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Conceptual model of factors that affect treatment effectiveness. Risk factors proposed in the AARDoC, including incentive salience, negative emotionality, executive function, and social environmental factors, are shown in black bold font encircling alcohol use. Contextual risk factors, including decision-making, self-efficacy, pain, craving, etc., are shown in black font in colored boxes. Risk and protective factors overlap with alcohol use and interact in predicting coping regulation and alcohol use among individual patients.
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Alcohol is a major contributor to global disease and a leading cause of preventable death, causing approximately 88,000 deaths annually in the United States alone. Alcohol use disorder is one of the most common psychiatric disorders, with nearly one-third of U.S. adults experiencing alcohol use disorder at some point during their lives. Alcohol use...
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... models proposes factors that may affect treatment effectiveness; however, many of the constructs proposed in each of these models are overlapping and likely contribute to the effectiveness of alcohol use disorder treatment across a range of populations and settings. A heuristic model combining components from each of these models is shown in Fig. 1. Specifically, this model highlights the precipitants of alcohol use that are influenced by the neurobiological adaptations proposed in the addiction cycle (indicated by bold font) and additional contextual factors (regular font) that decrease or increase the likelihood of drinking in context, depending on whether an individual uses ...
Citations
... The authors further discuss that alcohol dysregulates glutamatergic, GABAergic, and neuropeptidergic signaling, similar to the invertebrate models [192]. Furthermore, GABA receptor agonists (Baclofen), GABA analog (Gabapentin), and NMDAR agonists (Acamprosate) have been used as medications to treat alcohol use disorder in clinical studies [193]. Additionally, chronic alcohol exposure decreases BDNF levels in various brain regions and has been associated with increased alcohol drinking and the development of tolerance [194,195]. ...
Alcohol tolerance is a neuroadaptive response that leads to a reduction in the effects of alcohol caused by previous exposure. Tolerance plays a critical role in the development of alcohol use disorder (AUD) because it leads to the escalation of drinking and dependence. Understanding the molecular mechanisms underlying alcohol tolerance is therefore important for the development of effective therapeutics and for understanding addiction in general. This review explores the molecular basis of alcohol tolerance in invertebrate models, Drosophila and C. elegans, focusing on synaptic transmission. Both organisms exhibit biphasic responses to ethanol and develop tolerance similar to that of mammals. Furthermore, the availability of several genetic tools makes them a great candidate to study the molecular basis of ethanol response. Studies in invertebrate models show that tolerance involves conserved changes in the neurotransmitter systems, ion channels, and synaptic proteins. These neuroadaptive changes lead to a change in neuronal excitability, most likely to compensate for the enhanced inhibition by ethanol.
... 3 In the US, AUD is among the most prevalent mental health disorders. 4 Research since 2008 has found that alcohol-related harm is generally increasing among adults, particularly in women, based on the US national data that analyzed trends in alcohol-related harm such as hospitalizations over time. 5 A cross-sectional study utilizing the CDC WONDER database estimated an annual 25% surge in alcohol-induced overall mortality among individuals aged 25-34 and 35-44 from 2018 to 2020. ...
Alcohol use disorder (AUD) is a significant risk factor, accounting for approximately 13% of all deaths in the US. AUD not only destroys families but also causes economic losses due to reduced productivity, absenteeism, and healthcare expenses. Statistics revealing the sustained number of individuals affected by AUD over the years underscore the need for further understanding of the underlying pathophysiology to advance novel therapeutic strategies. Previous research has implicated the limbic brain regions N-methyl-D-aspartate glutamate receptors (NMDAR) in the emotional and behavioral effects of AUD. Given that aerobic exercise can modulate NMDAR activity and sensitivity to alcohol, this review presents a summary of clinical and basic science studies on NMDAR levels induced by alcohol consumption, as well as acute and protracted withdrawal, highlighting the potential role of aerobic exercise as an adjunctive therapy for AUD. Based on our findings, the utility of exercise in the modulation of reward-linked receptors and AUD may be mediated by its effects on NMDA signaling. These data support further consideration of the potential of aerobic exercise as a promising adjunctive therapy for AUD.
... When manualized, theory-based therapies are compared in head-to-head trials, no single approach demonstrates superiority. However, brief interventions and motivational enhancement approaches are generally best for those with at-risk drinking or mild AUD, whereas more intensive approaches are best for those with moderate-to-severe AUD 111 . Harm reduction therapy approaches also lead to reduction in alcohol use and AUD symptoms in randomized controlled trials 112,113 . ...
... For example, genetics and family history of alcoholism are uncontrollable risk factors for alcoholism that increase the chance of alcoholism greatly. On the other hand, controllable factors can be like, being exposed at a young age to stress and trauma, and consuming alcohol early in life [3]. Misusing alcohol results in a massive impact on health. ...
