Methadone is commonly used in the treatment of opiate dependence. Methadone maintenance patients may also take a variety of drugs, notably benzodiazepines, before or after taking their daily dose of methadone. Oral doses of methadone are commonly administered in clinics at the same time each day and typically consumed by patients in a single swallow. Patients are instructed to ingest take home doses at 24 hour intervals. However, little is known of the actual administration pattern or consequences of patient determined variations in dosing over successive take home doses. Behavioral effects of the combined drug intake are also not well understood except at a gross observational level. The characteristics of this therapeutic drug ingestion provide a unique opportunity to elucidate these issues through systematic examination of oral drug taking in a controlled laboratory setting. The proposed studies (I-IV) will examine the effects of work requirements, time since last dosing session, and """"""""pretreatment"""""""" dosing with methadone or diazepam on methadone self-administration. Subjects will be patients (males, females, including minorities) stabilized on methadone. They will be asked to attend regular daily sessions. These will take place in a controlled, automated, human laboratory environment. Meeting response, or """"""""work"""""""" requirements will result in delivery of a small fraction of the individuals daily methadone dose. Successive completions of work requirements will produce successive drug deliveries. We will examine the effect of increasing the work requirement on drug deliveries obtained and investigate these requirements in relation to drug concentration delivered. We will also examine the time between sessions on the work output; thus in some experiments, sessions will be scheduled at 12, 36, or 48 hours following the previous session while the standard baseline intersession interval will be 24 hours. This will parallel patient determined variations in interdose interval when take home doses are provided. In the converse case, a portion of the total daily dose will be delivered before the self-administration session and the effects of these pretreatment doses will be examined. Finally, the effects on methadone self-administration of administering doses of diazepam prior to the sessions will be examined. These studies, in combination, will provide a better understanding of (i) the behavior of human methadone self-administration, (ii) reinforcing properties of methadone under a wide variety of conditions, (iii) effects of methadone administered across a range of conditions, and (iv) the relationship between methadone self-administration and use of other abused drugs. The research will provide a unique and important link between traditional clinical findings and other laboratory work. It will also clarify longstanding assumptions about therapeutic and illicit drug taking in this patient population.
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