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Cravings & Relapse

Why cravings can return after months, how cues work, and why relapse risk can persist during recovery. This page highlights research articles from the AddictionTube science database and links each summary to the original source.

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These article summaries are meant to help visitors understand the research language around cravings & relapse. Use them as background education, then open the original article source for more detail.

Featured article summaries

Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking

This article may help explain addiction science through research on cocaine, brain science, craving, relapse. The source abstract begins by describing: “Cocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment.”

Key finding: These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.

Neuropsychopharmacology • 02 Aug 2023 • Research

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Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats

This article may help explain addiction science through research on opioid, alcohol, nicotine, brain science. The source abstract begins by describing: “Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking.”

Key finding: We conclude that psilocybin reduces heroin relapse and highlight IL-17a signaling as a potential downstream pathway of psilocybin that also reduces heroin seeking.

Molecular Psychiatry • 21 Oct 2024 • Research

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A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking

This article may help explain addiction science through research on opioid, cocaine, brain science, craving. The source abstract begins by describing: “We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans.”

Key finding: The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

Nature Communications • 14 Jul 2015 • Research

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Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving

This article may help explain addiction science through research on cocaine, dopamine, craving, relapse. The source abstract begins by describing: “Relapse represents a consistent clinical problem for individuals with substance use disorder.”

Key finding: These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.

Neuropsychopharmacology • 19 Sept 2024 • Research

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Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats

This article may help explain addiction science through research on cocaine, brain science, craving, relapse. The source abstract begins by describing: “Persistent susceptibility to cue-induced relapse is a cardinal feature of addiction.”

Key finding: Finally, using ex vivo whole-cell recordings from pyramidal neurons in the medial prefrontal cortex, we demonstrate that the disruption of DS-controlled cocaine seeking following infralimbic cortex microinjections of muscimol+baclofen is likely a result of suppression of synaptic transmission in the region via a presynaptic mechanism of action.

Neuropsychopharmacology • 23 Jun 2021 • Research

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AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking

This article may help explain addiction science through research on cocaine, brain science, craving, relapse. The source abstract begins by describing: “Relapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence.”

Key finding: Altogether, these results indicate that AMPK activity in the NAc core is critical for the cue-induced reinstatement of cocaine seeking, which may be mediated by mTORC1 and ERK1/2 signaling.

Scientific Reports • 21 Apr 2017 • Research

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Found in translation: orexin receptor antagonism for the treatment of opioid use disorder

This article may help explain addiction science through research on opioid, withdrawal, craving, relapse. The source abstract begins by describing: “Existing pharmacological treatment options for opioid use disorder (OUD) face challenges that limit their efficacy.”

Key finding: This review adopts a translational approach to achieve several aims: (1) to outline the fundamental theories of orexin system function and relate orexinergic dysfunction to the disordered motivation and withdrawal states that characterize OUD; (2) to provide an up-to-date evaluation of preclinical and clinical evidence bases supporting the efficacy of orexin receptor antagonism for the treatment of OUD; (3) to discuss key clinical considerations of repurposing DORAs for OUD treatment, including safety and side effects (i.e., respiratory depression, anhedonia, and risk for abuse); and (4) to highlight the ongoing clinical efforts to determine therapeutic efficacy and safety profiles of DORAs for use in OUD populations.

Translational Psychiatry • 24 Oct 2025 • Reviews

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Synaptic mechanisms underlying persistent cocaine craving

This article may help explain addiction science through research on cocaine, brain science, craving, relapse. The source abstract begins by describing: “One of the greatest challenges in treating addiction is preventing relapse during abstinence.”

Key finding: Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction.

Nature Reviews Neuroscience • 06 May 2016 • Reviews

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Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking

This article may help explain addiction science through research on cocaine, dopamine, brain science, craving. The source abstract begins by describing: “The authors show that rostral ventral pallidum projections to the ventral tegmental area (VTA) are activated during cue-induced reinstatement of cocaine seeking, and DREADD inhibition of these projections blocks this behavior.”

Key finding: This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction.

Nature Neuroscience • 02 Mar 2014 • Research

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Conditioned Contribution of Peripheral Cocaine Actions to Cocaine Reward and Cocaine-Seeking

This article may help explain addiction science through research on cocaine, dopamine, brain science, craving. The source abstract begins by describing: “Cocaine has actions in the peripheral nervous system that reliably precede—and thus predict—its soon-to-follow central rewarding effects.”

Key finding: These findings suggest that the conditioned peripheral effects of cocaine can contribute significantly to cocaine-induced (but not stress-induced) cocaine craving, and also suggest the cocaine cue as an important target for cue-exposure therapies for cocaine addiction.

