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Physiological Reviews Oct 2019Drug consumption is driven by a drug's pharmacological effects, which are experienced as rewarding, and is influenced by genetic, developmental, and psychosocial factors... (Review)
Review
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.
Topics: Animals; Behavior, Addictive; Brain; Dopaminergic Neurons; Drug Users; Humans; Neural Pathways; Neuronal Plasticity; Reward; Risk Factors; Substance-Related Disorders
PubMed: 31507244
DOI: 10.1152/physrev.00014.2018 -
Cold Spring Harbor Perspectives in... Apr 2021Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss... (Review)
Review
Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide an overview of various theories of addiction to drugs of abuse and the neurobiology involved in elements of the addiction cycle. Specific focus is devoted to the role of the mesolimbic pathway in acute drug reinforcement and occasional drug use, the role of the mesocortical pathway and associated areas (e.g., the dorsal striatum) in escalation/dependence, and the contribution of these pathways and associated circuits to conditioned responses, drug craving, and loss of behavioral control that may underlie drug relapse. By enhancing the understanding of the neurobiological factors that mediate drug addiction, continued preclinical and clinical research will aid in the development of novel therapeutic interventions that can serve as effective long-term treatment strategies for drug-dependent individuals.
Topics: Behavior, Addictive; Disease Progression; Humans; Neurobiology; Recurrence; Substance-Related Disorders
PubMed: 32205414
DOI: 10.1101/cshperspect.a039628 -
Archives de Pediatrie : Organe Officiel... Nov 2020Substance abuse (SA) among children is a recognized challenge for policymakers and law enforcement and has life-threatening consequences owing to the impact on the... (Review)
Review
Substance abuse (SA) among children is a recognized challenge for policymakers and law enforcement and has life-threatening consequences owing to the impact on the children's development and the consequent increase in vulnerability. This work outlines several important issues related to SA among children: (1) SA prevalence including onset, common examples, extent, and spectrum of SA; (2) the presence of new psychoactive substances, which are rapidly spreading worldwide with limitations regarding their prevalence, detection, and interventions; (3) street children and their recruitment in drug supply; (4) SA and substance use disorder pathways, risk and protective factors for the development of SA; (5) SA consequences in the case of early initiation, including deaths; and (6) current preventive interventions for the pediatric population. In conclusion, this challenge requires consistent and unremitting attention in order to execute effective prevention programs with continuous re-evaluation of the situation.
Topics: Adolescent; Adolescent Health; Child; Child Health; Child Welfare; Global Health; Homeless Youth; Humans; Prevalence; Protective Factors; Risk Factors; Substance-Related Disorders
PubMed: 33011026
DOI: 10.1016/j.arcped.2020.09.006 -
Drug and Alcohol Dependence Jul 2019Benzodiazepine misuse is a growing public health problem, with increases in benzodiazepine-related overdose deaths and emergency room visits in recent years. However,...
BACKGROUND
Benzodiazepine misuse is a growing public health problem, with increases in benzodiazepine-related overdose deaths and emergency room visits in recent years. However, relatively little attention has been paid to this emergent problem. We systematically reviewed epidemiological studies on benzodiazepine misuse to identify key findings, limitations, and future directions for research.
METHODS
PubMed and PsychINFO databases were searched through February 2019 for peer-reviewed publications on benzodiazepine misuse (e.g., use without a prescription; at a higher frequency or dose than prescribed). Eligibility criteria included human studies that focused on the prevalence, trends, correlates, motives, patterns, sources, and consequences of benzodiazepine misuse.
RESULTS
The search identified 1970 publications, and 351 articles were eligible for data extraction and inclusion. In 2017, benzodiazepines and other tranquilizers were the third most commonly misused illicit or prescription drug in the U.S. (approximately 2.2% of the population). Worldwide rates of misuse appear to be similar to those reported in the U.S. Factors associated with misuse include other substance use, receipt of a benzodiazepine prescription, and psychiatric symptoms and disorders. Benzodiazepine misuse encompasses heterogeneous presentations of motives, patterns, and sources. Moreover, misuse is associated with myriad poor outcomes, including mortality, HIV/HCV risk behaviors, poor self-reported quality of life, criminality, and continued substance use during treatment.
CONCLUSIONS
Benzodiazepine misuse is a worldwide public health concern that is associated with a number of concerning consequences. Findings from the present review have implications for identifying subgroups who could benefit from prevention and treatment efforts, critical points for intervention, and treatment targets.
