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- Augier, Eric
(författare)
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Recent Advances in the Potential of Positive Allosteric Modulators of the GABA(B) Receptor to Treat Alcohol Use Disorder
- 2021
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press. - 0735-0414 .- 1464-3502. ; 56:2, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The effects of alcohol on gamma-aminobutyric acid (GABA) transmission are key for the development and maintenance of alcohol use disorder (AUD). Previous research consistently indicates that GABA(B) receptor agonists such as baclofen can attenuate addiction-related behaviors in preclinical models of AUD. More importantly, baclofen has also shown promise in clinical studies, particularly in severely alcohol-dependent patients. However, despite this promise, other clinical studies have not confirmed its efficacy and chiefly, larger clinical trials have not been conducted. Therefore, with the exception of France, baclofen is not approved for the treatment of AUD in any other country. Furthermore, it is also important to keep in mind that some patients treated with baclofen may experience important side-effects, including sedation, drowsiness and sleepiness. Methods: This short review will first discuss the history of baclofen for AUD treatment. We will then summarize preclinical behavioral results that have investigated the efficacy of GABA(B) PAMs for addiction treatment, with a special focus on our recent work that investigated the effects of ADX71441, a novel GABA(B) PAM, on several alcohol-related behaviors in rats that model important aspects of human AUD. Finally, in light of the recent criticism about the translational value of animal models of addiction, the specific translational potential of our work and of other preclinical studies that have unanimously reported the efficacy of GABA(B) PAMs to attenuate multiple alcohol-related behaviors will be discussed. Results: Positive allosteric modulators (PAMs) of the GABA(B) receptor offer an attractive alternative approach to baclofen and have the potential to achieve mechanistic and therapeutic effects similar to GABA(B) agonists, while avoiding the tolerance and toxicity issues associated with baclofen. To date, all preclinical behavioral results have invariably shown the efficacy of GABA(B) PAMs for addiction treatment. Conclusions: Preclinical studies indicate that GABA(B) PAMs have a higher therapeutic index than orthosteric agonists, at least in terms of mitigating the sedative effects of GABA(B) agonism. This predicts that GABA(B) PAMs have a high translational potential in humans and merit being tested clinically, in particular in patients with severe AUD.
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| 4. |
- Bendtsen, Preben, et al.
(författare)
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Hazardous drinking concepts, limits and methods : Low levels of awareness, knowledge and use in the Swedish population
- 2011
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Ingår i: Alcohol and Alcoholism. - Oxford, UK : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 46:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the awareness and knowledge of hazardous drinking limits among the general population in Sweden and the extent to which people estimate their alcohol consumption in standard drinks to assess their level of drinking. Methods: A population-based study involving 6000 individuals selected from the total Swedish population was performed. Data were collected by means of a postal questionnaire. The mail survey response rate was 54.3% (n = 3200) of the net sample of 5891 persons. Results: With regard to drinking patterns, 10% of the respondents were abstainers, 59% were sensible drinkers and 31% were classified as hazardous drinkers. Most of the abstainers (80%), sensible drinkers (64%) and hazardous drinkers (56%) stated that they had never heard about the standard drink method. Familiarity with the hazardous drinking concept also differed between the three categories although 61% of sensible and hazardous drinkers expressed awareness of the concept (46% of the abstainers). Knowledge about the limits for sensible drinking was very poor. Between 94 and 97% in the three categories did not know the limit. There was a statistically significant association between having visited health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits. Similarly, there was a significant association between having had at least one alcohol conversation in health care within the last 12 months and being aware of the standard drink method and the hazardous drinking concept, but not with knowing the hazardous drinking limits. Conclusion: The results can be seen as a major challenge for the health-care system and public health authorities because they imply that a large proportion of the Swedish population does not know when alcohol consumption becomes a threat to their health. The current strategy to disseminate knowledge about sensible drinking limits to the population through the health-care system seems to have failed and new means of informing the population are warranted. © The Author 2011. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.
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| 5. |
- Bendtsen, Preben, et al.
