Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Remission from addiction: erasing the wrong circuits or making new ones?

Nature Reviews Neuroscience volume 26, pages 115–130 (2025)Cite this article

Subjects

Abstract

Chronic relapse is a hallmark of substance-use disorders (SUDs), but many people with SUDs do recover and eventually enter remission. Many preclinical studies in this field aim to identify interventions that can precipitate recovery by reversing or erasing the neuronal circuit changes caused by chronic drug use. A better understanding of remission from SUDs can also come from preclinical studies that model factors known to influence recovery in humans, such as the negative consequences of drug use and positive environmental influences. In this Perspective we discuss human neuroimaging studies that have provided information about recovery from SUDs and highlight mechanisms identified in preclinical studies — such as the reconfiguration of neuronal circuits — that could contribute to remission. We also analyse how studies of memory and forgetting can provide insights into the mechanisms of remission. Overall, we propose that remission can be driven by the introduction of new neuronal changes (which outcompete those induced by drugs) as well as by the erasure of drug-induced changes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Evolution of drug use.
Fig. 2: Drug intake, remission and social support involve overlapping circuits.

Similar content being viewed by others

References

  1. O’Brien, C. P. & McLellan, A. T. Myths about the treatment of addiction. Lancet 347, 237–240 (1996).

    Article  PubMed  Google Scholar 

  2. Brecht, M. L. & Herbeck, D. Time to relapse following treatment for methamphetamine use: a long-term perspective on patterns and predictors. Drug. Alcohol Depend. 139, 18–25 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  3. McLellan, A. T., Lewis, D. C., O’Brien, C. P. & Kleber, H. D. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. J. Am. Med. Assoc. 284, 1689–1695 (2000).

    Article  CAS  Google Scholar 

  4. Burman, S. The challenge of sobriety: natural recovery without treatment and self-help groups. J. Subst. Abus. 9, 41–61 (1997).

    Article  CAS  Google Scholar 

  5. Kelly, J. F., Greene, M. C., Bergman, B. G., White, W. L. & Hoeppner, B. B. How many recovery attempts does it take to successfully resolve an alcohol or drug problem? Estimates and correlates from a National Study of Recovering U.S. adults. Alcohol. Clin. Exp. Res. 43, 1533–1544 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  6. SAMHSA’s working definition of recovery. SAMHSA https://store.samhsa.gov/sites/default/files/pep12-recdef.pdf (2012).

  7. About Recovery. NIDA https://nida.nih.gov/research-topics/recovery#:~:Text=Recovery%20is%20a%20process%20of,This%20is%20called%20remission (2019).

  8. International Classification of Diseases 11th Revision (ICD-11). World Health Organization https://www.who.int/standards/classifications/classification-of-diseases (2021).

  9. Robins, L. N. & Regier, D. A. (eds) Psychiatric Disorders In America: The Epidemiologic Catchment Area Study (Maxwell Macmillan International, 1991).

  10. Heyman, G. M. Quitting drugs: quantitative and qualitative features. Annu. Rev. Clin. Psychol. 9, 29–59 (2013).

    Article  PubMed  Google Scholar 

  11. Kessler, R. C. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 593–602 (2005).

    Article  PubMed  Google Scholar 

  12. Kessler, R. C. et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. results from the National Comorbidity Survey. Arch. Gen. Psychiatry 51, 8–19 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Stinson, F. S. et al. Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug. Alcohol Depend. 80, 105–116 (2005).

    Article  PubMed  Google Scholar 

  14. Jones, C. M., Noonan, R. K. & Compton, W. M. Prevalence and correlates of ever having a substance use problem and substance use recovery status among adults in the United States, 2018. Drug. Alcohol Depend. 214, 108169 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fan, A. Z., Chou, S. P., Zhang, H., Jung, J. & Grant, B. F. Prevalence and correlates of past-year recovery from DSM-5 alcohol use disorder: results from National Epidemiologic Survey On Alcohol And Related Conditions III. Alcohol. Clin. Exp. Res. 43, 2406–2420 (2019).

    Article  PubMed  Google Scholar 

  16. Key substance use and mental health indicators in the United States: results from the 2021 National Survey on Drug Use and Health. SAMHSA 64–72 https://www.samhsa.gov/data/sites/default/files/reports/rpt39443/2021NSDUHFFRRev010323.pdf (2022).

  17. Lopez-Quintero, C. et al. Probability and predictors of remission from life-time nicotine, alcohol, cannabis or cocaine dependence: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Addiction 106, 657–669 (2011).

    Article  PubMed  Google Scholar 

  18. Day, E., Manitsa, I., Farley, A. & Kelly, J. F. The UK National Recovery Survey: nationally representative survey of people overcoming a drug or alcohol problem. BJPsych Open 10, e67 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pongsavee, K., Payakkakom, A., Phukao, D. & Guadamuz, T. E. Natural recovery from alcohol: a systematic review of the literature 2006–2019. J. Subst. Use 28, 166–171 (2023).