... Naltrexone was the last drug to be approved by FDA in 1994. From that time till now there have been some drugs that were made but not approved by FDA that are used in some countries like, Baclofen [3]. The drugs approved by FDA are used till now, but each drug has its benefit in its own way, and they show variability in the treatment response [4]. ...
... When AD has developed, screening, diagnosis, and treatment are essential for preventing or minimizing serious negative medical and social consequences. Specific behavioral as well as pharmacological treatments for AD have solid support in evidence (12), and the combination of pharmacotherapy with evidence-based behavioral interventions is superior to pharmacotherapy combined with treatment as usual (13). Despite these developments in evidence-based interventions, only about 1 in 6 people with AD ever receive treatment, and then only years after meeting diagnostic criteria (14)(15)(16). ...
... Medications currently approved for the treatment of AD in Europe and the United States, as well as those with sufficient evidence to support off-label use have been reviewed (12,18,19) and will only be mentioned briefly here. Approved medications target three distinct mechanisms. ...
Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems.
... According to SAMHSA data obtained between October 2020 and December 2020, an estimated 25.9 million past-year alcohol users and 10.9 million past-year drug users reported a significant increase in use from the onset of COVID-19 outbreak [4]. Despite advances in the treatment of individuals with SUD [5], the burden of morbidity and mortality associated with SUD continues to rise, with a significant risk of acquiring communicable diseases such as HIV/AIDS and hepatitis B and C among users who engage in risky behaviors such as needle sharing and unprotected sexual activities [6]. ...
Background and Objective: Substance use disorders (SUD) remain a major public health concern and represent a significant cause of morbidity and mortality. Our goal in this study is to explore and determine the effect(s) of employment-based contingency (EBC) on enrolling SUD individuals into treatment, the rate of treatment adherence, and the rate of post-treatment abstinence. Methods: PubMed and Google Scholar search was conducted using the search terms ((substance use disorder) AND (unemployment)) OR (therapeutic workplace)), for randomized controlled trials (RCT) published between 2012 and 2022, reporting on participants between ages 18 and 65 years who use opioids, cocaine or alcohol. Results: Seven RCT which met the criteria and addressed the study objectives had a total of 389 participants. Three RCT of the seven with 203 participants found EBC to positively impact the rate of enrollment to treatment with 100%, 92%, and 100% enrollment rates in the respective studies. Three articles with 172 participants found a higher rate of treatment adherence and retention to treatment among EBC participants compared to the control group. There was more naltrexone-positive urine in the EBC group compared to control (72% vs. 21%, with a p-value of .01), and 74% (EBC) vs 26% (control) participants completed treatment. Four articles with 238 participants found that EBC improved the rate of abstinence by over 50%, which is double the rate among the control group without EBC. Conclusion: EBC is effective in improving SUD treatment enrollment, treatment adherence, and post-treatment abstinence, however, the efficacy may be dependent on how much is earned as an incentive.
... Relapse prevention is a significant challenge in treating AUD [1,2], and is often driven by cue-induced cravings, caused by re-exposure to alcohol-associated cues [3][4][5][6][7]. Thus, disruption of the memories for the cue-alcohol association is expected to suppress cueinduced relapse. ...
... As shown in Figure 1B,D,F, retrieval of alcohol memory did not affect the phosphorylation levels of AKT, GSK3β, and CRMP2 (one-way ANOVA: mPFC: pAKT (Thr308) [F (2,29) The levels of the total CRMP2 protein were mostly unaffected as well, except for a mild reduction observed in the amygdala 30 min after alcohol memory retrieval (Figures 1C,E Since activation of mTORC1 was previously observed in the OFC following exposure to a context that was associated with alcohol self-administration, we also investigated this region. However, no changes in the inspected proteins were observed ( Figure S4). ...
Relapse to alcohol abuse, often caused by cue-induced alcohol craving, is a major challenge in alcohol addiction treatment. Therefore, disrupting the cue-alcohol memories can suppress relapse. Upon retrieval, memories transiently destabilize before they reconsolidate in a process that requires protein synthesis. Evidence suggests that the mammalian target of rapamycin complex 1 (mTORC1), governing the translation of a subset of dendritic proteins, is crucial for memory reconsolidation. Here, we explored the involvement of two regulatory pathways of mTORC1, phosphoinositide 3-kinase (PI3K)-AKT and extracellular regulated kinase 1/2 (ERK1/2), in the reconsolidation process in a rat (Wistar) model of alcohol self-administration. We found that retrieval of alcohol memories using an odor-taste cue increased ERK1/2 activation in the amygdala, while the PI3K-AKT pathway remained unaffected. Importantly, ERK1/2 inhibition after alcohol memory retrieval impaired alcohol-memory reconsolidation and led to long-lasting relapse suppression. Attenuation of relapse was also induced by post-retrieval administration of lacosamide, an inhibitor of collapsin response mediator protein-2 (CRMP2)—a translational product of mTORC1. Together, our findings indicate the crucial role of ERK1/2 and CRMP2 in the reconsolidation of alcohol memories, with their inhibition as potential treatment targets for relapse prevention.
