Inclusion Criteria:

• Age Aged between 18 and 55 years inclusive.

• Weight and size

  1. Body mass index (BMI) within the range 19.0-32.0 kg/m.
  2. Able to fit comfortably within the MR scanner.

• Smoking Status

  1. Cigarette smokers that consume their first manufactured cigarette (i.e., not self rolled cigarettes) within 30 min of waking.
  2. Individuals who have smoked regularly for at least a year.

• General Status

  1. Right handed subjects.
  2. Able to read and write (in English) at a level sufficient to complete study related assessments.
• Contraception Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.
• Compliance Understands and is willing, able and likely to comply with all study procedures and restrictions.
• General Health Good general health with (in the opinion of the examining study doctor) no clinically significant and relevant abnormalities of medical history, physical examination or clinical laboratory test.
• Consent Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.

Exclusion Criteria:

• Pregnancy Women who are pregnant or who have a positive urine pregnancy test.
• Breast-feeding Women who are breast-feeding.

• Disease/Illness

  1. Any clinically significant medical history or abnormality found on physical examination, laboratory assessment or electrocardiogram (ECG) at screening which, in the opinion of the investigator, could interfere with the interpretation of efficacy or safety data or which otherwise would contraindicate participation in a clinical trial.
  2. Current or recent history or presence of a neurological diagnosis (not limited to but including for example, stroke, traumatic brain injury, carotid arterial sclerotic disease, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, major depression etc.) that may influence the outcome or analysis of the scan results.

• Contraindications to MR scanning

  1. Intracranial aneurysm clips (except Sugita).
  2. History of intra-orbital metal fragments that have not been removed by a doctor (as confirmed by orbital X-Ray).
  3. Inner ear implants.
  4. Tattoos with metal containing inks or piercings that can not be removed except those, which, in the opinion of the Investigator, will not interfere with the study procedures or compromise safety.
  5. History of claustrophobia or subject feels unable to lie still on their back for a period of 90 min in the MR scanner.
  6. Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI questionnaire supported by plain X-Rays where appropriate.

• Prior/Concomitant Medication

  1. Use of any central nervous system (CNS) active, prescription medication within 14 days of first treatment visit.
  2. Use of any over the counter (OTC) medication within 14 days of each treatment visit except those, which, in the opinion of the Investigator, will not interfere with the study procedures or compromise safety. Paracetamol (up to 2 g) may be taken up to 24 hrs prior to each treatment visit.
  3. Current use of any nicotine replacement therapy.

• Clinical Study/Experimental Medication

  1. Participation in another clinical study or receipt of an investigational drug within 3 months of the first treatment visit.
  2. Previous participation in this study.
• Allergy/Intolerance Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.

• Substance abuse

  1. History of regular alcohol consumption exceeding an average weekly intake of more than 14 units per week for females, 21 units per week for males, or an average daily intake greater than 2 units for females and 3 units for males.
  2. Past history of drug abuse (i.e. meeting DSM IV [American Psychiatric Association, 1994] or ICD 10 [World Health Organization, 1990] criteria for substance dependence), excluding nicotine, or has tested positive for urine drugs of abuse at the screening or either treatment visit.
• Alcohol Consumption of any alcoholic beverages within 24 hours of the treatment visits (as indicated by either a positive breath alcohol test or in the opinion of the Investigator).
• Caffeine Consumption of large quantities of xanthine containing beverages (e.g., coffee, tea, cola, chocolate etc, more than an average of five cups or glasses per day).
• Personnel An employee of the sponsor or the study site or members of their immediate family.