The overall objectives of this clinical study are to determine in smokers the short term effects of switching to tobacco products that deliver low levels of nicotine or reactive oxygen/nitrogen species (ROS/RNS) on smoking behavior and biomarkers of tobacco smoke exposure and oxidative stress.

Researchers at Penn State Hershey are seeking healthy adult cigarette smokers between 21-65 who smoke any of the following brands on a regular basis: Marlboro Red, Marlboro Menthol, Pall Mall Red, Pall Mall Menthol, Kool Menthol, Salem Menthol, L&M Menthol, Pyramid Red, Newport Red, Newport Menthol.

If you smoke one of these brand styles on a regular basis you may be eligible to participate in a compensated short term study on health and smoking behavior at Penn State Hershey Medical Center.

Study participation lasts 22 days, with 4 study visits at the Medical Center. Smokers are asked to use their usual brand for one week and then switch to 1 of 3 brands for the remaining two weeks. The three brands participants are randomly assigned to after the first week of participation are either Group 1. reduced nicotine content cigarette (Spectrum Research Cigarettes) or Group 2. reduced oxidant cigarette (American Spirit) or assigned to Group 3. usual brand. Whichever group you are assigned to, you will be asked to smoke only these until the end of the study. All cigarettes following visit 1 will be provided free of charge.

Study overview:

Visit 1/ Duration: 60 minutes Provide a blood and urine sample Complete a 20 minute interview Use a simple, hand held smoking device to smoke all cigarettes for 2 days Collect cigarette butts on 1 day

Visit 2: Randomized Phase /Duration: 20-30 minutes Provide a blood and urine sample Complete a 10 minute interview Use a simple, hand held smoking device to smoke all cigarettes for 2 days Collect cigarette butts on 1 day

Visit 3/ Duration: 20-30 minutes Provide a blood and urine sample Complete a 10 minute interview Use a simple, hand held smoking device to smoke all cigarettes for 2 days Collect cigarette butts on 1 day

Visit 4/ Duration: 20-30 minutes Provide a blood and urine sample Complete a 10 minute interview Sign compensation form

For information on additional tobacco studies being conducted at Penn State Hershey, please call 1-844-207-6392

*This research is being conducted under the investigator John Richie at Penn State Hershey; 500 University Drive Hershey, PA

Inclusion Criteria:

• Age 21-65
• Smoke 10 cigarettes/day or more for at least one year
• Read and write in English
• Menthol and nonmenthol smokers who use relatively high nicotine and ROS/RNS cigarettes
• Able to understand and provide consent to study procedures
• Plan to live in the local area for the next month
• Women not pregnant or nursing and taking steps to avoid pregnancy
• No quit attempt in the last one months and not planning to quit in the next month

Exclusion Criteria:

• Currently pregnant or nursing
• Unstable or significant medical condition, such as COPD or kidney failure, that is likely to affect biomarker data
• Use of non-cigarette nicotine delivery product in the past week (included cigars, pipes, chew, snus, hookah, e-cig, and marijuana)
• Currently reducing or planning to reduce cigarette consumption in the next month
• Use of smoking cessation medicine in the past 3 months
• History of difficulties providing blood samples: fainting, poor veins, anxiety, etc.
• Uncontrolled serious psychotic illness or substance abuse or inpatient treatment for these in the last 6 months (substance abuse includes weekly, almost daily or daily use of other illegal drugs and prescription drugs that are not being used for medically prescribed purposes or alcohol abuse that would hinder the participant's ability to participate)
• Significant medical condition, i.e. stroke, MI, cancer, in the last month
• Currently using illegal drugs

At this time we have no plan for sharing, however if need should arise, then sharing may be a possibility.