Neurobiology of craving, conditioned reward and relapse
Abstract
Chronic vulnerability to relapse is a formidable challenge for the treatment of drug addiction. The neurobiological basis of relapse and its prevention has, therefore, attracted major attention in addiction research. Current conceptualizations of addiction recognize craving as a central driving force for ongoing drug use, as well as for relapse following abstinence. Progress has been made in understanding experiential factors, neurocircuitry components and signaling mechanisms that mediate conditioned drug-seeking behaviour, craving and long-lasting susceptibility to relapse. Importantly, stress contributes to drug craving, and there is evidence for overlap between the neural and neuroendocrine mechanisms implicated in drug desire evoked by drug cues and stress. Recent research has substantially advanced our understanding of the neurobiological factors responsible for drug craving and relapse, with promising therapeutic implications.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Amygdala conditioning underlies cue-triggered craving that may precipitate relapse to drug seeking.
“The product of such conditioning in the amygdala (AMG) is thought to underlie the craving triggered by people, places, and things associated with drug use, which may precipitate relapse to drug-seeking behavior (Weiss, 2005).”
From Impulsivity, frontal lobes and risk for addiction (2009) · cites this paper as Weiss, 2005
Cites
Insensitivity to future consequences following damage to human prefrontal cortex
Bechara, A., Damasio, A. R., Damasio, H., & Anderson, S. W. (1994) · Cognition · doi:10.1016/0010-0277(94)90018-3 · Cited by 6,128 · see citing works
How does stress increase risk of drug abuse and relapse?
Sinha, R. (2001) · Psychopharmacology · doi:10.1007/s002130100917 · Cited by 1,505 · see citing works
Nucleus accumbens shell and core dopamine: differential role in behavior and addiction
Di Chiara, G. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00286-3 · Cited by 996 · see citing works
Differential control over cocaine-seeking behavior by nucleus accumbens core and shell
Ito, R., Robbins, T. W., & Everitt, B. J. (2004) · Nature Neuroscience · doi:10.1038/nn1217 · Cited by 501 · see citing works
Neurobiological evidence for hedonic allostasis associated with escalating cocaine use
Ahmed, S. H., Kenny, P. J., Koob, G. F., & Markou, A. (2002) · Nature Neuroscience · doi:10.1038/nn872 · Cited by 389 · see citing works
Challenges in the manipulation, assessment and interpretation of craving relevant variables
Tiffany, S. T., Carter, B. L., & Singleton, E. G. (2000) · Addiction · doi:10.1046/j.1360-0443.95.8s2.7.x · Cited by 221 · see citing works
Valdez, G. R., Zorrilla, E. P., Roberts, A. J., & Koob, G. F. (2003) · Alcohol · doi:10.1016/s0741-8329(03)00020-x · Cited by 186 · see citing works
Scaccianoce, S., Matrisciano, F., Del Bianco, P., Caricasole, A., Di Giorgi Gerevini, V., Cappuccio, I., Melchiorri, D., Battaglia, G., & Nicoletti, F. (2003) · Neuropharmacology · doi:10.1016/s0028-3908(03)00027-3 · Cited by 54 · see citing works
Preattentive processing of alcohol stimuli
Ingjaldsson, J. T., Thayer, J. F., & Laberg, J. C. (2003) · Scandinavian Journal of Psychology · doi:10.1111/1467-9450.00334 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neurobiologic advances from the brain disease model of addiction
Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1511480 · Cited by 2,008 · see citing works
Chronic stress, drug use, and vulnerability to addiction
Sinha, R. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1441.030 · Cited by 1,904 · see citing works
DSM-5 criteria for substance use disorders: recommendations and rationale
Hasin, D. S., O’Brien, C. P., Auriacombe, M., Borges, G., Bucholz, K., Budney, A., Compton, W. M., Crowley, T., Ling, W., Petry, N. M., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12060782 · Cited by 1,622 · see citing works
Avena, N. M., Rada, P., & Hoebel, B. G. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.04.019 · Cited by 1,358 · see citing works
Food cue reactivity and craving predict eating and weight gain: A meta-analytic review
Boswell, R. G., & Kober, H. (2016) · Obesity Reviews · doi:10.1111/obr.12354 · Cited by 703 · see citing works
Impulsivity, frontal lobes and risk for addiction
Crews, F. T., & Boettiger, C. A. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.04.018 · Cited by 679 · see citing works
“The product of such conditioning in the amygdala (AMG) is thought to underlie the craving triggered by people, places, and things associated with drug use, which may precipitate relapse to drug-seeking behavior (Weiss, 2005).”
BackgroundBrain activities associated with gaming urge of online gaming addiction
Ko, C.-H., Liu, G.-C., Hsiao, S., Yen, J.-Y., Yang, M.-J., Lin, W.-C., Yen, C.-F., & Chen, C.-S. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.09.012 · Cited by 666 · see citing works
Stress-induced reinstatement of drug seeking: 20 years of progress
Mantsch, J. R., Baker, D. A., Funk, D., Lê, A. D., & Shaham, Y. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.142 · Cited by 438 · see citing works
Bossert, J. M., Marchant, N. J., Calu, D. J., & Shaham, Y. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3120-y · Cited by 453 · see citing works
Sinha, R., Fox, H. C., Hong, K. A., Bergquist, K., Bhagwagar, Z., & Siedlarz, K. M. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.78 · Cited by 466 · see citing works
Witkiewitz, K., & Bowen, S. (2010) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0019172 · Cited by 453 · see citing works
REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?