Topics: Benzodiazepines; Drug Overdose; Humans; Prescription Drug Misuse; Prescription Drugs; Prevalence; Public Health; Quality of Life; Substance-Related Disorders
PubMed: 31121495
DOI: 10.1016/j.drugalcdep.2019.02.033 -
Journal of Child and Adolescent... Aug 2019While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a... (Review)
Review
While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a substance use disorder (SUD). Pharmacotherapy, in combination with behavioral interventions, has the potential to increase the likelihood of successful treatment for youth struggling with SUD; however, the literature in this area is limited. To date, there are no Food and Drug Administration (FDA)-approved medications for adolescent SUD, other than buprenorphine, which has been approved down to 16 years of age for opioid use disorder. Despite alcohol and cannabis being the most commonly used substances during adolescence, only three medications have been tested among this demographic, and only two have warranted further study (i.e., naltrexone for alcohol and -acetylcysteine for cannabis use disorder). Although less common in adolescents and young adults, the most promising pharmacological findings for this age group are for opioid (buprenorphine) and tobacco (bupropion and varenicline) use disorders. In addition, despite the recent marked increases in electronic nicotine delivery systems (i.e., vaping) among youth, treatment strategies are still in their infancy and no recommendation exists for how to promote cessation for youth vaping. Current findings are limited by: small, demographically homogeneous samples; few trials, including a substantial number of youth younger than 18; low retention; medication adherence rates; and minimal information on effective dosing levels and long-term outcomes. Overall, pharmacotherapy may be a potentially effective strategy to increase treatment effects; however, more rigorous research trials are warranted before FDA approval would be granted for any of the potential adjunctive medications in this age group.
Topics: Adolescent; Age Factors; Alcoholism; Behavior Therapy; Combined Modality Therapy; Humans; Medication Adherence; Smoking Cessation; Substance-Related Disorders; Tobacco Use Disorder; Young Adult
PubMed: 31009234
DOI: 10.1089/cap.2019.0009 -
CNS Drugs Apr 2020Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.
METHODS
We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.
RESULTS
Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.
CONCLUSIONS
No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Central Nervous System Stimulants; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 32185696
DOI: 10.1007/s40263-020-00711-x -
Medicina 2020Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental alteration of biological basis that started in childhood may persist during adolescence-youth... (Review)
Review
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental alteration of biological basis that started in childhood may persist during adolescence-youth and, despite what was believed until not many years ago, also in adulthood up to 50-60% of those affected, producing a significant clinical and psychosocial deterioration. In spite of being a syndrome easily identifiable by the triad: inattention, hyperactivity and impulsivity that characterizes it, in clinical practice there are different circumstances that hinder and complicate its diagnosis and treatment. One of the most significant is the presence, both in childhood and adulthood, of other comorbid mental disorders. It is from adolescence-youth when together with ADHD we can detect the presence of personality, mood and anxiety disorders and especially the use of several substances. The evidences existing until now show how the comorbidity of ADHD and substance use disorder influence the evolutionary course of both, complicating the approach, the treatment and, therefore, aggravating the final prognosis. The difficulties in their approach and the scarcity of treatment options make us underline the importance of preventive treatment in the infantile stage, starting from psychoeducation programs focused on the vulnerability of these patients to substances and the consequences associated with consumption.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Child; Diagnostic and Statistical Manual of Mental Disorders; Humans; Risk Factors; Substance-Related Disorders; Young Adult
PubMed: 32150719
DOI: No ID Found -
Psychotherapy and Psychosomatics 2022Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory... (Review)
Review
Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.
Topics: Alcoholism; Anxiety; Benzodiazepines; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 35504267
DOI: 10.1159/000524400 -
Medicina (Kaunas, Lithuania) Nov 2021Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use... (Review)
Review
Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.
Topics: Alcoholism; Bipolar Disorder; Comorbidity; Humans; Psychotropic Drugs; Substance-Related Disorders
PubMed: 34833474
DOI: 10.3390/medicina57111256 -
Tidsskrift For Den Norske Laegeforening... Sep 2019
Topics: Adolescent; Aftercare; Alcoholic Intoxication; Ambulatory Care Facilities; Dangerous Behavior; Humans; Substance-Related Disorders; Young Adult
PubMed: 31556530
DOI: 10.4045/tidsskr.19.0513