Recent federal estimates indicate there are at least 898,000 chronic users of heroin and 3,497,000 persons have had nonmedical use of a pain reliever in the past month. For persons entering treatment, the most common illicit drug used is heroin (243,523 persons) - surpassing both cocaine and marijuana (218,311 and 236,638, respectively). This suggests the need for continued development of new opioid dependence treatments. The Drug Addiction Treatment Act of 2000 allows physicians to prescribe schedule III-V medications that are FDA approved for the treatment of opioid dependence in office settings. However, the only medication currently approved is buprenorphine, and other pharmacotherapies, and especially those with low abuse potential, are needed for use in office-based settings. One candidate medication is tramadol, an atypical opioid. Tramadol is an effective analgesic that exerts agonist effects at the mu opioid receptor, but appears to have a low abuse potential. Tramadol has good oral bioavailability and is safe in the usual dose range used for analgesic purposes. There is anecdotal evidence that tramadol can be successfully used for non-complicated opioid withdrawal treatment, although there are no systematic studies testing tramadol when used for either opioid withdrawal or maintenance treatment. This grant proposes to conduct a series of human laboratory studies examining the pharmacological characteristics of tramadol. The overall goals of these studies are two-fold: to provide a careful characterization of tramadol's pharmacological profile of effects, and to determine this medication's potential value as a new agent for the treatment of opioid dependence in office-based settings. Specifically, the following questions will be addressed: 1) What is the relative efficacy of different doses of tramadol for suppressing symptoms of spontaneous opioid withdrawal, and how does this vary as a function of different levels of physical dependence? 2) What is the level of physical dependence produced by maintenance on daily doses of tramadol? 3) How effective are different maintenance doses of tramadol in blocking the effects of mu agonist opioids? 4) How do the pharmacological characteristics of tramadol compare to other drugs in a discrimination procedure? 5) What is the severity and time course of symptoms that occur when a person is tapered off opioids with tramadol, compared to a clonidine and buprenorphine? These studies of tramadol will provide an important pharmacological characterization of this medication's profile in humans, and also provide a foundation for its potential use as a pharmacotherapy that can be utilized in the office-based treatment of opioid dependence.