    Article  Google Scholar 

  20. Moos, R. H. & Finney, J. W. Commentary on Lopez-Quintero et al. (2011): remission and relapse — the yin–yang of addictive disorders. Addiction 106, 670–671 (2011).

    Article  PubMed  Google Scholar 

  21. Witkiewitz, K., Pfund, R. A. & Tucker, J. A. Mechanisms of behavior change in substance use disorder with and without formal treatment. Annu. Rev. Clin. Psychol. 18, 497–525 (2022).

    Article  PubMed  Google Scholar 

  22. Klingemann, H., Sobell, M. B. & Sobell, L. C. Continuities and changes in self-change research. Addiction 105, 1510–1518 (2010).

    Article  PubMed  Google Scholar 

  23. Winick, C. S. Maturing out of narcotic addiction. Bull. Narc. 14, 1–7 (1962).

    Google Scholar 

  24. Stall, R. & Biernacki, P. Spontaneous remission from the problematic use of substances: an inductive model derived from a comparative analysis of the alcohol, opiate, tobacco, and food/obesity literatures. Int. J. Addict. 21, 1–23 (1986).

    Article  CAS  PubMed  Google Scholar 

  25. Sobell, L. C., Sobell, M. B., Toneatto, T. & Leo, G. I. What triggers the resolution of alcohol problems without treatment. Alcohol. Clin. Exp. Res. 17, 217–224, (1993).

    Article  CAS  PubMed  Google Scholar 

  26. Waldorf, D. Natural recovery from addiction: some social-psychological processes of untreated recovery. J. Drug. Issues 13, 237–280 (1983).

    Article  Google Scholar 

  27. Heilig, M. et al. Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology 46, 1715–1723 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lamb, R. J., Stark, H. G. & Ginsburg, B. C. Implications of there being many paths to addiction and recovery. Pharmacol. Biochem. Behav. 211, 173299 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Godino, A. et al. Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards. Neuron 111, 1453–1467 e1457 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kennedy, P. J. et al. Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation. Nat. Neurosci. 16, 434–440 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, Y. et al. Synaptic mechanism underlying serotonin modulation of transition to cocaine addiction. Science 373, 1252–1256 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pascoli, V. et al. Stochastic synaptic plasticity underlying compulsion in a model of addiction. Nature 564, 366–371 (2018).

    Article  CAS  PubMed  Google Scholar 

  33. Nestler, E. J. & Luscher, C. The molecular basis of drug addiction: linking epigenetic to synaptic and circuit mechanisms. Neuron 102, 48–59 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bordeaux, P. & Koob, G. F. Escaping Addiction: Resetting the Brain for Success (Rowman & Littlefield, 2023).

  35. Balodis, I. M. et al. Neurofunctional reward processing changes in cocaine dependence during recovery. Neuropsychopharmacology 41, 2112–2121 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yip, S. W., Scheinost, D., Potenza, M. N. & Carroll, K. M. Connectome-based prediction of cocaine abstinence. Am. J. Psychiatry 176, 156–164 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Parvaz, M. A., Rabin, R. A., Adams, F. & Goldstein, R. Z. Structural and functional brain recovery in individuals with substance use disorders during abstinence: a review of longitudinal neuroimaging studies. Drug. Alcohol Depend. 232, 109319 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Goldstein, R. Z. & Volkow, N. D. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat. Rev. Neurosci. 12, 652–669, (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Maggioni, E. et al. Brain volumes in alcohol use disorder: do females and males differ? A whole-brain magnetic resonance imaging mega-analysis. Hum. Brain Mapp. 44, 4652–4666 (2023).

  40. Spindler, C., Mallien, L., Trautmann, S., Alexander, N. & Muehlhan, M. A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder. Transl. Psychiatry 12, 40 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yang, X. et al. Cortical and subcortical gray matter shrinkage in alcohol-use disorders: a voxel-based meta-analysis. Neurosci. Biobehav. Rev. 66, 92–103 (2016).

    Article  CAS  PubMed  Google Scholar 

  42. Garavan, H., Brennan, K. L., Hester, R. & Whelan, R. The neurobiology of successful abstinence. Curr. Opin. Neurobiol. 23, 668–674 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hammond, C. J., Allick, A., Rahman, N. & Nanavati, J. Structural and functional neural targets of addiction treatment in adolescents and young adults: a systematic review and meta-analysis. J. Child. Adolesc. Psychopharmacol. 29, 498–507 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Costumero, V. et al. Distance disintegration characterizes node-level topological dysfunctions in cocaine addiction. Addict. Biol. 26, e13072 (2021).

