Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

Abstract

This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Insights from Preclinical Choice Models on Treating Drug Addiction

“…These preclinical choice procedures provide an explicit, albeit simplified, model of the clinical context in which behavioral allocation occurs between drug use and other activities maintained by nondrug reinforcers. Second, these preclinical results are consistent with human laboratory studies demonstrating dose-dependent increases in the choice of the abused drugs cocaine [32,33], methamphetamine [34,35], opiates [36], Δ-9-tetrahydrocannabinol [37], and tobacco cigarettes [38] relative to choice of a nondrug alternative (usually money). Lastly, these results show that simply introducing an alternative nondrug reinforcer attenuates the potency of abused drugs to function as reinforcers compared with their potency in other drug self-administration procedures that do not include a concurrently available alternative reinforcer.…”

Rapid dopamine transmission within the nucleus accumbens: Dramatic difference between morphine and oxycodone delivery

“…In particular, oxycodone is among the most commonly abused opioids (McCabe et al ., ,b). While there is no doubt that greater availability of this prescription drug has contributed to this rise in abuse, there is growing evidence suggesting that oxycodone may be more potent with respect to its ability to promote addictive behaviors (Stoops et al ., ; Comer et al ., ). For example, in the clinical realm, oxycodone administration to human heroin addicts, compared to other opioids, caused robust reinforcing effects with no increases in negative effects (Comer et al ., ).…”

“…oxycodone, hydrocodone and fentanyl) are tremendously effective for pain management and, while it was initially suggested that oxycodone is unlikely to be more addictive than morphine (Davis et al ., ), oxycodone is widely abused and is among the fastest growing drugs of abuse (Compton & Volkow, ). While this is certainly influenced by greater availability due to prescription use, recent studies suggest that oxycodone may have a higher potential to promote addiction‐related behaviors than other opioids, such as morphine (Stoops et al ., ; Comer et al ., ). However, little is known about how oxycodone and morphine differentially influence changes in brain function associated with drug abuse and addiction.…”

BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

“…Laws allowing the use of opioid analgesics in the management of non-cancerous, chronic pain led to the escalation of OXY use, and not unexpectedly its abuse (Manchikanti et al, 2010). Indeed, there is accumulating evidence that OXY is more addictive than morphine (Stoops et al, 2010; Comer et al, 2013). Opioid addiction in the United States accounted for nearly 19,000 overdose deaths in 2014 with OXY responsible for a majority of these fatalities (Center for Disease Control and Prevention, 2015).…”