Neuropsychopharmacology • 27 Mar 2013 • Research

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The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile

This article may help explain addiction science through research on alcohol, craving, relapse, mental health. The source abstract begins by describing: “Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side…”

Key finding: Taken together, these results demonstrate the involvement of calpains in alcohol-seeking and relapse and present a rationale for a novel pharmacological intervention that may reduce craving and relapse with minimal side effects in alcohol-dependent patients.

Neuropsychopharmacology • 28 Jul 2015 • Research

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Exploring regulation and function of dopamine D3 receptors in alcohol use disorder. A PET [11C]-(+)-PHNO study

This article may help explain addiction science through research on alcohol, dopamine, craving, relapse. The source abstract begins by describing: “Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD).”

Key finding: Furthermore, the finding that binding in the SN is associated with alcohol demand warrants further examination.

Neuropsychopharmacology • 04 Aug 2021 • Research

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Effect of the dopamine stabilizer (-)-OSU6162 on potentiated incubation of opioid craving after electric barrier-induced voluntary abstinence

This article may help explain addiction science through research on opioid, dopamine, craving, relapse. The source abstract begins by describing: “In the classical incubation of drug craving rat model, drug seeking is assessed after homecage forced abstinence.”

Key finding: We propose the dopamine stabilizer (−)-OSU6162 may serve as an adjunct pharmacological treatment to prevent relapse in male opioid users.

Neuropsychopharmacology • 06 Jan 2020 • Research

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The effect of chronic oxytocin treatment during abstinence from methamphetamine self-administration on incubation of craving, reinstatement, and anxiety

This article may help explain addiction science through research on methamphetamine, craving, relapse, mental health. The source abstract begins by describing: “Methamphetamine (METH) abuse is characterised by chronic relapse and anxiety, for which there are no effective pharmacotherapies.”

Key finding: Using a translatable addiction model, these findings demonstrate the therapeutic efficacy of chronic oxytocin after METH self-administration and supports the clinical utility of oxytocin for METH addiction in both sexes.

Neuropsychopharmacology • 12 Nov 2019 • Research

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Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence

This article may help explain addiction science through research on alcohol, nicotine, brain science, craving. The source abstract begins by describing: “Chronic alcohol use has important effects on the glutamate system.”

Key finding: These findings provide human evidence consistent with a robust preclinical literature supporting mGlu5 receptor drugs as pharmacotherapies for AUD.

Neuropsychopharmacology • 12 Sept 2020 • Research

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Silent synapses dictate cocaine memory destabilization and reconsolidation

This article may help explain addiction science through research on cocaine, withdrawal, craving, relapse. The source abstract begins by describing: “Cocaine-associated memories are persistent, but, on retrieval, become temporarily destabilized and vulnerable to disruptions, followed by reconsolidation.”

Key finding: Cocaine-generated silent synapses dictate the encoding, consolidation, retrieval-induced destabilization and reconsolidation of cocaine memories, and these syapses can be targeted to reduce drug seeking and relapse.

Nature Neuroscience • 02 Dec 2019 • Research

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Nicotine dependence and insula subregions: functional connectivity and cue-induced activation

This article may help explain addiction science through research on nicotine, brain science, craving, relapse. The source abstract begins by describing: “Nicotine dependence is a major predictor of relapse in people with Tobacco Use Disorder (TUD).”

Key finding: These results may inform therapeutic approaches, such as brain stimulation, which may elicit differential clinical outcomes (e.g., dependence, craving) depending on the insular subnetwork that is targeted.

Neuropsychopharmacology • 03 Mar 2023 • Research

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A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse

This article may help explain addiction science through research on cocaine, craving, relapse, treatment. The source abstract begins by describing: “Cocaine addiction is characterized by high relapse rates associated with glutamate dysregulation, presenting significant challenges for long-term treatment.”

Key finding: A single NAC treatment combined with extinction training can produce lasting suppression of relapse, highlighting its therapeutic promise for addiction treatment.

Translational Psychiatry • 19 Mar 2026 • Research

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Inhibition of actin polymerization in the NAc shell inhibits morphine-induced CPP by disrupting its reconsolidation

This article may help explain addiction science through research on opioid, brain science, craving, relapse. The source abstract begins by describing: “Drug-associated contextual cues contribute to drug craving and relapse after abstinence, which is a major challenge to drug addiction treatment.”

Key finding: Our study suggests that inhibition of actin polymerization during drug memory reconsolidation may be a potential approach to prevent drug relapse.

Scientific Reports • 05 Nov 2015 • Research

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Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats

This article may help explain addiction science through research on cocaine, craving, relapse, treatment. The source abstract begins by describing: “Relapse to drug use after abstinence is a major challenge in treating substance use disorder.”

Key finding: Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.

Translational Psychiatry • 27 May 2024 • Research

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