    Article  PubMed  Google Scholar 

  45. Zilverstand, A. et al. Whole-brain resting-state connectivity underlying impaired inhibitory control during early versus longer-term abstinence in cocaine addiction. Mol. Psychiatry 28, 3355–3364 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Huang, Y. et al. Association of cortico-striatal engagement during cue reactivity, reappraisal, and savoring of drug and non-drug stimuli with craving in heroin addiction. Am. J. Psychiatry 181, 153–165 (2024).

    Article  PubMed  Google Scholar 

  47. Joutsa, J. et al. Brain lesions disrupting addiction map to a common human brain circuit. Nat. Med. 28, 1249–1255 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Fox, M. D. Mapping symptoms to brain networks with the human connectome. N. Engl. J. Med. 379, 2237–2245 (2018).

    Article  CAS  PubMed  Google Scholar 

  49. Venniro, M., Banks, M. L., Heilig, M., Epstein, D. H. & Shaham, Y. Improving translation of animal models of addiction and relapse by reverse translation. Nat. Rev. Neurosci. 21, 625–643 (2020).

    Article  CAS  PubMed  Google Scholar 

  50. Humphreys, K. & Bickel, W. K. Toward a neuroscience of long-term recovery from addiction. JAMA Psychiatry 75, 875–876 (2018).

    Article  PubMed  Google Scholar 

  51. Ceceli, A. O., Bradberry, C. W. & Goldstein, R. Z. The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex. Neuropsychopharmacology 47, 276–291 (2022).

    Article  PubMed  Google Scholar 

  52. Bischof, G., Rumpf, H. J., Hapke, U., Meyer, C. & John, U. Factors influencing remission from alcohol dependence without formal help in a representative population sample. Addiction 96, 1327–1336 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Scherbaum, N. & Specka, M. Factors influencing the course of opiate addiction. Int. J. Meth. Psychiatric Res. 17, S39–S44 (2008).

    Article  Google Scholar 

  54. Granfield, R. & Cloud, W. Social context and “natural recovery”: the role of social capital in the resolution of drug-associated problems. Subst. Use Misuse 36, 1543–1570 (2001).

    Article  CAS  PubMed  Google Scholar 

  55. Acuff, S. F., MacKillop, J. & Murphy, J. G. A contextualized reinforcer pathology approach to addiction. Nat. Rev. Psychol. 2, 309–323 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Pickard, H. & Ahmed, S. H. in Addiction and Choice: Rethinking the Relationship 29–48 (Oxford Univ. Press, 2017).

  57. Engeln, M. & Ahmed, S. H. The multiple faces of footshock punishment in animal research on addiction. Neurobiol. Learn. Mem. 213, 107955 (2024).

    Article  PubMed  Google Scholar 

  58. Kim, C. K. et al. Molecular and circuit-dynamical identification of top-down neural mechanisms for restraint of reward seeking. Cell 170, 1013–1027.e1014 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Park, J. & Moghaddam, B. Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons. eLife 6, e30056 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bellone, C., Loureiro, M. & Luscher, C. Drug-evoked synaptic plasticity of excitatory transmission in the ventral tegmental area. Cold Spring Harb. Perspect. Med. 11, a039701 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lammel, S., Ion, D. I., Roeper, J. & Malenka, R. C. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 70, 855–862 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. de Jong, J. W. et al. A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. Neuron 101, 133–151.e137 (2019).

    Article  PubMed  Google Scholar 

  63. Zhou, K. et al. Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice. Nat. Commun. 13, 6244 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Vollmer, K. M. et al. An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice. Nat. Commun. 13, 6865 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Choi, E. A., Jean-Richard-Dit-Bressel, P., Clifford, C. W. G. & McNally, G. P. Paraventricular thalamus controls behavior during motivational conflict. J. Neurosci. 39, 4945–4958 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Choi, E. A. & McNally, G. P. Paraventricular thalamus balances danger and reward. J. Neurosci. 37, 3018–3029 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. King, S. G. et al. Prefrontal-habenular microstructural impairments in human cocaine and heroin addiction. Neuron 110, 3820–3832.e3824 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mathis, V. & Kenny, P. J. From controlled to compulsive drug-taking: the role of the habenula in addiction. Neurosci. Biobehav. Rev. 106, 102–111 (2019).

