The goal of this clinical trial is to target one of the major complaints from Veterans with Gulf War Illness (GWI) -- namely chronic pain and inflammation -- with a compound that has a history of safe use in humans and has been shown to be effective in animal models of exposure to agents known to have caused GWI. Chronic musculoskeletal pain and associated inflammation are some of the most debilitating symptoms of GWI. Identifying effective, safe, and tolerable treatments will alleviate major aspects of the multisymptom condition that as yet has no effective treatment. In a recent presentation of data from the national War Related Illness and Injury Study Centers (WRIISC) in California, New Jersey, and Washington, DC, the reported major complaints of Veterans, and specifically of GW Veterans, was pain (90%), exceeding the next most prevalent symptom, fatigue, by threefold. For many years now, our GWI research program has been developing and characterizing mouse models of exposure to agents known to have been involved in causing GWI, such as the nerve gas prophylactic Pyridostigmine Bromide and pesticides such as Permethrin. In order to best model the human condition, now presenting more than 23 years after the war, we give exposures for 10 days, and then evaluate changes occurring over months and years. We investigate changes in behavior, in the brain and the blood, to identify cellular mechanisms and functions that have been disrupted as a consequence of the exposures, and that we may target with therapeutic approaches. Our work has demonstrated an evolving and persistent inflammation in these animals, consistent with the reports and complaints from GWI patients. Chronic pain is not easily evaluated in mouse models, but we have noted behavioral and cognitive changes in mice following these exposures. Our scientific team has a lot of experience with animal models of conditions where inflammation plays an important role, and with treatments that target inflammation. Over the last few years, we have carried out extensive work on the dietary supplement anatabine (Rock Creek Pharmaceuticals, Inc.), which is a naturally occurring compound found in tobacco, tomatoes, eggplant, and peppers. Our work has shown that it has strong anti-inflammatory properties. Based on sales, an estimated 300,000-500,000 individuals used these products with positive effects demonstrated, including pain alleviation and only minor adverse effects reported. Anatabine products are no longer available as dietary supplements as the company is pursuing pharmaceutical use for these products. Furthermore, we have conducted clinical studies of anatabine in healthy human subjects, which demonstrated its safety and tolerability. We then investigated the effects of anatabine in our mouse model of GWI and found improvement of behavioral symptoms and reduced inflammation in the exposed animals. Therefore, we now propose a clinical evaluation of anatabine in a small population of GWI patients, comprising 11 weeks of treatment and 11 weeks of placebo (or vice versa) and an evaluation of the effects on pain and other related conditions. To the best of our knowledge, this is the first time that data from a laboratory model of GWI has been partnered with data from human clinical exposure to support a potential GWI treatment. If successful, then this trial will lead to a larger scale trial of several hundred GWI patients across multiple sites, which in turn would support an application to the Food and Drug Administration (FDA) for anatabine as a treatment for GWI. Given the extreme prevalence of chronic pain in the GWI patient population, we believe that this may potentially benefit most GWI patients. Treatment with anatabine provides a major advantage for the ill GW Veteran population currently using opioids or other potentially addictive pain relievers. The trial proposed will be completed in 2018, and the infrastructure to support a larger follow-up study already exists through extensive collaborations and consortia that have been established in the GWI research community. This will allow for a larger validation study that could potentially be underway by 2019. Targeting inflammation may have beneficial effects on many aspects of GWI, including gastrointestinal symptoms and cognitive function, and this work may lead to investigation of other anti-inflammatory compounds acting through the same cellular mechanisms, as there are likely to be additional factors including genetic predispositions that may differentially influence an individual's response to treatment.