(författare)
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Professional's Attitudes Do Not Influence Screening and Brief Interventions Rates for Hazardous and Harmful Drinkers: Results from ODHIN Study
- 2015
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 50:4, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- To determine the relation between existing levels of alcohol screening and brief intervention rates in five European jurisdictions and role security and therapeutic commitment by the participating primary healthcare professionals. Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psychologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities as part of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment. The only significant but small relationship was found between role security and screening rate in a multilevel logistic regression analysis adjusted for occupation of the provider, number of eligible patients and the random effects of jurisdictions and primary health care units (PHCU). No significant relationship was found between role security and brief intervention rate nor between therapeutic commitment and screening rate/brief intervention rate. The proportion of patients screened varied across jurisdictions between 2 and 10%. The findings show that the studied factors (role security and therapeutic commitment) are not of great importance for alcohol screening and BI rates. Given the fact that screening and brief intervention implementation rate has not changed much in the last decade in spite of increased policy emphasis, training initiatives and more research being published, this raises a question about what else is needed to enhance implementation.
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| 6. |
- Carlfjord, Siw, et al.
(författare)
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Association Between Frequency of Heavy Episodic Drinking and Self-reported Consequences: A Cross-sectional Study in a Swedish Population
- 2012
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP): Policy B. - 0735-0414 .- 1464-3502. ; 47:6, s. 719-724
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To describe perceived negative consequences (PNCs) of alcohol consumption related to the frequency of heavy episodic drinking (HED) in a Swedish population attending primary health care (PHC). Methods: Data from a computer-based assessment, including questions about alcohol consumption and PNC, were collected from 28 PHC centres in Sweden. The analysis included 4559 responders. Risk ratios concerning PNC for different frequencies of HED were calculated. Results: Engaging in HED once a month for women and two to three times a month for men significantly raised the proportion of individuals reporting PNC, compared with engaging in HED less than once a month. The men reported PNC of alcohol consumption to a higher degree than the women, and in general, the proportion of individuals reporting PNC was associated with the frequency of HED. Conclusion: Engaging in HED once a month for women and two to three times a month for men are critical levels regarding PNC of alcohol consumption. To identify a cut-off value for categorizing individuals as hazardous alcohol consumers due to the frequency of HED, further studies are needed.
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| 7. |
- Collier, Elizabeth S, et al.
(författare)
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Satisfaction with a digital support tool targeting alcohol consumption : perspectives from participants in a randomized control trial
- 2024
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press. - 0735-0414 .- 1464-3502. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Intervention design may be improved through evaluating the feedback from those who have been exposed to such interventions. As such, here the perspectives of the intervention group from a recent randomized control trial investigating the effectiveness of a digital alcohol intervention, in terms of perceived suitability and usefulness of the support tool they engaged with, were investigated. Methods: Respondents (N=475; 45% of the intervention group) answered five quantitative questions addressing user experience, completed the 10-item System Useability Scale, and were offered the opportunity to write free-text feedback. Quantitative measures were analysed using ordinal and linear regression with baseline characteristics as predictors, and free-text responses were evaluated using content analysis. Results: Overall, respondents were positive towards the intervention in terms of it fitting their needs, the usefulness of the tools included, and the usefulness of text message content. The intervention was perceived as more helpful by respondents with lower total weekly alcohol consumption, higher self-reported confidence in their ability to reduce their drinking, and the perceived importance there of, at baseline. The free-text comments revealed the value of reminders as prompts to reflect on one’s own drinking behaviour. Nonetheless, criticisms of the intervention were voiced, primarily highlighting the repetitive nature of the reminders and the lack of individuation in advice. Some also feltlike the intervention was impersonal and targeted only a specific drinking pattern. Conclusions: Experiences of the intervention group in this trial were generally positive, though there may be demand for more individualised, targeted intervention design.
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| 8. |
- Cortes, Carlos R., et al.
