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Cited by 81Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on Behavior

Laboratory-induced cue reactivity among individuals with prescription opioid dependence

Open access
Back, Sudie E., Gros, Daniel F., McCauley, Jenna L., Flanagan, Julianne C., Cox, Elizabeth, Barth, Kelly S., Brady, Kathleen T.·2014·Addictive Behaviors
DOI 10.1016/j.addbeh.2014.04.007PMC PMC4059191
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Abstract

Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence.

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Registry

Crossref · 10.1016/j.addbeh.2014.04.007

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 27 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Control participants did not show significant pre- to post-cue changes on any subjective rating.

    “The control group did not demonstrate significant changes on any of the subjective measures.”
    Quote in the paperSubstantial claim
  • Findingown data

    In participants with prescription opioid dependence, the drug cue paradigm produced a significant increase from pre-cue to post-cue in stress.

    “the PO group evidenced significant pre- to post-cue changes on subjective ratings of craving (Figure 1), stress (Figure 2), difficulty resisting use, and anger (ts > 2.8; ps < .05).”
    Quote in the paperSubstantial claim
  • Findingown data

    Both participants with prescription opioid dependence and controls showed a significant increase from pre-cue to post-cue in mean arterial pressure in response to the drug cue.

    “Both the PO and control groups demonstrated increased MAP and GSR in response to the drug cue (ts > 4.9; ps < .01).”
    Quote in the paperSubstantial claim
  • Findingown data

    In participants with prescription opioid dependence, the drug cue paradigm produced a significant increase from pre-cue to post-cue in anger.

    “the PO group evidenced significant pre- to post-cue changes on subjective ratings of craving (Figure 1), stress (Figure 2), difficulty resisting use, and anger (ts > 2.8; ps < .05).”
    Quote in the paperSubstantial claim
  • Findingown data

    Participants with prescription opioid dependence, but not controls, showed a significant increase from pre-cue to post-cue in heart rate in response to the drug cue.

    “The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels.”
    • Also stated in: § Effects of Drug Cue on Physiological Reactivity · boosted
      “However, the PO group (t = 3.3, p < .01), but not the control group (t = 1.9; p > .05), demonstrated increased HR in response to the drug cue. This HR finding was further supported by a significant group effect on post-cue HR in the ANCOVA (F = 4.4; p < .05).”
    Quote in the paperSubstantial claim
  • May combine two claims. 16
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Findingown data

    The new paradigm produced negative affect as well as craving in prescription-opioid-dependent participants.

    “Subjective results also show that the newly developed paradigm elicited negative affect in addition to craving among PO dependent individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Control participants' stress, anger, and sadness either decreased or did not change after cue exposure.

    “Stress, anger, and sadness either improved or stayed the same following cue administration among controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both prescription-opioid and control participants had significant increases in mean arterial pressure and galvanic skin response from before to after cue exposure.

    “Participants in both the PO and control group demonstrated significant pre- to post-cue increases in MAP and GSR.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At baseline, prescription-opioid-dependent participants reported more negative affect, such as stress and anger, and more craving than controls.

    “At baseline, PO dependent individuals presented with significantly more negative affect (e.g., stress, anger) and craving.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    From before to after cue exposure, prescription-opioid-dependent participants had larger increases than controls in craving, stress, anger, and inability to resist using.

    “As expected, the PO group evidenced significantly greater increases in pre- to post-cue craving, stress, anger, and inability to resist using in response to the drug cue paradigm compared to the control group.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In a treatment-seeking sample of individuals with prescription opioid dependence, 74% had relapsed by week 16 and 91% by week 24.

    “At week 16, 74% of participants had relapsed and by week 24, 91% had relapsed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Weiss et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exposure to drug-related cues, compared with neutral cues, increases craving and produces changes in mood and physiological measures.

    “Previous laboratory studies have shown that exposure to drug-related cues, as compared to neutral cues, increases craving and induces changes in mood states and physiological measures (Carter & Tiffany, 1999; Shi et al., 2009; Yu et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Carter & Tiffany, 1999

      Not checked in the free run.

    • cites Shi et al., 2009 source

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    • cites Yu et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    At baseline, participants with prescription opioid dependence had higher subjective ratings than controls for stress, craving, difficulty resisting use, anger, willingness to pay to use, and state anxiety, and lower happiness.

    “These findings demonstrated significantly higher subjective ratings for stress (Figure 1), craving (Figure 2), difficulty resisting use, anger, amount willing to pay to use, and state anxiety (STAI) as well as significant lower happiness in the PO group compared to the control group (Fs > 3.9; ps < .055).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Salivary cortisol was assayed in duplicate using a high-sensitivity enzyme immunoassay with an intra-assay coefficient of variation of 3.35% to 3.65% and a sensitivity below 0.003 ug/dL.

