Likeability and Abuse Liability of Commonly Prescribed Opioids

Wightman, Rachel; Perrone, Jeanmarie; Portelli, Ian; Nelson, Lewis S.

doi:10.1007/s13181-012-0263-x

Cited by 116 publications

(75 citation statements)

References 16 publications

(31 reference statements)

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“…Pain remains a significant clinical problem (Gaskin and Richard, 2012), and m opioid receptor agonists remain the drugs of choice for treating moderate to severe pain, despite the high abuse liability of these drugs and a current epidemic of fatal drug overdoses (Wightman et al, 2012;Volkow et al, 2014). Consequently, there is a pressing need to identify alternative pharmacotherapies with reduced adverse effects that currently limit the clinical use of m opioid receptor agonists.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Minervini¹,

Dahal²,

France³

2016

J Pharmacol Exp Ther

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Pain is a significant clinical problem, and there is a need for more effective treatments with reduced adverse effects that currently limit the use of m opioid receptor agonists. Synthetic k opioid receptor agonists have no abuse liability and well-documented antinociceptive effects; however, adverse effects (diuresis, dysphoria) preclude their use in the clinic. Combining k opioids with nonopioid drugs (cannabinoid receptor agonists) allows for smaller doses of each drug to produce antinociception. This study tested whether a potentially useful effect of the k opioid receptor agonist 2-Cumulative dose-response functions were determined in eight male Sprague-Dawley rats for spiradoline (0.032-32.0 mg/kg, i.p.) and CP55940 (0.0032-1.0 mg/kg, i.p.) for antinociception, hypothermia, food-maintained responding, and diuresis. Alone, each drug dose dependently increased tail withdrawal latencies from 50°C water, decreased body temperature by ∼4°C, and eliminated food-maintained responding. Spiradoline, but not CP55940, significantly increased urine output at doses that eliminated responding. Smaller doses of spiradoline and CP55940 in mixtures (3:1, 1:1, and 1:3 spiradoline:CP55940) had effects comparable to those observed with larger doses of either drug administered alone: the interaction was additive for antinociception and additive or greater than additive for hypothermia and food-maintained responding. Collectively, these data fail to provide support for the use of these mixtures for treating acute pain; however, k opioid/cannabinoid mixtures might be useful for treating pain under other conditions (e.g., chronic pain), but only if the adverse effects of both drugs are not enhanced in mixtures.

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Section: Discussionmentioning

confidence: 99%

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Minervini¹,

Dahal²,

France³

2016

J Pharmacol Exp Ther

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“…It has been used for almost 100 years in medicine, mostly for the treatment of various forms of pain (Kalso, 2005;Wightman et al, 2012). Although oxycodone has excellent efficacy as an analgesic, it also produces tolerance and dependence, similar to other opioid compounds (Mars et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

Wiebelhaus

Walentiny

Beardsley

2015

Journal of Pharmacology and Experimental Therapeutics

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Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose-and time-dependent effects of acute and repeated oxycodone administration in a frequencyrate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and ratedecreasing effects maintained by ICSS similar to m-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose-and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects.

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“…Morphine is historically the "base comparison" opioid, and with good reason [172]. The drug has been around for as long as any other opioid and has excellent safety and efficacy when used appropriately.…”

Section: Morphinementioning

confidence: 99%

Management of Pain in the Emergency Department

Thomas

2013

ISRN Emergency Medicine

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Since pain is a primary impetus for patient presentation to the Emergency Department (ED), its treatment should be a priority for acute care providers. Historically, the ED has been marked by shortcomings in both the evaluation and amelioration of pain. Over the past decade, improvements in the science of pain assessment and management have combined to facilitate care improvements in the ED. The purpose of this review is to address selected topics within the realm of ED pain management. Commencing with general principles and definitions, the review continues with an assessment of areas of controversy and advancing knowledge in acute pain care. Some barriers to optimal pain care are discussed, and potential mechanisms to overcome these barriers are offered. While the review is not intended as a resource for specific pain conditions or drug information, selected agents and approaches are mentioned with respect to evolving evidence and areas for future research.

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Likeability and Abuse Liability of Commonly Prescribed Opioids

Cited by 116 publications

References 16 publications

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

Management of Pain in the Emergency Department

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