Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms ...of this condition and its co-option of pathways regulating reward, self-control, and affect. Drugs of abuse exert their initial reinforcing effects by triggering supraphysiologic surges of dopamine in the nucleus accumbens that activate the direct striatal pathway via D1 receptors and inhibit the indirect striato-cortical pathway via D2 receptors. Repeated drug administration triggers neuroplastic changes in glutamatergic inputs to the striatum and midbrain dopamine neurons, enhancing the brain’s reactivity to drug cues, reducing the sensitivity to non-drug rewards, weakening self-regulation, and increasing the sensitivity to stressful stimuli and dysphoria. Drug-induced impairments are long lasting; thus, interventions designed to mitigate or even reverse them would be beneficial for the treatment of addiction.
Addiction is a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms of this condition and its co-option of pathways regulating reward, self-control, and affect.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The opioid crisis in the United States has brought drug addiction to the forefront of the public mind and to the attention of health care personnel, organizations, and agencies. The epidemic of ...overdoses, beginning with those caused by prescription opioid analgesics and then broadening to include heroin and fen t any I and its analogs, has prompted major initiatives in local communities, states, and at the federal level to treat addiction and pain more effectively. The crisis has highlighted an insulated addiction treatment s\s-tem that for decades was segregated from the rest of health care because of stigma associated with addiction and. by extension, the medications used to treat it. Stigmatizing attitudes have been slow to erode, but the moralizing and punitive viewpoints of the past are gradually giving way to a medical and even a cultural consensus that addiction is a chronic disorder of the brain, one that is strongly influenced by social factors, and one that is also treatable.
The current opioid epidemic is one of the most severe public health crisis in US history. Responding to it has been difficult due to its rapidly changing nature and the severity of its associated ...outcomes. This review examines the origin and evolution of the crisis, the pharmacological properties of opioids, the neurobiology of opioid use and opioid use disorder (OUD), medications for opioid use disorder (MOUD), and existing and promising approaches to prevention. The results of the review indicate that the opioid epidemic is a complex, evolving phenomenon that involves neurobiological vulnerabilities and social determinants of health. Successfully addressing the epidemic will require advances in basic science, development of more acceptable and effective treatments, and implementation of public health approaches, including prevention. The advances achieved in addressing the current crisis should also serve to advance the science and treatment of other substance use disorders.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Stigma and the Toll of Addiction Volkow, Nora D
The New England journal of medicine,
04/2020, Volume:
382, Issue:
14
Journal Article
Peer reviewed
Open access
Among the challenges in delivering appropriate care to the millions of people in the United States with substance use disorder is the chilling effect of stigma. Stigma impedes access to treatment and ...care delivery and contributes to the disorder on the individual level.
Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, ...and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
Drug consumption is driven by a drug's pharmacological effects, which are experienced as rewarding, and is influenced by genetic, developmental, and psychosocial factors that mediate drug ...accessibility, norms, and social support systems or lack thereof. The reinforcing effects of drugs mostly depend on dopamine signaling in the nucleus accumbens, and chronic drug exposure triggers glutamatergic-mediated neuroadaptations in dopamine striato-thalamo-cortical (predominantly in prefrontal cortical regions including orbitofrontal cortex and anterior cingulate cortex) and limbic pathways (amygdala and hippocampus) that, in vulnerable individuals, can result in addiction. In parallel, changes in the extended amygdala result in negative emotional states that perpetuate drug taking as an attempt to temporarily alleviate them. Counterintuitively, in the addicted person, the actual drug consumption is associated with an attenuated dopamine increase in brain reward regions, which might contribute to drug-taking behavior to compensate for the difference between the magnitude of the expected reward triggered by the conditioning to drug cues and the actual experience of it. Combined, these effects result in an enhanced motivation to "seek the drug" (energized by dopamine increases triggered by drug cues) and an impaired prefrontal top-down self-regulation that favors compulsive drug-taking against the backdrop of negative emotionality and an enhanced interoceptive awareness of "drug hunger." Treatment interventions intended to reverse these neuroadaptations show promise as therapeutic approaches for addiction.
Aberrant patterns of brain functional connectivity in the default mode network (DMN) have been observed across different classes of substance use disorder (SUD) and are associated with craving and ...relapse. In addicted individuals resting functional connectivity (RSFC) of the anterior DMN, which participates in attribution of personal value and emotional regulation, tends to be decreased, whereas RSFC of the posterior DMN, which directs attention to the internal world, tends to be increased. Aberrant RSFC within the DMN is believed to contribute to impaired self-awareness, negative emotions and to ruminations in addiction. Additionally, the disrupted connectivity between DMN and cortical regions involved with executive function, memory and emotion could be critical to drug-taking regardless of negative consequences and to stress-triggered relapse. At the system level, the dynamics of DMN interactions with the executive control and the salience networks are also disturbed in addiction. The DMN is prominently engaged during the withdrawal and preoccupation phases of the addiction cycle at the expense of the executive control network and with an enhanced participation of the salience network. In contrast, DMN prominence appears to be transitorily decreased during the intoxication phases. There is also growing evidence that disruption of the DMN in addiction reflects in part changes in dopaminergic, glutamatergic, and GABAergic signaling associated with acute and chronic drug use. Findings are starting to reveal DMN RSFC as a potential biomarker for predicting clinical outcomes in SUD and identify the DMN as a promising target for the treatment of addiction.
•Drug abuse alters DMN connectivity affecting cognitive and emotional processing.•Acute and chronic drug use have different effects on DMN.•Aberrant connectivity of DMN to other regions affects self-related decisions.•DMN loses dynamic interaction with other networks facilitating craving and relapse.•DA dysfunction in drug abusers contributes to DMN dysfunction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The National Institutes of Health will work with private partners to develop better overdose-reversal and prevention interventions; find new medications and technologies to treat opioid addiction; ...and find safe, effective, nonaddictive strategies to manage chronic pain.
Opioid use disorder is characterised by the persistent use of opioids despite the adverse consequences of its use. The disorder is associated with a range of mental and general medical comorbid ...disorders, and with increased mortality. Although genetics are important in opioid use disorder, younger age, male sex, and lower educational attainment level and income, increase the risk of opioid use disorder, as do certain psychiatric disorders (eg, other substance use disorders and mood disorders). The medications for opioid use disorder, which include methadone, buprenorphine, and extended-release naltrexone, significantly improve opioid use disorder outcomes. However, the effectiveness of medications for opioid use disorder is limited by problems at all levels of the care cascade, including diagnosis, entry into treatment, and retention in treatment. There is an urgent need for expanding the use of medications for opioid use disorder, including training of health-care professionals in the treatment and prevention of opioid use disorder, and for development of alternative medications and new models of care to expand capabilities for personalised interventions.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