    Article  PubMed  Google Scholar 

  69. Meye, F. J. et al. Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse. Nat. Neurosci. 19, 1019–1024 (2016).

    Article  CAS  PubMed  Google Scholar 

  70. Ables, J. L., Park, K. & Ibanez-Tallon, I. Understanding the habenula: a major node in circuits regulating emotion and motivation. Pharmacol. Res. 190, 106734 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Goldstein, R. Z. et al. Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction. Proc. Natl Acad. Sci. USA 106, 9453–9458 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Goldstein, R. Z. et al. Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? Am. J. Psychiatry 164, 43–51 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Jean-Richard-Dit-Bressel, P., Killcross, S. & McNally, G. P. Behavioral and neurobiological mechanisms of punishment: implications for psychiatric disorders. Neuropsychopharmacology 43, 1639–1650 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ma, C. et al. Medial orbitofrontal cortex regulates instrumental conditioned punishment, but not pavlovian conditioned fear. Cereb. Cortex Commun. 1, tgaa039 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Orsini, C. A., Trotta, R. T., Bizon, J. L. & Setlow, B. Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment. J. Neurosci. 35, 1368–1379 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Cadet, J. L., Patel, R. & Jayanthi, S. Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: epigenetic and transcriptional consequences in the rat brain. Pharmacol. Biochem. Behav. 179, 98–108 (2019).

    Article  CAS  PubMed  Google Scholar 

  77. Torres, O. V., Jayanthi, S., McCoy, M. T. & Cadet, J. L. Selective activation of striatal NGF-TrkA/p75NTR/MAPK intracellular signaling in rats that show suppression of methamphetamine intake 30 days following drug abstinence. Int. J. Neuropsychopharmacol. 21, 281–290 (2018).

    Article  CAS  PubMed  Google Scholar 

  78. Swanson, A. M., DePoy, L. M. & Gourley, S. L. Inhibiting Rho kinase promotes goal-directed decision making and blocks habitual responding for cocaine. Nat. Commun. 8, 1861 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Blackwood, C. A., McCoy, M. T., Ladenheim, B. & Cadet, J. L. Escalated oxycodone self-administration and punishment: differential expression of opioid receptors and immediate early genes in the rat dorsal striatum and prefrontal cortex. Front. Neurosci. 13, 1392 (2019).

    Article  PubMed  Google Scholar 

  80. McClung, C. A. et al. DeltaFosB: a molecular switch for long-term adaptation in the brain. Brain Res. Mol. Brain Res. 132, 146–154 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Nestler, E. J. FosB: a transcriptional regulator of stress and antidepressant responses. Eur. J. Pharmacol. 753, 66–72 (2015).

    Article  CAS  PubMed  Google Scholar 

  82. Renthal, W. et al. Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins. Neuron 62, 335–348 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pitchers, K. K. et al. Natural and drug rewards act on common neural plasticity mechanisms with DeltaFosB as a key mediator. J. Neurosci. 33, 3434–3442 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Cadet, J. L. et al. Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence. Mol. Psychiatry 22, 1196–1204 (2017).

    Article  CAS  PubMed  Google Scholar 

  85. Pascoli, V. et al. Cell-type specific synaptic plasticity in dorsal striatum is associated with punishment-resistance compulsive-like cocaine self-administration in mice. Neuropsychopharmacology 48, 448–458 (2023).

    Article  CAS  PubMed  Google Scholar 

  86. Krasnova, I. N. et al. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence. Neuropsychopharmacology 39, 2008–2016 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Negishi, K., Fredriksson, I., Bossert, J. M., Zangen, A. & Shaham, Y. Relapse after electric barrier-induced voluntary abstinence: a review. Curr. Opin. Neurobiol. 86, 102856 (2024).

    Article  CAS  PubMed  Google Scholar 

  88. Hill, K., Bodurtha, P. J., Winkelman, T. N. A. & Howell, B. A. Postrelease risk of overdose and all-cause death among persons released from jail or prison: minnesota, March 2020–December 2021. Am. J. Public. Health 114, 913–922 (2024).

    Article  PubMed  Google Scholar 

  89. Joudrey, P. J. et al. A conceptual model for understanding post-release opioid-related overdose risk. Addict. Sci. Clin. Pract. 14, 17 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Strang, J. Death matters: understanding heroin/opiate overdose risk and testing potential to prevent deaths. Addiction 110, 27–35 (2015).

    Article  PubMed  Google Scholar 

  91. DuPont, R. L., McLellan, A. T., White, W. L., Merlo, L. J. & Gold, M. S. Setting the standard for recovery: physicians’ health programs. J. Subst. Abus. Treat. 36, 159–171 (2009).

    Article  Google Scholar 

  92. Fuller, R. K. et al. Disulfiram treatment of alcoholism. A Veterans Administration cooperative study. JAMA 256, 1449–1455 (1986).

    Article  CAS  PubMed  Google Scholar 

  93. Chen, B. T. et al. Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature 496, 359–362 (2013).

    Article  CAS  PubMed  Google Scholar 

  94. Pascoli, V., Terrier, J., Hiver, A. & Luscher, C. Sufficiency of mesolimbic dopamine neuron stimulation for the progression to addiction. Neuron 88, 1054–1066 (2015).

