Nicotine Vaccination and Nicotinic Receptor Occupancy

The purpose of the present study is to examine the occupancy of brain β2-containing nicotinic acetylcholine receptors (β2-nAChR) by nicotine both at baseline and following administration of a nicotine vaccine. The number of brain β2-nAChR and the amount of nicotine occupancy both before and after vaccination will be measured using the nicotinic agonist [123I]5-IA-85380 ([123I]5-IA) and single photon emission computed tomography (SPECT). [123I]5-IA will be administered using the bolus plus constant infusion paradigm to smokers abstinent for 4-9 days (time period necessary for nicotine and pharmacological active metabolites to clear from brain). Three baseline SPECT images will be obtained after equilibrium has been reached (~6 hours into the [123I]5-IA infusion). Then, IV nicotine will be administered (0.5-1.5 mg/70 kg will be infused over 10 minutes). Following a series of 4 nicotine vaccine shots, the same procedure will be repeated for a second [123I]5-IA scan day. We hypothesize that occupancy of β2-nAChR will be significantly lower, and take longer to plateau, following nicotine vaccine administration.

Inclusion criteria

• Current smoker who smokes at least 10-25 cigarettes a day
• Good general health

Exclusion criteria

• Subjects with a pacemaker or other ferromagnetic material in body.
• Prior exposure to NicVAX or any other nicotine vaccine.
• Use of systemic steroids or other immunosuppressive agent
• History of significant neurological, cardiovascular, hepatic, endocrine, renal, liver, psychiatric or thyroid illness
• Cancer or cancer treatment in last 5 years
• HIV infection
• Use of varenicline (Chantix), bupropion (Wellbutrin, Zyban), mecamylamine (Inversin), within 30 days prior to administration of NicVAX and for the duration of the study.
• Inability to fulfill all visits and examination procedures for approximately 20 weeks.