This will be an open label clinical trial with all subjects receiving both lorcaserin and varenicline with a primary aim of reducing post cessation weight gain.

This will be an open label clinical trial with all subjects receiving both lorcaserin and varenicline. The investigators will obtain preliminary data on the efficacy of lorcaserin (10 mg twice daily) for 12 weeks in 20 adult weight-concerned cigarette smokers with a BMI of 27 to 40 simultaneously receiving 12 weeks of open-label varenicline and a behavioral intervention to assist with stopping smoking. Secondary aims will be weight, waist circumference, and smoking cessation.

Inclusion Criteria:

1. ≥18 years and ≤65 years of age;
2. smoked ≥10 cigarettes/day for the past 6 months;
3. BMI of 27-40 kg/m2;
4. resides within the Olmsted County area;
5. motivated to stop smoking;
6. weight concerned as shown with the Weight Concern Scale;
7. able to participate fully in all aspects of the study;
8. understood and signed the study informed consent.

Exclusion Criteria:

1. current nonspecific suicidal thoughts or a lifetime history of a suicidal attempt (defined by the Columbia-Suicide Severity Rating Scale [C-SSRS] as a "potentially self-injurious act committed with at least some wish to die, as a result of act.");
2. current moderate or severe depression as assessed by a score of ≥16 on the Center for Epidemiologic Studies-Depression (CES-D);
3. a lifetime history of bipolar disorder or schizophrenia;
4. use of anti-psychotic medication within the past 30 days;
5. use of weight-loss medications within the past 30 days or current participation in a program specifically designed to help with weight loss;
6. weight fluctuations of 20 pounds or more in the past 6 months (self-report);
7. use of any treatments for tobacco dependence within the past 30 days;
8. use of an investigational drug within the past 30 days;
9. recent history (past 3 months) of abuse of or dependence on a substance other than tobacco;
10. current use of benzodiazepines, narcotics, anti-epileptics, or other medications known to interact with lorcaserin (see human subjects section);
11. current use of triptans, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), dextromethorphan, tricyclic antidepressants (TCAs), bupropion, lithium, tramadol, tryptophan, and St. John's Wort, or any other medication known to involve the serotonergic neurotransmitter system (see human subjects section);
12. uncontrolled hypertension (systolic >160 mm Hg and/or diastolic >100 mm Hg) documented on 2 separate occasions;
13. clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, respiratory, or metabolic disease;
14. current use of medications known to interact with varenicline or lorcaserin;
15. another household member or relative participating in the study;
16. Known Diabetes;
17. a known allergy to varenicline or lorcaserin;
18. have taken antibiotics within the past 3 months.
19. Women who are pregnant or lactating, or who are of childbearing potential and are likely to become pregnant during the medication phase but are not willing to use a reliable form of contraception, will also be excluded. Reliable forms of contraception include oral contraception, diaphragm or condom (with spermicide), injections, intrauterine device, surgical sterilization, and abstinence.

12 weeks