    Article  CAS  PubMed  Google Scholar 

  95. Durand, A., Girardeau, P., Freese, L. & Ahmed, S. H. Increased responsiveness to punishment of cocaine self-administration after experience with high punishment. Neuropsychopharmacology 47, 444–453 (2022).

    Article  CAS  PubMed  Google Scholar 

  96. Domi, E. et al. Activation of GABA(B) receptors in central amygdala attenuates activity of PKCdelta + neurons and suppresses punishment-resistant alcohol self-administration in rats. Neuropsychopharmacology 48, 1386–1395 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Giuliano, C., Belin, D. & Everitt, B. J. Compulsive alcohol seeking results from a failure to disengage dorsolateral striatal control over behavior. J. Neurosci. 39, 1744–1754 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Lee, S. M. et al. Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system and cocaine seeking-behaviors. J. Neurosci. 42, 9180–9192 (2022).

  99. McNally, G. P., Jean-Richard-Dit-Bressel, P., Millan, E. Z. & Lawrence, A. J. Pathways to the persistence of drug use despite its adverse consequences. Mol. Psychiatry 28, 2228–2237 (2023).

  100. Pickard, H. & Ahmed, S. H. The Routledge Handbook of Philosophy and Science of Addiction (Routledge, 2018).

  101. Jean-Richard-Dit-Bressel, P., Ma, C., Bradfield, L. A., Killcross, S. & McNally, G. P. Punishment insensitivity emerges from impaired contingency detection, not aversion insensitivity or reward dominance. eLife 8, e52765 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Marchant, N. J., Khuc, T. N., Pickens, C. L., Bonci, A. & Shaham, Y. Context-induced relapse to alcohol seeking after punishment in a rat model. Biol. Psychiatry 73, 256–262 (2013).

    Article  CAS  PubMed  Google Scholar 

  103. Ghareh, H. et al. Role of anterior insula cortex in context-induced relapse of nicotine-seeking. eLife 11, e75609 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Sinha, R. Modeling relapse situations in the human laboratory. Curr. Top. Behav. Neurosci. 13, 379–402 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  105. McDonald, A. J. et al. Alcohol seeking under risk of punishment is associated with activation of cortical and subcortical brain regions. Front. Behav. Neurosci. 15, 739681 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Choi, E. A. et al. A corticothalamic circuit trades off speed for safety during decision-making under motivational conflict. J. Neurosci. 42, 3473–3483 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wang, T. et al. Paraventricular thalamus dynamically modulates aversive memory via tuning prefrontal inhibitory circuitry. J. Neurosci. 43, 3630–3646 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. McNally, G. P. Motivational competition and the paraventricular thalamus. Neurosci. Biobehav. Rev. 125, 193–207 (2021).

    Article  PubMed  Google Scholar 

  109. Hennigan, K., D’Ardenne, K. & McClure, S. M. Distinct midbrain and habenula pathways are involved in processing aversive events in humans. J. Neurosci. 35, 198–208 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hsu, D. T., Kirouac, G. J., Zubieta, J. K. & Bhatnagar, S. Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood. Front. Behav. Neurosci. 8, 73 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Jensen, J. et al. Direct activation of the ventral striatum in anticipation of aversive stimuli. Neuron 40, 1251–1257 (2003).

    Article  CAS  PubMed  Google Scholar 

  112. Ahmed, S. H. Imbalance between drug and non-drug reward availability: a major risk factor for addiction. Eur. J. Pharmacol. 526, 9–20 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Venniro, M. et al. The protective effect of social reward on opioid and psychostimulant reward and relapse: behavior, pharmacology, and brain regions. J. Neurosci. 42, 9298–9314 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Venniro, M., Panlilio, L. V., Epstein, D. H. & Shaham, Y. The protective effect of operant social reward on cocaine self-administration, choice, and relapse is dependent on delay and effort for the social reward. Neuropsychopharmacology 46, 2350–2357 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Venniro, M. et al. Volitional social interaction prevents drug addiction in rat models. Nat. Neurosci. 21, 1520–1529 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Grimm, J. W., Hope, B. T., Wise, R. A. & Shaham, Y. Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412, 141–142, (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. de Boer, S. F., Buwalda, B. & Koolhaas, J. M. Untangling the neurobiology of coping styles in rodents: towards neural mechanisms underlying individual differences in disease susceptibility. Neurosci. Biobehav. Rev. 74, 401–422 (2017).

    Article  PubMed  Google Scholar 

  118. Krach, S., Paulus, F. M., Bodden, M. & Kircher, T. The rewarding nature of social interactions. Front. Behav. Neurosci. 4, 22 (2010).

