Relationship between rate of infusion and reinforcing strength of oxycodone in humans

Abstract

The rate of drug delivery to the central nervous system is believed to be an important predictor of the reinforcing strength of a drug. However, only a few studies have directly examined the relationship between drug-taking behavior and rate of drug administration. The purpose of the present experiment was to determine whether manipulating the infusion rate of a fixed dose of opioid alters its reinforcing effectiveness in humans. Twelve heroin-dependent participants (11 male, one female) completed the 2.5-week inpatient study. During test days, participants received $20 and a dose of drug (0 or 40 mg oxycodone administered intravenously over 2, 15, 30, 60, or 90 minutes) in random order during a morning sample session. Participants then worked for the sampled dose and/or money amount during an afternoon choice session by making finger presses on a computer mouse. Under these conditions, 40 mg oxycodone served as a reinforcer only when it was delivered over 2 and 15 minutes. Subjective ratings of drug liking, good effect, and high were similar to the self-administration results. Peak plasma levels of oxycodone generally occurred at the end of each infusion, eg, 2 minutes for the 2-minute infusion duration. Extended-release opioid medications are commonly prescribed for treating pain. The present results provide empirical support for the development of extended-release opioid medications that are difficult to convert into more rapid-acting forms. Specifically, these “abuse-deterrent formulations” could prevent patients from tampering with their medications to enhance their euphoric and reinforcing effects.