Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal

Inclusion Criteria: * Adults between the ages of 21 and 45 * Current dependence on heroin according to (Diagnostic and Statistical Manual) DSM-IV criteria * Non-treatment seeking Exclusion Criteria: * Female participants who are currently pregnant or breastfeeding. Lack of effective birth control 10 days before Study Day 1 (15 days prior to the first PET scan) * Self-reported use of methadone, buprenorphine, or levo-alpha-acetylmethadol (LAAM) in the past 14 days * Participants who have a positive history of neurological illness (including epilepsy) or those who have received anti-convulsant therapy during the past 5 years * Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit of normal * Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment * Neurological or psychiatric disorders including psychosis, bipolar disorder, organic brain disease, any seizure history or other disorders that require treatment or that could make study compliance difficult * Positive tuberculosis (PPD) TB skin test along with a clinical history and chest X-ray indicative of active tuberculosis. (Individuals who have a positive PPD test and have a negative chest X-ray, are not symptomatic for tuberculosis, and do not require anti-tuberculosis therapy will be eligible to participate. Participants will be asked if they ever tested positive for tuberculosis. If so, they will not be given a PPD and a chest X-ray and clinical history will be used for evaluation purposes). * Presence or positive history of severe medical illness or any cardiovascular disease or heart abnormality, such as low hemoglobin (Hb \< 13 g/dL in males, Hb \< 11 g/dL in females), or BP \> 150/90. * Requirement for any of the following medications (current or within the past 4 weeks): psychotropics (including sedative/hypnotics, antidepressants, neuroleptics), anticonvulsants, antihypertensives, antiarrhythmics, or antiretroviral medications,. Participants on any current psychoactive prescription medications will be excluded. * Current dependence (by DSM-IV criteria) on methadone, LAAM, or buprenorphine * Participants for whom detoxification is not "clinically recommended" such as those with a significant history of overdose following detoxification * Participation in an investigational drug study within the past 3 months * Hypersensitivity to any of the medications used in this study * Participants who are positive for HIV or chronic active hepatitis * Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock Frank G., Lippincott Williams \& Wilkins Healthcare, Philadelphia, 2001. * Lifetime exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols, in the past year * Positive Allen Test indicating lack of collateral blood flow to hand * History of Reynaud's syndrome