Enhancing Self Regulation Among Smokers

Inclusion Criteria: * Participants must smoke 10+ cigarettes/day for three or more years * Have a Fagerström Test for Nicotine Dependence score greater than or equal to 4 * Be willing to make a cessation attempt * Willing to comply with reinforced abstinence requirements for the three laboratory sessions * Willing to use appropriate birth control methods during study participation including oral contraceptives, barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse * Remain abstinent from alcohol and all non-prescription drugs prior to medication administration and testing sessions * Live with within a 50 mile radius of our research program and have reliable transportation * Consent to fast for a two-hour period prior to medication administration * Consent to random assignment to rapamycin (sirolimus) vs. placebo conditions Exclusion Criteria: * Dependence on other substances (may meet criteria for abuse) * Undergoing other smoking cessation treatment (e.g., nicotine replacement, Chantix) * Taking medications that may interact with the study medication or alter responding on any study measure * Are pregnant, nursing, or of childbearing potential and not using birth control * Present evidence of or a history of significant endocrine, cardiovascular, pulmonary, renal or neurological disease, as these conditions may affect heart rate or skin conductance measurement * Have significant liver impairment (as indicated by alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values that are three times the upper limit of normal) as rapamycin (sirolimus) is hepatically metabolized * Have an existing infection or immune system disorder as rapamycin (sirolimus) has known immunosuppressive properties * Have a history of or current psychotic disorder, severe major depression as evidenced by active and profound psychomotor retardation and/or persistent and intense suicidal ideation * Currently taking anti-arrhythmic agents, psychostimulants or any other agents known to interfere with heart rate and skin conductance monitoring * Have known or suspected hypersensitivity to macrolide compounds (such as rapamycin/sirolimus) * Taking medications that could adversely interact with study medication including but not limited to significant inhibitors of CYP2D6 or CYP3A4 (voriconazole, fluconazole, itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, etc.) or significant inducers of CYP3A4, such as anticonvulsants (carbamazepine, phenobarbital, phenytoin, etc.) and antibiotics (rifabutin, rifapentine, etc.) * Have a history of thrombocytopenia, idiopathic thrombocytopenia purpura (ITP), or with a current platelet count of less than 100,000 cells per mm3, * Have any unhealed wounds, including but not limited to oral ulcers, foot ulcers, or recent surgical or trauma wounds * Have any planned surgeries within the next month, including surgical dental procedures