Rationale

Upregulation of α4β2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability.

Objective

We sought to determine if smokers with heavy caffeine or marijuana use have different levels of α4β2* nAChRs than smokers without these drug usages.

Methods

One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for β2*-containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability.

Results

A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use.

Conclusions

Smokers with heavy caffeine or marijuana use have higher α4β2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level.

Introduction

The majority of people with schizophrenia have a diagnosis of tobacco dependence during their lifetime. A major obstacle to reducing the burden of cigarette smoking in this population is that these smokers have lower quit rates when undergoing standard treatment compared to smokers with no mental illness. We sought to determine if combination extended treatment (COMB-EXT) and home visits (HV) would lead to improved outcomes in smokers with schizophrenia.

Methods

Thirty-four cigarette smokers with schizophrenia completed either COMB-EXT with HV, COMB-EXT without HV, or treatment as usual (TAU) (random assignment). COMB-EXT consisted of group cognitive-behavioral therapy (CBT), bupropion, nicotine patch, and nicotine lozenge, which were initiated within 2 weeks and continued for 26 weekly visits. HV consisted of biweekly visits to the home with assessment of secondhand smoke (SHS) exposure and brief behavioral therapy with participants and others in the home environment. TAU consisted of group CBT plus serial single or combination medication trials as per standard care.

Results

Smokers with schizophrenia who received COMB-EXT (with or without HV) had greater reductions in cigarettes per day than those treated with TAU (both ps < .01). In addition, 7-day point prevalence abstinence rates for the three groups were 45%, 20%, and 8%, respectively, which was significantly higher for COMB-EXT plus HV than TAU (χ²(1) = 4.8, p = .03). Groups did not differ significantly in the number of adverse events, and HV were easily scheduled.

Conclusion

COMB-EXT improves outcomes for smokers with schizophrenia. HV appeared to provide additional benefit for smoking cessation in this treatment-resistant population.

Implications

The clear benefit found here of rapidly initiated, combination, extended treatment over TAU suggests that aggressive and extended treatment should be considered in clinical practice for smokers with schizophrenia. Furthermore, HV to address SHS exposure showed initial promise for assisting smokers with schizophrenia in maintaining abstinence, indicating that this intervention may be worthy of future research.

In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [¹¹C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation. Forty-five participants (30 smokers and 15 non-smokers) completed the study and had usable data. Participants underwent a dynamic PET scanning session with bolus injection of [¹¹C]DAA1106 (with smokers in the satiated state) and blood draws during PET scanning to determine TSPO affinity genotype and plasma nicotine levels. Whole-brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (smoker vs non-smoker) and genotype as factors, thereby controlling for genotype. Smokers and non-smokers differed in whole-brain SUVs (P=0.006) owing to smokers having 16.8% lower values than non-smokers. The groups did not differ in injected radiotracer dose or body weight, which were used to calculate SUV. An inverse association was found between whole-brain SUV and reported cigarettes per day (P<0.05), but no significant relationship was found for plasma nicotine. Thus, smokers have less [¹¹C]DAA1106 binding globally than non-smokers, indicating less microglial activation. Study findings are consistent with much prior research demonstrating that smokers have impaired inflammatory functioning compared with non-smokers and that constituents of tobacco smoke other than nicotine affect inflammatory processes.

This corrects the article DOI: 10.1038/npp.2017.48.

Rationale

Microglia are the main immune cells in the central nervous system and participate in neuroinflammation. When activated, microglia express increased levels of the translocator protein 18 kDa (TSPO), thereby making TSPO availability a marker for neuroinflammation. Using positron emission tomography (PET) scanning, our group recently demonstrated that smokers in the satiated state had 16.8% less binding of the radiotracer [¹¹C]DAA1106 (a radioligand for TSPO) in the brain than nonsmokers.

Objectives

We sought to determine the effect of overnight smoking abstinence on [¹¹C]DAA1106 binding in the brain.

Methods

Forty participants (22 smokers and 18 nonsmokers) completed the study (at one of two sites) and had usable data, which included images from a dynamic [¹¹C]DAA1106 PET scanning session (with smokers having been abstinent for 17.9 ± 2.3 h) and a blood sample for TSPO genotyping. Whole brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (overnight abstinent smoker vs. nonsmoker), site, and TSPO genotype as factors, thereby controlling for site and genotype.

Results

Overnight abstinent smokers had lower whole brain SUVs (by 15.5 and 17.0% for the two study sites) than nonsmokers (ANCOVA, P = 0.004). The groups did not significantly differ in injected radiotracer dose or body weight, which were used to calculate SUV.

Conclusions

These results in overnight abstinent smokers are similar to those in satiated smokers, indicating that chronic cigarette smoking leads to global impairment of microglial activation which persists into early abstinence. Other explanations for study results, such as smoking leading to reduced numbers of microglia or smokers having more rapid metabolism of the radiotracer than nonsmokers, are also possible.