    PubMed  PubMed Central  Google Scholar 

  119. Schweinfurth, M. K. The social life of Norway rats (Rattus norvegicus). eLife 9, e54020 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  120. El Rawas, R. et al. Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction. Front. Behav. Neurosci. 6, 63 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Leong, K. C., Cox, S., King, C., Becker, H. & Reichel, C. M. Oxytocin and rodent models of addiction. Int. Rev. Neurobiol. 140, 201–247 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tomova, L. et al. Acute social isolation evokes midbrain craving responses similar to hunger. Nat. Neurosci. 23, 1597–1605 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Gunaydin, L. A. et al. Natural neural projection dynamics underlying social behavior. Cell 157, 1535–1551 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hung, L. W. et al. Gating of social reward by oxytocin in the ventral tegmental area. Science 357, 1406–1411 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Dolen, G., Darvishzadeh, A., Huang, K. W. & Malenka, R. C. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179–184 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Ibragimov, R., Kovacs, G. L., Szabo, G. & Telegdy, G. Microinjection of oxytocin into limbic-mesolimbic brain structures disrupts heroin self-administration behavior: a receptor-mediated event? Life Sci. 41, 1265–1271 (1987).

    Article  CAS  PubMed  Google Scholar 

  127. Weber, R. A. et al. Regionally specific effects of oxytocin on reinstatement of cocaine seeking in male and female rats. Int. J. Neuropsychopharmacol. 21, 677–686 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Venniro, M. et al. Abstinence-dependent dissociable central amygdala microcircuits control drug craving. Proc. Natl Acad. Sci. USA 117, 8126–8134 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Domi, E. et al. A neural substrate of compulsive alcohol use. Sci. Adv. 7, eabg9045 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Marchant, N. J. et al. Rats choose alcohol over social reward in an operant choice procedure. Neuropsychopharmacology 48, 585–593 (2023).

  131. Augier, G. et al. Wistar rats choose alcohol over social interaction in a discrete-choice model. Neuropsychopharmacology 49, 1098–1107 (2022).

    Google Scholar 

  132. Chow, J. J. et al. Characterization of operant social interaction in rats: effects of access duration, effort, peer familiarity, housing conditions, and choice between social interaction vs. food or remifentanil. Psychopharmacology 239, 2093–2108 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Alexander, B. K., Beyerstein, B. L., Hadaway, P. F. & Coambs, R. B. Effect of early and later colony housing on oral ingestion of morphine in rats. Pharmacol. Biochem. Behav. 15, 571–576 (1981).

    Article  CAS  PubMed  Google Scholar 

  134. Smith, M. A. Peer influences on drug self-administration: social facilitation and social inhibition of cocaine intake in male rats. Psychopharmacology 224, 81–90 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Papamihali, K. et al. Convenience and comfort: reasons reported for using drugs alone among clients of harm reduction sites in British Columbia, Canada. Harm Reduct. J. 17, 90 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Roe, L. et al. Isolation, solitude and social distancing for people who use drugs: an ethnographic perspective. Front. Psychiatry 11, 623032 (2020).

    Article  PubMed  Google Scholar 

  137. Strickland, J. C. & Acuff, S. F. Role of social context in addiction etiology and recovery. Pharmacol. Biochem. Behav. 229, 173603 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Pelloux, Y., Giorla, E., Montanari, C. & Baunez, C. Social modulation of drug use and drug addiction. Neuropharmacology 159, 107545 (2019).

    Article  CAS  PubMed  Google Scholar 

  139. Mayock, P. & Butler, S. “I’m always hiding and ducking and diving”: the stigma of growing older on methadone. Drugs Educ. Prev. Policy 29, 139–149 (2022).

    Article  Google Scholar 

  140. Engeln, M., Fox, M. E. & Lobo, M. K. Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat stress. Psychopharmacology 238, 41–54 (2021).

    Article  CAS  PubMed  Google Scholar 

  141. Heilig, M., Epstein, D. H., Nader, M. A. & Shaham, Y. Time to connect: bringing social context into addiction neuroscience. Nat. Rev. Neurosci. 17, 592–599 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Scheggia, D. et al. Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice. Nat. Neurosci. 25, 1505–1518 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rabin, R. A., Parvaz, M. A., Alia-Klein, N. & Goldstein, R. Z. Emotion recognition in individuals with cocaine use disorder: the role of abstinence length and the social brain network. Psychopharmacology 239, 1019–1033 (2022).

    Article  CAS  PubMed  Google Scholar 

  144. Chang, V. N. & Peters, J. Neural circuits controlling choice behavior in opioid addiction. Neuropharmacology 226, 109407 (2023).

    Article  CAS  PubMed  Google Scholar 

  145. Lenoir, M. et al. Large-scale brain correlates of sweet versus cocaine reward in rats. Eur. J. Neurosci. 57, 423–439 (2023).

    Article  CAS  PubMed  Google Scholar 

  146. Haubrich, J. & Nader, K. in Behavioral Neuroscience of Learning and Memory (eds Clark, R. E. & Martin, S. J.) 151–176 (Springer International Publishing, 2018).