... Despite the existence of various therapies developed for assisting people with this disorder [6,7], there is currently no scientific consensus on what alcohol addiction recovery means beyond substance use control. Its definition is still debated among clinicians, researchers, and organizations, who describe it as a "state" [8], a "lifestyle" [9], an "experience" [10], or a "process" characterized by an increase in well-being or quality of life [11][12][13][14][15][16][17]. ...
b> Introduction: Currently, there is no scientific consensus on the concept of alcohol addiction recovery beyond substance use control. This conceptual issue challenges the implementation of therapeutic strategies and mental health policies that are unrestricted to symptomatic remission. Aiming to contribute to its definition, this study aimed to examine the recovery experience of individuals with alcohol addiction using dialectical phenomenological psychopathology (DPP) as a theoretical and methodological framework. Methods: A dialectical phenomenological analysis was conducted through an examination of online interviews with eight Brazilian, São Paulo state citizens who were self-declared to be undergoing alcohol addiction recovery (or who declared that they had completely recovered). Results: Participants’ reports generated eight categories that were subdivided into two groups. The first group indicated experiential elements of recovery, such as changes in self-relation, changes in interpersonal relations, and changes in time relations, giving new meanings to suffering and alcohol use, and recovery as a continuous process. The second group referred to how the participants interpreted recovery according to their worldviews: as a spiritual experience, moral reformation, and mentality change. Conclusion: These categories can be understood through the lens of DPP as a process of change in the subjects’ being in the world, characterized by the continued management of their existential imbalances in the dimensions of spatiality, temporality, selfhood, and intersubjectivity. The results are preliminary when it comes to conceptualizing recovery but may help future studies to develop recovery-oriented therapeutic strategies.
... The most common mental disorder is alcohol use disorder (AUD), a condition characterized by an impaired ability to stop or control alcohol use despite adverse social and health consequences. Persistent changes in the KP caused by alcohol abuse are suspected to perpetuate AUD and make individuals vulnerable to relapse [6,7]. Recent discoveries have shown clear implications of the KP for AUD [8]. ...
In recent years, there has been a marked increase in interest in the role of the kynurenine pathway (KP) in mechanisms associated with addictive behavior. Numerous reports implicate KP metabolism in influencing the immune system, hypothalamic–pituitary–adrenal (HPA) axis, and neurotransmission, which underlie the behavioral patterns characteristic of addiction. An in-depth analysis of the results of these new studies highlights interesting patterns of relationships, and approaching alcohol use disorder (AUD) from a broader neuroendocrine–immune system perspective may be crucial to better understanding this complex phenomenon. In this review, we provide an up-to-date summary of information indicating the relationship between AUD and the KP, both in terms of changes in the activity of this pathway and modulation of this pathway as a possible pharmacological approach for the treatment of AUD.
... AUD is diagnosed as a pattern of excessive alcohol consumption with repeated cycles of abstinence followed by resumption of heavy drinking, which in turn leads to negative psychological, physical, and social consequences [1]. This phenotype has been captured in a rhesus monkey model of alcohol self-administration using repeated cycles of chronic voluntary ethanol drinking and prolonged abstinence [2]. ...
Male rhesus monkeys ( n = 24) had a biopsy of prefrontal cortical area 46 prior to chronic ethanol self-administration ( n = 17) or caloric control ( n = 7). Fourteen months of daily self-administration (water vs. 4% alcohol, 22 h access/day termed “open-access”) was followed by two cycles of prolonged abstinence (5 weeks) each followed by 3 months of open-access alcohol and a final abstinence followed by necropsy. At necropsy, a biopsy of Area 46, contralateral to the original biopsy, was obtained. Gene expression data (RNA-Seq) were collected comparing biopsy/necropsy samples. Monkeys were categorized by drinking status during the final post-abstinent drinking phase as light (LD), binge (BD), heavy (HD) and very heavy (VHD drinkers). Comparing pre-ethanol to post-abstinent biopsies, four animals that converted from HD to VHD status had significant ontology enrichments in downregulated genes (necropsy minus biopsy n = 286) that included immune response (FDR < 9 × 10 ⁻⁷ ) and plasma membrane changes (FDR < 1 × 10 ⁻⁷ ). Genes in the immune response category included IL16 and 18 , CCR1 , B2M , TLR3 , 6 and 7 , SP2 and CX3CR1 . Upregulated genes ( N = 388) were particularly enriched in genes associated with the negative regulation of MAP kinase activity (FDR < 3 × 10 ⁻⁵ ), including DUSP 1 , 4 , 5 , 6 and 18 , SPRY 2 , 3 , and 4 , SPRED2 , BMP4 and RGS2 . Overall, these data illustrate the power of the NHP model and the within-subject design of genomic changes due to alcohol and suggest new targets for treating severe escalated drinking following repeated alcohol abstinence attempts.
