Responsiveness to Drug Cues and Natural Rewards in Opiate Addiction: Associations With Later Heroin Use
Abstract
CONTEXT: Although drug cues reliably activate the brain's reward system, studies rarely examine how the processing of drug stimuli compares with natural reinforcers or relates to clinical outcomes. OBJECTIVES: To determine hedonic responses to natural and drug reinforcers in long-term heroin users and to examine the utility of these responses in predicting future heroin use. DESIGN: Prospective design examining experiential, expressive, reflex modulation, and cortical/attentional responses to opiate-related and affective stimuli. The opiate-dependent group was reassessed a median of 6 months after testing to determine their level of heroin use during the intervening period. SETTING: Community drug and alcohol services and a clinical research facility. PARTICIPANTS: Thirty-three opiate-dependent individuals (mean age, 31.6 years) with stabilized opiate-substitution pharmacotherapy and 19 sex- and age-matched healthy non-drug users (mean age, 30 years). MAIN OUTCOME MEASURES: Self-ratings, facial electromyography, startle-elicited postauricular reflex, and event-related potentials combined with measures of heroin use at baseline and follow-up. RESULTS: Relative to the control group, the opiate-dependent group rated pleasant pictures as less arousing and showed increased corrugator activity, less postauricular potentiation, and decreased startle-elicited P300 attenuation while viewing pleasant pictures. The opiate-dependent group rated the drug-related pictures as more pleasant and arousing, and demonstrated greater startle-elicited P300 attenuation while viewing them. Although a startle-elicited P300 amplitude response to pleasant (relative to drug-related) pictures significantly predicted regular (at least weekly) heroin use at follow-up, subjective valence ratings of pleasant pictures remained the superior predictor of use after controlling for baseline craving and heroin use. CONCLUSIONS: Heroin users demonstrated reduced responsiveness to natural reinforcers across a range of psychophysiological measures. Subjective rating of pleasant pictures robustly predicted future heroin use. Our findings highlight the importance of targeting anhedonic symptoms within clinical treatment settings.
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Opiate abuse is associated with altered cortical blood flow, grey matter loss, and impaired connectivity.
“Opiate abuse has been associated with changes in cortical blood flow (Fu et al., 2008; Lubman et al., 2009), grey matter loss (Lyoo et al., 2006) and impaired connectivity (Schmidt et al., 2015).”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Lubman et al., 2009
Opiate-dependent participants show decreased arousal ratings and physiological measures of reward motivation to pleasant pictures relative to drug-cue images.
“In a study using multi-modal psychophysiological measurements, Lubman and colleagues [156] reported decreased arousal ratings and physiological measures of reward motivation to pleasant pictures relative to drug-cue images in opiate-dependent participants.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [156]
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- Authors
- Lubman, D. I., Yücel, M., Kettle, J. W. L., Scaffidi, A., MacKenzie, T., Simmons, J. G., & Allen, N. B.
- Affiliations
- Orygen (AU)
- The University of Melbourne (AU)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-02-01
- Volume
- 66
- Issue
- 2
- Pages
- 205
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2006014464
- Cited by
- 176
- References
- 55
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 13 · 2014: 18 · 2013: 12 · 2012: 13
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- heroin addiction, opioid use disorder, drug cue reactivity, natural reward, hedonic response, anhedonia, P300, startle response, corrugator supercilii, facial electromyography, opioid substitution therapy, craving
- MeSH terms
- Adult, Affective Symptoms, Alcoholism, Arousal, Attention, Cerebral Cortex, Cues, Electromyography, Emotions, Female, Follow-Up Studies, Heroin Dependence, Humans, Male, Middle Aged, Motivation, Narcotics, Recurrence, Reward, Risk Factors, Reflex, Startle, Comorbidity, Event-Related Potentials, P300, Young Adult
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