Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Abstract

Background Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers. Methods Data were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo’s peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings. Results 61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p<.0001). Non-qualifiers’ failure to differentiate oxycodone versus placebo was evident for subject and observer ratings. Conclusion Different subjective responses to identical stimuli support the use of a qualification phase in abuse liability assessments. Further research should explore objective measures that may better account for these differences, determine optimal qualification criteria, and explore the developmental course of drug use. This study also documents certain opioid abusers fail to differentiate 30 mg of oxycodone from placebo, a phenomenon deserving further study.

Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model

“…This may partially explain the inconsistency that exists between patient reports of the opioid-sparing potential of THC and empirical research. Although this is the first opioid–cannabinoid administration study to examine the contribution of opioid responder status on outcomes, these results are consistent with prior laboratory evaluations that have found pronounced and clinically-meaningful individual differences in response to hydromorphone, heroin, and oxycodone [ 31 , 46 ]. The fact that effects were observed within subjective reports, abuse liability, and cognition, but not analgesia, suggests that opioid sensitivity may have multiple physiological and/or pharmacological mechanisms.…”

“…Participants were then classified as opioid responders or nonresponders. An opioid responder was defined as having >20-point difference between baseline and post-drug administration on the Drug Effects VAS scale during the hydromorphone + placebo session [ 46 ]. Next, analyses were repeated adding responder status as a covariate, and then sensitivity analyses of main effects were conducted within the opioid responder and nonresponder subgroups following the analytic plan described above.…”

Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

“…A crossover design was employed to control for within-subject variability, and subjects were required to have a history of recreational drug abuse for eligibility. Additionally, a qualification phase was implemented to ensure the study did not enroll a substantial percentage of nonresponders (patients not able to discriminate between active drug and placebo) [ 26 , 29 ]. Results from this abuse potential study are in line with results from in vitro manipulation and extraction studies and pharmacokinetic studies of hydrocodone ER, and confirm the abuse-deterrent properties of this hydrocodone ER formulation which limits rapid release of drug when finely crushed, significantly reducing drug-liking compared with hydrocodone IR.…”

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype–genotype assessment

“…Only 12% of the estimated >10 million persons in the United States who report lifetime use of an opioid develop opioid use disorder (OUD), 1 suggesting only a subgroup of persons who are exposed to opioids develop problematic opioid use behaviours 2 . To date, there have been limited evaluations of opioid response profiles; however, existing clinical reports 3 and laboratory studies 4–7 suggest that some individuals demonstrate dose‐dependent responses to opioids whereas other individuals do not differentiate even high doses of opioids from placebo across a variety of patient‐reported, observed, and physiological outcomes (even when offered money for correctly differentiating between an opioid and a placebo) 5,8 . These reports are primarily based upon persons who have a history of OUD, which is a population that has a demonstrated ability to interoceptively detect opioids.…”

“… 2 To date, there have been limited evaluations of opioid response profiles; however, existing clinical reports 3 and laboratory studies 4 , 5 , 6 , 7 suggest that some individuals demonstrate dose‐dependent responses to opioids whereas other individuals do not differentiate even high doses of opioids from placebo across a variety of patient‐reported, observed, and physiological outcomes (even when offered money for correctly differentiating between an opioid and a placebo). 5 , 8 These reports are primarily based upon persons who have a history of OUD, which is a population that has a demonstrated ability to interoceptively detect opioids. Much less is understood about the experience of opioids at the time of initiation, prior to development of acute or sustained tolerance.…”