The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex

Ceceli, Ahmet O.; Bradberry, Charles W.; Goldstein, Rita Z.

doi:10.1038/s41386-021-01153-9

Cited by 90 publications

(81 citation statements)

References 276 publications

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“…The main models of treatment for addiction take a multidisciplinary approach that addresses several dimensions of this complex disorder. The treatment may entail detoxification, pharmacological agents ( 4 , 8 ), and psychotherapy, which may include individual, group, and family approaches ( 9 , 10 ). However, the most challenging impediment to treat addiction is that users seldom ask for help.…”

Section: Introductionmentioning

confidence: 99%

“…The disease is essentially inaccessible, namely, self-locking. The use of defenses may entail neurobiological correlates operating in addiction including the modifications of the dopamine mesolimbic pathway and impaired functioning of the prefrontal cortex (PFC), which may contribute to the scarce insight related to the recognition of addiction ( 7 , 8 ) and to the compulsory use of the drug ( 13 ). Behavioral, cognitive, biological, and subjective aspects are coherent in the presentation of addiction.…”

Section: Introductionmentioning

confidence: 99%

“…However, there are important neurobiological implications that contribute to explain the use of the defenses described before. When addictive drugs recruit the mesocortical limbic dopamine pathway, they hijack a system involved in motivation, incentive salience ( 16 , 17 ) and executive functions ( 3 , 8 , 12 ) amongst others. Olds and Milner ( 18 ) named it the reward system as they believed they had found the pleasure centers of the brain.…”

Section: Introductionmentioning

confidence: 99%

“…This type of thinking reduces the chances that users notice their false associations, thus enhancing the risk of addiction while simultaneously decreasing the chances of looking for help. Moreover, Ceceli et al ( 8 ) have recently reviewed the dysfunction of the PFC in addiction. They emphasize the impaired response inhibition and salience attribution (I-RISA) model as proposed by ( 21 ) to explain the difficulties in suppressing disadvantageous behaviors related to overvaluing drug reinforcers and undervaluing reinforcers unrelated to drug use.…”

Section: Introductionmentioning

confidence: 99%

“…Negative affects that strongly motivate toward attempts to find relief are not regulated because of the PFC limitations that originate in the separation distress trauma context. This configuration worsens when the person uses addictive drugs as the PFC will lose more of its functions as a result to the repeated exposure to drugs ( 8 ). Addiction becomes a conflict between protracted negative affects and a weakened PFC emotion regulation function.…”

Section: Introductionmentioning

confidence: 99%

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Affective Neuroscience Contributions to the Treatment of Addiction: The Role of Social Instincts, Pleasure and SEEKING

Mosri

2021

Front. Psychiatry

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Addiction is an illness prevalent in the worldwide population that entails multiple health risks. Because of the nature of addictive disorders, users of drugs seldom look for treatment and when they do, availability can be difficult to access. Permanence in treatment and its outcomes vary from case to case. Most models work from a multidisciplinary approach that tackles several dimensions of addictive disorders. However, the different etiological factors claim for a personalized treatment to enhance opportunities for better results. Problems in relationships with others play an important role in the etiology and the recovery process of addiction. This paper focuses on the social-environmental causes of addiction based on an affective neuroscience approach that attempts to integrate the interplay between social instincts, pleasure, and the SEEKING system in addiction. To advance toward better treatment strategies, it is pertinent to understand the limitations of the current multidisciplinary models. Acknowledging the social nature of the human brain may help to identify the quality of different types of traumatic early life experiences in drug users and how to address them in what may become a neuropsychoanalytic treatment of addiction.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Affective Neuroscience Contributions to the Treatment of Addiction: The Role of Social Instincts, Pleasure and SEEKING

Mosri

2021

Front. Psychiatry

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Frontal White Matter Changes and Craving Recovery in Inpatients With Heroin Use Disorder

