Prediction of brain nicotine accumulation during cigarette smoking using data obtained after a single puff of 11C-nicotine containing cigarettes

Objectives The results from tobacco smoking studies highlight the importance of brain nicotine dynamics in the manifestation of its pharmacological effects. Previously (Rose et al., PNAS 2010) we investigated the brain nicotine accumulation after a single puff of a cigarette and predicted that: 1) brain nicotine concentration gradually increases over the course of smoking a cigarette and 2) brain nicotine accumulation during cigarette smoking can be calculated based on the assessment of brain nicotine kinetics after a single puff. To confirm these predictions, here we assessed the brain nicotine accumulation after a single puff and during the smoking of a whole cigarette containing 11C-nicotine evenly distributed along the tobacco rod.

Methods Sixteen regular smokers (10+ cigarettes/day) participated in two separate PET sessions. Each subject’s head was scanned over 720 sec (245 frames) after inhalation of a single puff or 7 puffs (45 sec inter-puff interval) of smoke from a cigarette containing 11C-(S)-nicotine.

Results Brain nicotine concentration increased in a nearly linear fashion during the 6 min of cigarette smoking (average R2 = 0.99) and reached the max value of 4.6 ± 0.2 %ID/kg tissue at 6-7 min after the first puff. The predicted brain nicotine concentration curves for smoking a full cigarette, calculated by convolution of single puff curves, were practically superimposable on those assessed directly (respective average slopes were 0.87 ± 0.05 and 0.82 ± 0.05 %ID/kg tissue/min; correlation between slopes r = 0.95).

Conclusions These results confirm that the kinetics of brain nicotine concentration during the smoking of a full cigarette can be accurately calculated using data on nicotine kinetics after a single puff of a cigarette. This opens a new perspective to study the role of brain nicotine kinetics in smoking dependency.

Research Support NIH grant RC2DA028948