  147. Bernabo, M., Haubrich, J., Gamache, K. & Nader, K. Memory destabilization and reconsolidation dynamically regulate the PKMζ maintenance mechanism. J. Neurosci. 41, 4880–4888 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Huang, Y. H. et al. In vivo cocaine experience generates silent synapses. Neuron 63, 40–47 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Wright, W. J. & Dong, Y. Silent synapses in cocaine-associated memory and beyond. J. Neurosci. 41, 9275–9285 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Engeln, M. et al. Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward. Mol. Psychiatry 27, 3980–3991 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Finkelstein, A. B. et al. Social reactivation of fear engrams enhances memory recall. Proc. Natl Acad. Sci. USA 119, e2114230119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Smith, K. E. Disease and decision. J. Subst. Abus. Treat. 142, 108874 (2022).

    Article  CAS  Google Scholar 

  153. Lim, D. H., Yoon, Y. J., Her, E., Huh, S. & Jung, M. W. Active maintenance of eligibility trace in rodent prefrontal cortex. Sci. Rep. 10, 18860 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Liu, X. et al. Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit. Mol. Psychiatry 29, 730–741 (2024).

    Article  PubMed  Google Scholar 

  155. Kober, H. et al. Prefrontal–striatal pathway underlies cognitive regulation of craving. Proc. Natl Acad. Sci. USA 107, 14811–14816 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Rescorla, R. A. & Wagner, A. R. A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and non-reinforcement. In Classical Conditioning: Current Research and Theory Vol. 2 (eds Black, A. H. & Prokasy, W. F.) 64–69 (Appleton-Century-Crofts, 1972).

  157. Pedreira, M. E., Perez-Cuesta, L. M. & Maldonado, H. Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction. Learn. Mem. 11, 579–585, (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Kendler, K. S. & Woodward, J. Top-down causation in psychiatric disorders: a clinical-philosophical inquiry. Psychol. Med. 51, 1783–1788 (2021).

    Article  PubMed  Google Scholar 

  159. Milton, A. L. & Everitt, B. J. The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction. Eur. J. Neurosci. 31, 2308–2319, (2010).

    Article  PubMed  Google Scholar 

  160. Pachas, G. N. et al. Single dose propranolol does not affect physiologic or emotional reactivity to smoking cues. Psychopharmacology 232, 1619–1628 (2015).

    Article  CAS  PubMed  Google Scholar 

  161. Xue, Y. X. et al. Effect of selective inhibition of reactivated nicotine-associated memories with propranolol on nicotine craving. JAMA Psychiatry 74, 224–232, (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  162. Lonergan, M. et al. Reactivating addiction-related memories under propranolol to reduce craving: a pilot randomized controlled trial. J. Behav. Ther. Exp. Psychiatry 50, 245–249 (2016).

    Article  PubMed  Google Scholar 

  163. Jobes, M. L. et al. Effects of prereactivation propranolol on cocaine craving elicited by imagery script/cue sets in opioid-dependent polydrug users: a randomized study. J. Addict. Med. 9, 491–498 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Bornstein, A. M. & Pickard, H. “Chasing the first high”: memory sampling in drug choice. Neuropsychopharmacology 45, 907–915 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Davis, R. L. & Zhong, Y. The biology of forgetting—a perspective. Neuron 95, 490–503 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Gallo, F. T. et al. Dopamine modulates adaptive forgetting in medial prefrontal cortex. J. Neurosci. 42, 6620–6636 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Kerchner, G. A. & Nicoll, R. A. Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat. Rev. Neurosci. 9, 813–825 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Rogerson, T. et al. Synaptic tagging during memory allocation. Nat. Rev. Neurosci. 15, 157–169 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Cai, D. J. et al. A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534, 115–118 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Yetton, B. D., Cai, D. J., Spoormaker, V. I., Silva, A. J. & Mednick, S. C. Human memories can be linked by temporal proximity. Front. Hum. Neurosci. 13, 315 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Koob, G. F., Sanna, P. P. & Bloom, F. E. Neuroscience of addiction. Neuron 21, 467–476 (1998).

    Article  CAS  PubMed  Google Scholar 

  172. Koob, G. F. & Volkow, N. D. Neurocircuitry of addiction. Neuropsychopharmacology 35, 217–238 (2010).

    Article  PubMed  Google Scholar 

  173. Schlag, A. K. Percentages of problem drug use and their implications for policy making: a review of the literature. Drug. Sci. Policy Law 6, 2050324520904540 (2020).

    Article  Google Scholar 

  174. Schultz, W. Updating dopamine reward signals. Curr. Opin. Neurobiol. 23, 229–238 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Piantadosi, P. T., Yeates, D. C. M., Wilkins, M. & Floresco, S. B. Contributions of basolateral amygdala and nucleus accumbens subregions to mediating motivational conflict during punished reward-seeking. Neurobiol. Learn. Mem. 140, 92–105 (2017).

