New neurobiological research suggests substantial contributions to the expression of opiate dependence from excitatory amino acid (EAA) pathways. New medications to attenuate opiate withdrawal might act directly at EAA receptors, or might pre-synaptically decrease EAA release. Agonists at kappa opioid and GABA-B receptors have been shown to inhibit EAA release. The specific medications to be tested, and the systems they act at, are the following: L-baclofen and gamma hydroxybutyric acid- GABA system; caramiphen- a non-opioid anti-tussive which is thought to decrease EAA release; and dynorphine - which is a kappa opioid agonist. New agents will be tested as suggested by basic science advances, and as new pharmaceuticals become available for human use. New medications will be tested using serial naloxone challenge tests (NCTs) in the same opioid-dependent subjects. The subjective, observable, physiological, and neuroendocrine responses to naloxone in subjects will be compared with active pre-treatment medication to identical challenges with placebo pre-treatment. These studies build upon extensive clinical experience, including that of the investigators, with the NCT. The studies will provide dose-response information by using three doses of the pre-treatment medication.
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