N-Acetyl Cysteine Plus Behavioral Therapy for Nicotine Dependent Pathological Gamblers

Among US adults, 12.8% report nicotine dependence, and nicotine dependence is highly
associated with a variety of DSM-IV Axis I and II disorders (Grant BF et al., 2004).
Pathological gambling (PG), a serious public health problem with detrimental effects on
individuals and families, and with an estimated yearly cost to society of 5 billion dollars
due to lost jobs, debt, bankruptcy, and incarcerations, is associated with elevated
proportions of nicotine dependence (41% - 55%), and tobacco smoking in clinical samples of
pathological gamblers has been associated with increased gambling severity and more frequent
psychiatric problems (Smart & Ferris, 1996; Crockfod & El-Guebaly, 1998; Shaffer et al.,
1999; Petry & Oncken, 2002; Potenza et al., 2004; Grant et al., 2005; Falk et al., 2006;
Fagan et al., 2007). In addition, research suggests that continued nicotine use is
associated with greater rates of relapse among pathological gamblers who received behavioral
therapy. Despite increased awareness of the relationship between nicotine dependence and PG,
and the possible effects of nicotine dependence on gambling severity, no previous research
has focused on how assessment and treatment of nicotine dependence may aid in the successful
treatment of PG or smoking cessation. Preliminary research suggests that behavioral therapy
using imaginal desensitization and motivational interviewing (IDMI) has shown promise in
reducing the symptoms of PG (Grant et al., in press). Despite the efficacy of treatments
for PG and nicotine dependence, relapse is common among individuals with nicotine dependence
and PG. Preclinical studies have suggested that levels of glutamate within the nucleus
accumbens mediate reward-seeking behavior and may underlie relapse seen in addictions.
N-acetyl cysteine, a dietary supplement, amino acid and cysteine pro-drug, appears to
modulate glutamate within the nucleus accumbens and has shown benefit in reducing the
reward-seeking behavior in individuals with cocaine dependence and in pathological gamblers
(Baker et al., 2003; LaRowe et al., 2006; Grant et al., 2006). If successful in treating
nicotine dependent pathological gamblers, N-acetyl cysteine may serve as a viable, low-cost,
and easily available treatment option for nicotine dependent pathological gamblers who
receive behavioral therapy.

We therefore propose to examine how a dietary supplement, N-acetyl cysteine, used in
combination with behavioral therapy, will affect both the urge to smoke and gamble in
nicotine dependent pathological gamblers and smoking and gambling behaviors. We therefore
propose a randomized placebo-controlled trial of N-acetyl cysteine or placebo with 80
nicotine dependent pathological gamblers who will all receive brief standardized smoking
cessation treatment (Ask, Advise, and Refer model) for nicotine cessation and 6 sessions of
IDMI for PG. We hypothesize that N-acetyl cysteine plus behavioral therapy will result in
greater reduction in both nicotine dependence and PG symptoms during the acute treatment
phase and will enhance greater long-term abstinence. Our research will contribute to an
improved understanding of the treatment of nicotine-dependent pathological gamblers as well
as a greater understanding of the treatment of co-occurring addictions. If our intervention
is successful, it will have the potential to set a new standard of care for a range of
psychiatric disorders that co-occur with nicotine dependence.