The results of this study demonstrated that ALO-01, whether taken orally whole as intended or tampered with by crushing and taken orally, had reduced desirability compared with MSS.

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL has the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided and then those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are discussed. These outcome measures include: (1) subjective effects (some of which comprise the primary outcome measures, including drug liking); (2) physiological responses; (3) drug self-administration behavior; and (4) cognitive and psychomotor performance. Prior to presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.

There is evidence that exteroceptive cues associated with drug administration elicit conditional compensatory responding (e.g., hyperalgesia in organisms with a history of morphine administration). Recently it has become apparent that, within each administration, interoceptive early-drug onset cues (DOCs) may become associated with the later, larger drug effect (intraadministration associations). The present experiments evaluated DOC-elicited conditional hyperalgesia in rats intravenously infused with morphine. The results indicated that DOC-elicited hyperalgesia contributes to tolerance to the analgesic effect of morphine, and such DOC-elicited hyperalgesia is an associative phenomenon, rather than a sensitized response to the opiate. The findings suggest that associative analyses of tolerance should acknowledge the conditional responding elicited by DOCs, and extinction-based addiction treatments should incorporate extinction of DOC-elicited conditional responding.

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Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials.