with sessions of CBT-RP enhanced with
motivational interviewing components.

Inclusion Criteria:

- Meets DSM﷓IV criteria for current cocaine dependence and is seeking treatment.

- Used cocaine at least eight days in the past month or reports episodic binges of
large amounts of cocaine (at least $150 worth) at least twice per month

- Able to give informed consent and comply with study procedures.

Exclusion Criteria:

- Meets DSM﷓IV criteria for current mood disorder or past or current mania (i.e.
bipolar disorder), schizophrenia or any psychotic disorder other than transient
psychosis due to drug abuse.

- Baseline 21 item Hamilton Depression Scale scores ≥ 15

- History of seizures

- Chronic organic mental disorder.

- Significant current suicidal risk.

- Pregnancy, lactation, or failure in sexually active female participants to use
adequate contraceptive methods.

- Unstable physical disorders, which might make participation hazardous such as
hypertension, hepatitis, participants with mildly elevated AST and ALT levels (< 3 X
upper limit or normal are acceptable), or diabetes.

- Coronary vascular disease as indicated by history, or suspected by abnormal EKG or
history of cardiac symptoms.

- Current use of prescribed psychotropic medications.

- Current use of medications that interact with modafinil: Tricyclic anti-depressants;
MOA Inhibitors; diazepam; phenytoin and medications containing Ethinyl Estradiol

- Known hypersensitivity to modafinil

- Currently meets DSM-IV criteria for narcolepsy

- Currently meets DSM-IV criteria for ADHD

- Currently meets DSM-IV criteria for opioid or sedative-hypnotic dependence.

- Currently meets criteria for DSM-IV alcohol dependence with evidence of clinically
significant physiological dependence in need of medically supervised detoxification.

- Current cannabis dependence is identified as the main problem—i.e. participants with
current DSM-IV cannabis dependence are eligible, as long as cocaine is identified by
the participant as the primary substance problem for which they are seeking
treatment.

- Gross visual or auditory impairments

- First language is not English and received NO formal education in English-speaking
school