Trial reportDrug and alcohol dependence2025
Inter-individual divergence in thresholds for detecting opioid effects: Within-subject human laboratory evidence of a testable behavioral phenotype.
Trial report in Drug and alcohol dependence, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Reliable variability in subjective responses to parenteral hydromorphone administration: empirical confirmation of an opioid non-responder phenotype.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Nonpharmacological and pharmacological influences on opioid effects: A review of clinical research findings.The Journal of pharmacology and experimental therapeutics · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Variations in inter-individual response to opioid medications has not been well-investigated in prospective, empirical designs or in persons who have no learned experience with opioids or current pain conditions. These analyses categorized response to opioids during rigorous human laboratory experimental conditions. Healthy individuals (N = 75) with little to no prior opioid exposure completed a 5-day residential study wherein they received triple-blinded doses of placebo or oral hydromorphone (2mg, 4mg, 8mg). Outcomes included a series of general and specific visual analog scale (VAS) ratings completed by participants and blinded observers, physiological endpoints, and analgesic responses to laboratory-evoked pain. The lowest dose at which participants endorsed > 20 point change in self-reported "Drug Effect" VAS ratings from baseline was used to define the following opioid sensitivity thresholds: 2mg ("Low Threshold", N = 9), 4mg ("Medium"; N = 29), and 8mg ("High", N = 14); a "No Threshold" group (N = 31) did not endorse any effects at any dose. Main effects of sensitivity threshold existed for most participant-reported responses and conformed to threshold categories in dose-dependent ways. In contrast, no main effects of sensitivity threshold were observed for blinded observer ratings, physiological endpoints, or evoked analgesic responses, such that hydromorphone produced dose-dependent opioid agonist effects for all participants that diverged from their self-reported experience. These data provide the most granular assessment of inter-individual differences in opioid response among persons with little or no lifetime opioid exposure or existing pain condition. All participants experienced dose-dependent changes in opioid agonist responses, yet their self-awareness of these effects varied and 30 % of participants endorsed no awareness of opioid exposure at any dose. These data demonstrate a consistent and reliable divergence between the subjective experience of opioids from rigorously-assessed physiological, observable, and analgesic responses. Testable implications of these outcomes are discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.