Open Access Open Access  Restricted Access Subscription or Fee Access

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

Sandra D. Comer, PhD, Judy B. Ashworth, MD, Maria A. Sullivan, MD, PhD, Suzanne K. Vosburg, PhD, Phillip A. Saccone, BS, Richard W. Foltin, PhD


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.


abuse deterrent, abuse liability, humans, opiates, oxycodone, rate of infusion, reinforcing effects, self-administration

Full Text:



Substance Abuse and Mental Health Services Administration (SAMHSA): Results from the 2007 National Household Survey on Drug Use and Health: National findings, 2008.

Manchikanti L, Singh A: Therapeutic opioids: A ten-year perspective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids. Pain Physician. 2008; 11 (Opioid Special Issue): S63-S88.

Katz N, Fernandez K, Chang A, et al.: Internet-based survey of nonmedical prescription opioid use in the United States. Clin J Pain. 2008; 24: 528-535.

Balster RL, Schuster CR: Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. J Exp Anal Behav. 1973; 20: 119-129.

Panlilio LV, Goldberg SR, Gilman JP, et al.: Effects of delivery rate and non-contingent infusion of cocaine on cocaine selfadministration in rhesus monkeys. Psychopharmacology. 1998; 137: 253-258.

Woolverton WL, Wang Z: Relationship between injection duration, transporter occupancy, and reinforcing strength of cocaine. Eur J Pharmacol. 2004; 486: 251-257.

Lile JA, Wang Z, Woolverton WL, et al.: The reinforcing efficacy of psychostimulants in rhesus monkeys: The role of pharmacokinetics and pharmacodynamics. J Pharmacol Exp Ther. 2003; 307(1): 356-366.

Woolverton WL, Ranaldi R, Wang Z, et al.: Reinforcing strength of a novel dopamine transporter ligand: Pharmacodynamic and pharmacokinetic mechanisms. J Pharmacol Exp Ther. 2002; 303: 211-217.

Abreu ME, Bigelow GE, Fleisher L, et al.: Effect of injection speed on responses to cocaine and hydromorphone in humans. Psychopharmacology. 2001; 154: 76-84.

Nelson RA, Boyd SJ, Ziegelstein RC, et al.: Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans. Drug Alcohol Depend. 2006; 82: 19-24.

de Wit H, Bodker B, Ambre J: Rate of increase of plasma drug level influences subjective response in humans. Psychopharmacology. 1992; 107(2-3): 352-358.

de Wit H, Dudish S, Ambre J: Subjective and behavioral effects of diazepam depend on its rate of onset. Psychopharmacology. 1993; 112(2-3): 324-330.

Mumford GK, Evans SM, Fleishaker JC, et al.: Alprazolam absorption kinetics affects abuse liability. Clin Pharmacol Ther. 1995; 57: 356-365.

Roset PN, Farre M, de la Torre R, et al.: Modulation of rate of onset and intensity of drug effect reduces abuse potential in healthy males. Drug Alcohol Depend. 2001; 64: 285-298.

Marsch LA, Bickel WK, Badger GJ, et al.: Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans. J Pharmacol Exp Ther. 2001; 299: 1056-1065.

Farre M, Cami J: Pharmacokinetic considerations in abuse liability evaluation. Br J Addict. 1991; 86: 1601-1606.

Comer SD, Sullivan MA, Whittington RA, et al.: Abuse liability of prescription opioids compared to heroin in morphinemaintained heroin abusers. Neuropsychopharmacology. 2008; 33: 1179-1191.

Zacny JP, Lichtor SA: Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers. Psychopharmacology. 2008; 196(1): 105-116.

Walsh SL, Nuzzo PA, Lofwall MR, et al.: The relative abuse liability of oral oxycodone, hydrocodone, and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend. 2008; 98: 191-202.

Hays L, Kirsh KL, Passik SD: Seeking drug treatment for Oxycontin abuse: A chart review of consecutive admissions to a substance abuse treatment facility in Kentucky. J Natl Compr Canc Netw. 2003; 1(3): 1-6.

Comer SD, Collins ED, Fischman MW: Choice between money and intranasal heroin in morphine-maintained humans. Behav Pharmacol. 1997; 8: 667-690.

Comer SD, Collins ED, Wilson ST, et al.: Effects of an alternative reinforcer on i.v. heroin self-administration by humans. Eur J Pharmacol. 1998; 345(1): 13-26.

Comer SD, Collins ED, MacArthur RB, et al.: Comparison of intranasal and intravenous heroin self-administration by morphine-maintained humans. Psychopharmacology. 1999; 143: 327-338.

Comer SD, Sullivan MA, Walker EA: Comparison of intravenous buprenorphine and methadone self-administration by recently detoxified heroin-dependent individuals. J Pharmacol Exp Ther. 2005; 315(3): 1320-1330.

Carise D, Leggett Dugosh K, McLellan AT, et al.: Prescription OxyContin abuse among patients entering addiction treatment. Am J Psychiatry. 2007; 164: 1750-1756.



  • There are currently no refbacks.