    “Samples were assayed in duplicate using a high sensitivity salivary cortisol enzyme immunoassay system that has an intra-assay precision (coefficient of variation, CV) of 3.35% – 3.65% with a sensitivity of <0.003 ug/dL (Salimetrics LLC).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Conditioned stimuli play a critical role in maintaining drug-seeking behavior and relapse after periods of abstinence.

    “Thus, conditioned stimuli play a critical role in sustaining ongoing drug-seeking behavior and relapse after periods of abstinence (Childress et al., 1988; O’Brien et al., 1998; Sinha et al., 2000; Stewart, 2003).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Childress et al., 1988

      Not checked in the free run.

    • cites O’Brien et al., 1998

      Not checked in the free run.

    • cites Sinha et al., 2000 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Participants were admitted to the hospital overnight before testing to control for extraneous variables such as sleep and caffeine intake that could affect reactivity.

    “Participants were admitted to the hospital at 2000h the evening prior to testing to allow for the control of extraneous variables (e.g., sleep, caffeine intake) that could potentially affect reactivity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The prescription opioid and control groups differed in education and employment status, but no other demographic differences were observed.

    “As expected, two-variable χ2 tests revealed group differences in education and employment status (χ2s > 4.9; ps < .05). No other demographic differences were observed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Three days of abstinence from alcohol and other substances, except caffeine and nicotine, were required before admission and verified by self-report, breathalyzer, and urine drug screen.

    “Three days of abstinence from alcohol and other substances (except caffeine and nicotine), as evidence by self-report, breathalyzer and urine drug screen, were required prior to admission for the overnight stay.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    At baseline, participants with prescription opioid dependence had higher Addiction Severity Index subscale scores for drug use, legal status, and psychiatric symptoms than controls.

    “One-way analyses of variance (ANOVA) revealed significantly higher ASI subscale scores for drug use, legal status, and psychiatric symptoms among the PO group, as compared to controls (Fs > 6.2; ps < .05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    HPA measures were consistent with participants' subjective and physiological responses, which supports the validity of the drug cue paradigm.

    “Further, these findings suggest that measures of HPA function were consistent with participants’ subjective and physiological responses, lending further support to the validity of the drug cue paradigm developed here.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cue reactivity paradigms have been used successfully to identify neural substrates and networks involved in craving for nicotine, cocaine, and alcohol.

    “As an example of potential future applications for the current paradigm, cue reactivity paradigms have been successfully used to elucidate neural substrates and networks implicated in the craving response for an array of substances including nicotine, cocaine, and alcohol (Cunningham & Anastasio, 2013; Engelmann et al., 2012; Lou et al., 2012; Mainz et al., 2012; Schacht, Anton, & Myrick, 2013),”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cunningham & Anastasio, 2013

      Not checked in the free run.

    • cites Engelmann et al., 2012 source

      Not checked in the free run.

    • cites Lou et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Negative affect and craving predict relapse in other substance-dependent groups.

    “These responses are often identified as interrelated (Schlauch, Gwynn-Shapiro, Stasiewicz, Molnar, & Lang, 2013) and are consistent predictors of relapse among other substance dependent populations (Hendershoot, Witkiewitz, George, & Marlatt, 2011; Li et al., 2012).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hendershoot, Witkiewitz, George, & Marlatt, 2011

      Not checked in the free run.

    • cites Li et al., 2012

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cue reactivity paradigms have made major contributions to addiction research across alcohol, cocaine, heroin, and nicotine.

    “Cue reactivity paradigms have contributed significantly to advancements in addictions research for a variety of substances, including alcohol, cocaine, heroin, and nicotine (Carter & Tiffany, 1999a,b).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Carter & Tiffany, 1999a,b

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Negative affect and craving are often considered interrelated.

    “These responses are often identified as interrelated (Schlauch, Gwynn-Shapiro, Stasiewicz, Molnar, & Lang, 2013) and are consistent predictors of relapse among other substance dependent populations (Hendershoot, Witkiewitz, George, & Marlatt, 2011; Li et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schlauch, Gwynn-Shapiro, Stasiewicz, Molnar, & Lang, 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In earlier drug cue paradigm studies, post-cue cortisol increases indicate a stress response that correlates with drug craving and predicts future relapse.

    “In prior drug cue paradigm research, post-cue elevations in cortisol have been found to be indicative of a stress response that is correlated with drug craving, and predictive of future relapse (Back et al., 2010; Fatseas et al., 2011).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Back et al., 2010 source

      Not checked in the free run.

