Sensitivity to Intravenous Nicotine: Genetic Moderators

Increasing evidence suggest that MOR contribute to nicotine's rewarding effect. Further, the
functional OPRM1 A118G variant has been linked to rewarding effects of alcohol in alcohol
users and to nicotine in female smokers. Since no previous studies examined the influence of
the A118G variation on pure nicotine responses, the next logical step is to evaluate how
this genetic polymorphism affects nicotine's rewarding, cognitive, and physiological effects
using IV nicotine administration in male and female smokers. In addition, the association of
the G398A polymorphism of the CHRNA5 gene (rs16969968) with maximal response to nicotinic
agonists justifies examination of this SNP as a moderator of IV nicotine sensitivity in
humans (Bierut et al. 2008). This SNP will be examined in an exploratory fashion since it is
not feasible to fully stratify the study sample for multiple SNPs. The frequency of
rs16969968 SNP ranges from 35%-42% among those of European ancestry, making it feasible to
examine this variation in our subject sample.

Currently this study is active and enrollment is continuing. Currently there are 205
completers and on going.(June 2014)

Inclusion Criteria:

- Female and male smokers, aged 18 to 50 years;

- History of smoking daily for the past 12 months, 10-25 cigarettes daily;

- Not seeking treatment at the time of the study for nicotine dependence;

- Have a FTND score of at least 5 and CO level > 10ppm;

- In good health as verified by medical history, screening examination, and screening
laboratory tests;

- For women, not pregnant as determined by pregnancy screening, nor breast feeding, and
using acceptable birth control methods.

Exclusion Criteria:

- History of major medical illnesses that the physician investigator deems as
contraindicated for the patient to be in the study;

- Regular use of psychotropic medication (antidepressants, antipsychotics, or
anxiolytics) and recent psychiatric diagnosis and treatment for Axis I disorders
including major depression, bipolar affective disorder, schizophrenia or panic
disorder;

- Abuse of alcohol or any other recreational or prescription drugs.