Evaluation to determine if auto-induction can be used as a surrogate measure of nicotine receptor up-regulation through an observational study using nicotine replacement therapy for two weeks and no intervention for two weeks.

Studies have shown that prolonged exposure to nicotine reinforces addiction. The act of smoking delivers nicotine through lungs into the blood stream. As a result, during smoking nicotine levels peak and then when smoking stops levels progressively diminish to a base (trough) level. At the peak level a smoker feels rewarded, but at the trough level a smoker starts to experience negative withdrawal affects and a desire to smoke. Nicotine Gum and Inhalers mimic this smoking behaviour maintaining a peak and trough regime, but nicotine patches do not. Instead, nicotine patches deliver a constant base dose considered to be either above that of the smokers trough level or at a level where negative withdrawal effects are reduced.

The question arises as to if nicotine levels delivered by a patch are constant and potentially above that of the baseline smokers level, does this reinforce the addiction and therefore contribute to the high long term relapse rate? To answer this question the investigators will be looking at metabolites which the body uses to breakdown nicotine and several other enzymes. These metabolites respond to the levels of nicotine in the blood stream by increasing or decreasing over time. By testing blood flow, blood and urine the investigators are able to gain an insight into how the body is dealing with a constant stable dose of nicotine rather than a peak and trough dose. In combination with the questionnaires the investigators will be able to determine the level of affect.

Inclusion Criteria:

• Smokers who currently smoke at least 10 cigarettes per day
• Aged between 18 and 75
• Informed consent
• Willingness to attempt to quit smoking for the period specified, initially with a transdermal patch for 14 days and then without any smoking cessation aids for a further 14 days.

Exclusion Criteria:

• Use of bupropion, champix or nicotine containing products other than cigarettes in the last 2 months
• previous reactions to NRT
• Pregnancy / Breast Feeding
• Uncontrolled hypertension
• Unstable angina
• Heart attack or stroke within the previous 6 months
• Severe Obesity as indicated by Body Mass Index (BMI) ≥35 (potential for slow release of nicotine from tissues)
• acute psychiatric illness, past history psychosis, suicidal ideation or current diminished capacity.
• Current treatment or recent diagnosis of cancer
• Current use of Phenobarbital or other anticonvulsant drugs (induction of metabolism of nicotine to cotinine)
• Renal failure (creatinine clearance<30ml/min - reduces metabolic clearance of cotinine and nicotine)

Available upon request