    • cites Fatseas et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Developing and validating a prescription-opioid-specific cue paradigm has potential to extend drug abuse research to prescription opioid use disorders.

    “The development and validation of a PO-specific cue paradigm has potential utility in extending advances in drug abuse research to the study of PO use disorders.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Normative IAPS data indicate that pictures of drug-related behaviors and cocaine paraphernalia receive moderate arousal ratings and are therefore likely to arouse most participants, including non-using healthy controls.

    “In fact, normative data on the International Affective Picture System (Lang, Ohman, & Vaitl, 1988), involving a wide range of affective pictures with valence and arousal ratings, suggest that pictures of drug related behaviors and cocaine paraphernalia receive moderate arousal ratings”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Lang, Ohman, & Vaitl, 1988

      Not checked in the free run.

    • cites Cuthbert, Bradley, & Lang, 1996

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because all participants had abstained from prescription opioids for at least three days, mild withdrawal symptoms may have affected reactivity.

    “All participants had abstained from PO use for at least three days prior to their participation in the study. Acute abstinence has been noted as limitation of cue paradigms for other substances (e.g., Adams & Munafo, 2013); experience of mild PO withdrawal symptoms may have influenced reactivity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Adams & Munafo, 2013

      Not checked in the free run.

23 of 23

  • The paper relies on this without support.

    No studies have examined cue reactivity among individuals with prescription opioid dependence, and no prescription opioid-specific drug cue paradigm has been developed.

    “To our knowledge, there have not been any studies examining cue reactivity among individuals with PO dependence. This critical gap in the literature is likely due to the fact that no drug cue paradigm for POs has been developed.”

  • The paper relies on this without support.

    The study is the first to develop and validate a cue paradigm specific to prescription opioids.

    “To our knowledge, this is the first study to develop and validate a drug cue paradigm specific to prescription opioids; that is, containing triggers that are directly address POs (e.g., a bottle of opioid pills, images of pharmacies, handling a pill crusher).”

  • The paper relies on this without support.

    Prescription opioid misuse, abuse, and dependence are epidemic and increasing.

    “In light of the continuing epidemic rise in misuse, abuse, and dependence on POs, the development of cue reactivity paradigms that are specific to POs is needed to help enhance assessment, treatment and relapse prevention.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Exposure to drug-related cues mediates symptoms of craving in opioid use disorder and may be linked with increased cortisol responses.

    “Exposure to drug-related cues mediates the symptoms of craving in OUD (44–49) and may be linked with increased cortisol responses (50), consistent with the neuroendocrine underpinnings of craving as described in Figure 2 .”

    From Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice (2019) · cites this paper as [45]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure numbers for stress and craving are reversed

    Minor

    The results first identify Figure 1 as stress and Figure 2 as craving, then assign those figure numbers the other way around.

1 of 1

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Related

Authors
Back, S. E., Gros, D. F., McCauley, J. L., Flanagan, J. C., Cox, E., Barth, K. S., & Brady, K. T.
Affiliations
  • Medical University of South Carolina (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Back, Sudie E.
ORCID
Venue
Addictive Behaviors
Publisher
Elsevier BV
Published
2014-08
Volume
39
Issue
8
Pages
1217-1223
ISSN
0306-4603 (ISSN-L)
DOI
10.1016/j.addbeh.2014.04.007
PMC
PMC4059191
OpenAlex
W2033010168
Semantic Scholar
22a38664167bf5e69e09624846b5b06a287ea9a5
Cited by
81
References
69
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 10 · 2021: 4 · 2020: 47 · 2019: 3 · 2018: 6 · 2017: 2 · 2015: 3
FWCI
1.65
Type
journal article
Language
en
Open access
Locations
  • Addictive Behaviors (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • U.S. Department of Veterans Affairs (RR029882)
  • National Institutes of Health (RR029882)
  • National Institute on Drug Abuse (DA021228, HD055885, K12 DA031974, K23DA021228, R25DA020537, K12DA031794)
  • National Center for Research Resources (UL1RR029882)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD055885)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
prescription opioid dependence, drug cue reactivity, craving, relapse risk, physiological arousal, salivary cortisol, heart rate, skin conductance, blood pressure, paraphernalia, OxyContin
MeSH terms
Adult, Blood Pressure, Cues, Emotions, Female, Galvanic Skin Response, Heart Rate, Humans, Hydrocortisone, Male, Middle Aged, Opioid-Related Disorders, Surveys and Questionnaires, Saliva, Stress, Psychological, Case-Control Studies, Behavior, Addictive, Prescription Drugs, Young Adult, Craving

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