Heilig, M., Egli, M., Crabbe, J. C., & Becker, H. C. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2009.00194.x · Cited by 435 · see citing works
The role of stress in addiction relapse
Sinha, R. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0050-6 · Cited by 423 · see citing works
Serre, F., Fatseas, M., Swendsen, J., & Auriacombe, M. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.12.024 · Cited by 389 · see citing works
Bickel, W. K., Koffarnus, M. N., Moody, L., & Wilson, A. G. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.013 · Cited by 386 · see citing works
Andersen, S. L., & Teicher, M. H. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.09.009 · Cited by 326 · see citing works
Modeling stress and drug craving in the laboratory: implications for addiction treatment development
Sinha, R. (2009) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00134.x · Cited by 314 · see citing works
Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder
Wang, G., Geliebter, A., Volkow, N. D., Telang, F. W., Logan, J., Jayne, M. C., Galanti, K., Selig, P. A., Han, H., Zhu, W., et al. (2011) · Obesity · doi:10.1038/oby.2011.27 · Cited by 313 · see citing works
Boileau, I., Dagher, A., Leyton, M., Welfeld, K., Booij, L., Diksic, M., & Benkelfat, C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4370-06.2007 · Cited by 222 · see citing works
Witkiewitz, K., Lustyk, M. K. B., & Bowen, S. (2013) · Psychology of Addictive Behaviors · doi:10.1037/a0029258 · Cited by 207 · see citing works
Zhao, Y., Dayas, C. V., Aujla, H., Baptista, M. A. S., Martin-Fardon, R., & Weiss, F. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2384-06.2006 · Cited by 192 · see citing works
Self-citationRecommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus
Dematteis, M., Auriacombe, M., D’Agnone, O., Somaini, L., Szerman, N., Littlewood, R., Alam, F., Alho, H., Benyamina, A., Bobes, J., et al. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1409722 · Cited by 141 · see citing works
Martel, M. O., Dolman, A. J., Edwards, R. R., Jamison, R. N., & Wasan, A. D. (2014) · The Journal of Pain · doi:10.1016/j.jpain.2013.09.014 · Cited by 137 · see citing works
Nair, S. G., Adams-Deutsch, T., Epstein, D. H., & Shaham, Y. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.05.003 · Cited by 112 · see citing works
Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients
Wasan, A. D., Butler, S. F., Budman, S. H., Fernandez, K., Weiss, R. D., Greenfield, S. F., & Jamison, R. N. (2009) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e318193a6c4 · Cited by 109 · see citing works
Priddy, S. E., Howard, M. O., Hanley, A. W., Riquino, M. R., Friberg-Felsted, K., & Garland, E. L. (2018) · Substance Abuse and Rehabilitation · doi:10.2147/sar.s145201 · Cited by 101 · see citing works
The Influence of Emotion Regulation on Decision-making under Risk
Martin, L. N., & Delgado, M. R. (2011) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2011.21618 · Cited by 105 · see citing works
Witkiewitz, K., Bowen, S., & Donovan, D. M. (2011) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0022282 · Cited by 94 · see citing works
Endocannabinoid-mediated synaptic plasticity and addiction-related behavior
Sidhpura, N., & Parsons, L. H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.034 · Cited by 92 · see citing works
Klauss, J., Anders, Q. S., Felippe, L. V., Nitsche, M. A., & Nakamura-Palacios, E. M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00716 · Cited by 80 · see citing works
Feed-forward mechanisms: Addiction-like behavioral and molecular adaptations in overeating
Alsiö, J., Olszewski, P. K., Levine, A. S., & Schiöth, H. B. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.01.002 · Cited by 81 · see citing works
Shi, J., Li, S.-X., Zhang, X.-L., Wang, X., Foll, B. L., Zhang, X.-Y., Kosten, T. R., & Lu, L. (2009) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990902933878 · Cited by 52 · see citing works
Zhang, F., Zhou, W., Liu, H., Zhu, H., Tang, S., Lai, M., & Yang, G. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.06.008 · Cited by 51 · see citing works
Galloway, G. P., Singleton, E. G., The Methamphetamine Treatment Project Corporate Authors, Anglin, M. D., Rawson, R. A., Patricia, M.-C., Joseph, B., Richard, B., Alison Hamilton, B., Cynthia, B., et al. (2008) · Substance Abuse: Research and Treatment · doi:10.4137/sart.s775 · Cited by 24 · see citing works
On the early-life origins of vulnerability to opioid addiction
Levis, S. C., Bentzley, B. S., Molet, J., Bolton, J. L., Perrone, C. R., Baram, T. Z., & Mahler, S. V. (2019) · doi:10.1101/716522 · Cited by 3 · see citing works
- Authors
- Weiss, F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Weiss, Friedbert
- ORCID
- Weiss, Friedbert
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 5
- Issue
- 1
- Pages
- 9-19
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2054971111
- Cited by
- 411
- References
- 9
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 9 · 2023: 15 · 2022: 7 · 2021: 15 · 2020: 19 · 2019: 15 · 2018: 15 · 2017: 13 · 2016: 17 · 2015: 18 · 2014: 19 · 2013: 15 · 2012: 27
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA 10531, AA014351, R01AA010531, AA-06420, R01AA014351)
- National Institute on Drug Abuse (DA07348, DA-08467, R01DA017097, R01DA008467, DA017097)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- drug craving, relapse, drug addiction, conditioned reward, drug-seeking behavior, stress, neuroendocrine mechanisms, drug cues, neurocircuitry, relapse prevention
- MeSH terms
- Animals, Brain, Conditioning, Psychological, Conditioning, Classical, Humans, Neurobiology, Recurrence, Reward, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review