Proof-Of-Concept Investigation With a Neurosteroid Analog (Ganaxolone) as a Smoking Cessation Candidate

Inclusion Criteria: * Have no known serious medical conditions; * Are 18-65 years old; * Smoke an average of at least 10 cigarettes per day; * Have smoked at least one cumulative year; * Have an expired air CO reading of at least 10ppm; * Able to read and understand English; * Express a desire to quit smoking in the next thirty days. Potential subjects must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study: * participation in any other nicotine-related modification strategy outside of this protocol; * use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco; * use of experimental (investigational) drugs or devices; * use of illegal drugs; * use of opiate medications; * consumption of grapefruit or grapefruit juice for the first six weeks of study participation; * use of melatonin; * use of sedating antihistamines for the first six weeks of study participation; * use of alcohol during the first six weeks of study participation. * use of benzodiazepines Exclusion Criteria: * Inability to attend all required experimental sessions; * Inability to take oral drugs or adhere to medication regimens; * Hypertension (systolic \>140 mm Hg, diastolic \>90 mm Hg); * Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). * Coronary heart disease; * Lifetime history of heart attack; * Clinically significant cardiac rhythm disorder (irregular heart rhythm); * Chest pains; * Cardiac (heart) disorder; * Extensive active skin disorder; * Liver or kidney disorder; * Gastrointestinal disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Currently symptomatic lung disorder/disease; * Brain abnormality; * Migraine headaches that occur more frequently than once per week; * History of seizures; * Recent, unexplained fainting spells; * Problems giving blood samples; * Diabetes (unless treated with diet and exercise alone); * Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); * Other major medical condition; * Current symptomatic psychiatric disease; * Current depression; * Current suicidal ideation or history of suicide attempt (in the past 5 years); * Pregnant or nursing mothers; * Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive), * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, antipsychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Corticosteroids; * Cytochrome P450 341 (CYP3A4) inhibitors and inducers; * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine replacement therapy or any other smoking cessation aid. * Use (within the past 14 days) of: * dehydroepiandrosterone (DHEA), Pregnenolone or ganaxolone; * Opiate medications for pain or sleep; * Benzodiazepines or other drugs with significant sedating or anticholinergic activity; * Use of more than one cigar a month; * Regular alcohol use; * Significant adverse reaction to nicotine patches in the past. * Significant past adverse reaction to ganaxolone in the past. * Current participation or recent participation (in the past 30 days) in another smoking study at our center or another research facility. * Current participation in another research study.