Gaudreault,

King,

Huang

et al. 2024

JAMA Netw Open

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ImportanceAmidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. White matter impairments in individuals with heroin use disorder (HUD) have been associated with drug craving, a reliable predictor of treatment outcomes; however, little is known about structural connectivity changes with inpatient treatment and abstinence in individuals with HUD.ObjectiveTo assess white matter microstructure and associations with drug craving changes with inpatient treatment in individuals with HUD (effects of time and rescan compared with controls).Design, Setting, and ParticipantsThis cohort study conducted from December 2020 to September 2022 included individuals recruited from urban inpatient treatment facilities treating HUD and surrounding communities in New York City. Participants with HUD were receiving medication-assisted treatment. Data were analyzed from October 2022 to March 2023.InterventionBetween scans, inpatient individuals with HUD continued treatment and related clinical interventions. Control participants were scanned at similar time intervals.Main Outcomes and MeasuresChanges in white matter diffusion metrics (fractional anisotropy and mean, axial, and radial diffusivities) assessed voxelwise with general linear models in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).ResultsThirty-four individuals with HUD (mean [SD] age, 40.5 [11.0] years; 9 women [36%]; 3 Black [9%], 17 White [50%], 14 other race or ethnicity [41%]) and 25 control (mean [SD] age, 42.1 [9.0]; 7 women [21%]; 8 Black [32%], 10 White [40%], 7 other race or ethnicity [28%]) were included. Main voxelwise findings showed HUD-specific white matter microstructure changes (1 − P &gt; .949), including increased fractional anisotropy and decreased mean and radial diffusivities, encompassing mostly frontal major callosal, projection, and association tracts. The increased fractional anisotropy (r = −0.72, P &lt; .001, slope SE = 9.0 × 10−4) and decreased mean diffusivity (r = 0.69, P &lt; .001, slope SE = 1.25 × 10−6) and/or radial diffusivity (r = 0.67, P &lt; .001, slope SE = 1.16 × 10−6) in the genu and body of the corpus callosum and left anterior corona radiata in individuals with HUD correlated with a reduction in baseline craving (voxelwise 1 − P &gt; .949). No other white matter correlations with outcome variables reached significance.Conclusions and RelevanceThis cohort study of inpatients with HUD on medication-assisted treatment found whole-brain normalization of structural connectivity in frontal white matter pathways implicated in emotional regulation and top-down executive control. Observed associations with decreases in baseline craving further support the possibility of recovery, highlighting the relevance of these white matter markers to a major symptom of addiction, with implications for clinical outcome monitoring.

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Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention

Volkow

Blanco

2023

World Psychiatry

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Substance use disorders (SUDs) are highly prevalent and exact a large toll on individuals' health, well-being, and social functioning. Long-lasting changes in brain networks involved in reward, executive function, stress reactivity, mood, and self-awareness underlie the intense drive to consume substances and the inability to control this urge in a person who suffers from addiction (moderate or severe SUD). Biological (including genetics and developmental life stages) and social (including adverse childhood experiences) determinants of health are recognized factors that contribute to vulnerability for or resilience against developing a SUD. Consequently, prevention strategies that target social risk factors can improve outcomes and, when deployed in childhood and adolescence, can decrease the risk for these disorders. SUDs are treatable, and evidence of clinically significant benefit exists for medications (in opioid, nicotine and alcohol use disorders), behavioral therapies (in all SUDs), and neuromodulation (in nicotine use disorder). Treatment of SUDs should be considered within the context of a Chronic Care Model, with the intensity of intervention adjusted to the severity of the disorder and with the concomitant treatment of comorbid psychiatric and physical conditions. Involvement of health care providers in detection and management of SUDs, including referral of severe cases to specialized care, offers sustainable models of care that can be further expanded with the use of telehealth. Despite advances in our understanding and management of SUDs, individuals with these conditions continue to be stigmatized and, in some countries, incarcerated, highlighting the need to dismantle policies that perpetuate their criminalization and instead develop policies to ensure support and access to prevention and treatment.

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The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex

Cited by 90 publications

References 276 publications

Affective Neuroscience Contributions to the Treatment of Addiction: The Role of Social Instincts, Pleasure and SEEKING

Affective Neuroscience Contributions to the Treatment of Addiction: The Role of Social Instincts, Pleasure and SEEKING

Frontal White Matter Changes and Craving Recovery in Inpatients With Heroin Use Disorder

Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention

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