    Article  PubMed  Google Scholar 

  176. Leong, K. C. et al. Oxytocin reduces cocaine cued Fos activation in a regionally specific manner. Int. J. Neuropsychopharmacol. 20, 844–854 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Lenoir, M., Engeln, M., Navailles, S., Girardeau, P. & Ahmed, S. H. A large-scale c-Fos brain mapping study on extinction of cocaine-primed reinstatement. Neuropsychopharmacology 49, 1459–1467 (2024).

    Article  CAS  PubMed  Google Scholar 

  178. Pelloux, Y., Minier-Toribio, A., Hoots, J. K., Bossert, J. M. & Shaham, Y. Opposite effects of basolateral amygdala inactivation on context-induced relapse to cocaine seeking after extinction versus punishment. J. Neurosci. 38, 51–59 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Diniz, C. & Crestani, A. P. The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity. Mol. Psychiatry 28, 977–992 (2023).

    Article  PubMed  Google Scholar 

  180. Bozon, B., Davis, S. & Laroche, S. A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40, 695–701 (2003).

    Article  CAS  PubMed  Google Scholar 

  181. Chandra, R. et al. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine-mediated regulation of Tiam1. Front. Mol. Neurosci. 6, 13 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Tu, G. et al. Dopamine D1 and D2 receptors differentially regulate Rac1 and Cdc42 signaling in the nucleus accumbens to modulate behavioral and structural plasticity after repeated methamphetamine treatment. Biol. Psychiatry 86, 820–835 (2019).

    Article  CAS  PubMed  Google Scholar 

  183. Roesler, R. Molecular mechanisms controlling protein synthesis in memory reconsolidation. Neurobiol. Learn. Mem. 142, 30–40 (2017).

    Article  CAS  PubMed  Google Scholar 

  184. Barak, S. & Goltseker, K. Targeting the reconsolidation of licit drug memories to prevent relapse: focus on alcohol and nicotine. Int. J. Mol. Sci. 22, 4090 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Chamberlain, S. R., Muller, U., Blackwell, A. D., Robbins, T. W. & Sahakian, B. J. Noradrenergic modulation of working memory and emotional memory in humans. Psychopharmacology 188, 397–407 (2006).

    Article  CAS  PubMed  Google Scholar 

  186. Otis, J. M. & Mueller, D. Reversal of cocaine-associated synaptic plasticity in medial prefrontal cortex parallels elimination of memory retrieval. Neuropsychopharmacology 42, 2000–2010 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Akirav, I. & Maroun, M. Stress modulation of reconsolidation. Psychopharmacology 226, 747–761, (2013).

    Article  CAS  PubMed  Google Scholar 

  188. Haubrich, J., Bernabo, M. & Nader, K. Noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory reconsolidation. eLife 9, e57010 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Sanchez Beisel, J. M., Maza, F. J., Justel, N., Fernandez Larrosa, P. N. & Delorenzi, A. Embodiment of an emotional state concurs with a stress-induced reconsolidation impairment effect on an auditory verbal word-list memory. Neuroscience 497, 239–256 (2022).

    Article  CAS  PubMed  Google Scholar 

  190. Goltseker, K., Handrus, H. & Barak, S. Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval. Addict. Biol. 26, e12935 (2021).

    Article  PubMed  Google Scholar 

  191. Goltseker, K., Bolotin, L. & Barak, S. Counterconditioning during reconsolidation prevents relapse of cocaine memories. Neuropsychopharmacology 42, 716–726 (2017).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the French Research Council (CNRS), the Université de Bordeaux, the French National Agency (ANR-22-CE37-0004 to M.E. and ANR-19-CE37-0013 to S.H.A.) and IReSP/INCa (SPAV1-22-003 to S.H.A.).

Author information

Authors and Affiliations

  1. Univ. Bordeaux, CNRS, INCIA, UMR 5287, Bordeaux, France

    Michel Engeln & Serge H. Ahmed

Authors
  1. Michel Engeln
    View author publications

    Search author on:PubMed Google Scholar

  2. Serge H. Ahmed
    View author publications

    Search author on:PubMed Google Scholar

Contributions

M.E. researched data for the article. Both authors contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Michel Engeln.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Peer review

Peer review information

Nature Reviews Neuroscience thanks Yan Dong, Yavin Shaham, Yingjie Zhu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Engeln, M., Ahmed, S.H. Remission from addiction: erasing the wrong circuits or making new ones?. Nat. Rev. Neurosci. 26, 115–130 (2025). https://doi.org/10.1038/s41583-024-00886-y

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41583-024-00886-y

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing