Opioid abusers' ability to differentiate an opioid from placebo in laboratory challenge testing.
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<0.0001). Non-qualifiers' failure to differentiate oxycodone versus placebo was evident for subject and observer ratings.


CONCLUSIONS
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.
Johns Hopkins University School of Medicine, Bayview Campus, Behavioral Pharmacology Research Unit, 5510 Nathan Shock Drive, Baltimore, MD 21224, United States. Antoine@jhmi.edu
Denis G
DG
Antoine
Eric C
EC
Strain
D Andrew
DA
Tompkins
George E
GE
Bigelow
D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000494:pharmacology*; D018592:Cross-Over Studies; D004192:Discrimination, Psychological / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005059:Euphoria / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000523:psychology*; D010098:Oxycodone / Q000494:pharmacology; D010919:Placebos; D011680:Pupil / Q000187:drug effects; D055815:Young Adult
D000701:Analgesics, Opioid; D009294:Narcotics; D010919:Placebos; D010098:Oxycodone
Abuse liability; Discrimination; Opioids; Placebo; Qualification