# Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

## TL;DR

Smoking lowers brain levels of a marker linked to brain cell stress, but this effect reverses after just three days of not smoking.

## Contribution

This study shows that short-term smoking abstinence normalizes a brain marker of gliosis previously suppressed by smoking.

## Key findings

- Smokers who smoked before scanning had 15.3% lower brain marker levels than nonsmokers.
- Three-day abstinence normalized the brain marker to nonsmoker levels.
- Higher marker levels in abstinent smokers correlated with worse mood ratings.

## Abstract

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking‐related symptoms. This observational study was performed in an academic VA medical centre. Fifty‐nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [18F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [18F]FEPPA binding than both the nonsmoking (−15.3%) and abstinent smoker (−12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

Cigarette smoking is associated with low levels of whole brain (WB) binding of a PET radioligand for the translocator protein, a marker for gliosis. Here, we demonstrate that, compared to non‐smoking controls (group 0), this PET marker is lower in smokers who smoke to satiety prior to scanning (group 1), but is comparable between non‐smokers and smokers who maintain abstinence for 3 days (group 2). Study findings indicate that a potentially detrimental health effect of smoking resolves with short‐term abstinence.