The objective of this study is to determine whether aprepitant blocks the opiate reward system in non-dependent opiate abusers, indicating its potential as a safe, non-addictive first line therapy for early heroin abuse.

This initial proof-of-concept study focuses on evaluating whether an NK1 antagonist, aprepitant, can block opiate reward in non-dependent opiate experienced volunteers in response to a standard opiate challenge. Sixty subjects will be included in a randomized controlled study. Following a training challenge session, they will receive 1 week treatment with aprepitant or matching placebo, followed by a challenge session during which subjective and physiological responses to the opiate partial agonist buprenorphine will be assessed.

Inclusion Criteria:

• Age 18 - 50
• Current opiate use, without dependence

Exclusion Criteria:

• Clinical diagnosis of opiate dependence
• Positive urine screen for opiates on day of challenge sessions
• Meet diagnostic criteria for any other substance abuse disorder except nicotine within the last 12 months.
• Any ongoing prescription medication other than oral contraceptives or hormone replacement
• Any serious medical condition which in the judgment of the investigators makes administration of opiates medically inappropriate.