Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial

Abstract

Background: Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects.

Methods: We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity).

Results: Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high.

Conclusions: Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

Figures

Figure 1. Testing Schedule in a Randomized Cross-Over Trial Comparing Markers of Abuse Liability of Short- and Long-Acting Opioids in Chronic Pain Patients

Figure 2. Participant Dispositions in a Randomized Cross-Over Trial Comparing Markers of Abuse Liability of Short- and Long-Acting Opioids in Chronic Pain Patients

Figure 3. Sedation Levels over Time in a Randomized Cross-Over Trial Comparing Markers of Abuse Liability of Short- and Long-Acting Opioids in Chronic Pain Patients

(Sedation levels were measured as the PCAG dimension of the Addiction Research Center Inventory.) ○ Morphine ■ Hydrocodone ▲ Placebo

Figure 4. Visual Analog Scores for a) Drug Craving and b) Strong Desire to Take Drugs in a Randomized Cross-Over Trial Comparing Markers of Abuse Liability of Short- and Long-Acting Opioids in Chronic Pain Patients

(These questions are part of the four Drug-Liking questions used to assess abuse liability.)

Figure 5. Results of the Urge-to-Use Questions from the Cue-Reactivity Test in a Randomized Cross-Over Trial Comparing Markers of Abuse Liability of Short- and Long-Acting Opioids in Chronic Pain Patients