(författare)
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Insula Sensitivity to Unfairness in Alcohol Use Disorder
- 2018
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Ingår i: Alcohol and Alcoholism. - : OXFORD UNIV PRESS. - 0735-0414 .- 1464-3502. ; 53:3, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Social decision making has recently been evaluated in alcohol use disorder (AUD) using the ultimatum game (UG) task, suggesting a possible deficit in aversive emotion regulation elicited by the unfairness during this task. Despite the relevance to relapse of this possible faulty regulation, the brain correlates of the UG in AUD are unknown. Methods: In total, 23 AUD and 27 healthy controls (HC) played three consecutive fMRI runs of the UG, while behavioral and brain responses were recorded. Results: Overall, acceptance rate of unfair offers did not differ between groups, but there was a difference in the rate of behavioral change across runs. We found significant anterior insula (aINS) activation in both groups for both fair and unfair conditions, but only HC showed a trend towards increased activation during unfair vs. fair offers. There were not overall whole-brain between-group significant differences. We found a trend of signal attenuation, instead of an increase, in the aINS for AUD when compared to HC during the third run, which is consistent with our recent findings of selective insula atrophy in AUD. Conclusion: We found differential group temporal dynamics of behavioral response in the UG. The HC group had a low acceptance rate for unfair offers in the first two runs that increased markedly for the third run; whereas the AUD group was consistent in their rejection of unfair offers across the three runs. We found a strong significant decrease in neural response across runs for both groups. Short summary: This fMRI study of UG in alcohol use disorder found behavioral group differences in acceptance rate across runs, which together with significant BOLD-signal decrease across runs in UG-related regions in both groups, highlights the impairment of strategy in AUD and the effect of repetitive exposure to unfairness in this task.
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| 9. |
- Crawford, Joel, et al.
(författare)
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Individualized treatment effects of a digital alcohol intervention and their associations with participant characteristics and engagement
- 2024
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Ingår i: Alcohol and Alcoholism. - : OXFORD UNIV PRESS. - 0735-0414 .- 1464-3502. ; 59:5
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Tidskriftsartikel (refereegranskat)abstract
- Aims Conditional average treatment effects are often reported in intervention studies, in which assumptions are made regarding how effects are similar across a heterogeneous sample. Nonetheless, differing factors, such as genetics, age, and sex, can impact an intervention's effect on outcomes. The study aimed to estimate the individualized effects of a digital alcohol intervention among individuals looking online to reduce their drinking.Methods We used data from a randomized controlled trial (RCT), including 2129 adults from the Swedish general population. The RCT concerned a text message-based alcohol intervention that sought to engender change through increasing knowledge on how to change and instilling confidence in changing behaviour. Outcomes were total weekly alcohol consumption and monthly heavy episodic drinking. Individualized treatment effects were modelled using baseline characteristics (age, gender, alcohol consumption, and psychosocial variables) and engagement with the intervention content.Results We found evidence that the effects of the digital alcohol intervention were heterogeneous concerning participants' age, baseline alcohol consumption, confidence, and importance. For heavy episodic drinking, there was evidence that effects were heterogeneous concerning age, sex, and baseline alcohol consumption. Overall, women, older individuals, and heavier drinkers benefitted more from the intervention in terms of effect size. In addition, participants who engaged more with the goal-setting and screening content reported better outcomes.Conclusions The results highlight how different individuals respond differently to a digital alcohol intervention. This allows insight into who benefits the most and least from the intervention and highlights the potential merit of designing interventions adapted to different individuals' needs. Short Summary: Individualized treatment effects were discernible for older participants, women, and those who consumed higher quantities of alcohol and engaged with more heavy episodic drinking at baseline. Furthermore, those who deemed it of greater import to change behaviour and had more confidence in their ability to change benefited more from the intervention.
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| 10. |
- Domi, Ana, 1990, et al.
(författare)
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Targeting the Opioid Receptors: A Promising Therapeutic Avenue for Treatment in "Heavy Drinking Smokers"
- 2021
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 56:2, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Despite a general decline in tobacco use in the last decades, the prevalence of tobacco smoking in individuals with alcohol use disorder (AUD) remains substantial (45-50%). Importantly, the co-use of both substances potentiates the adverse effects, making it a significant public health problem. Substantial evidence suggests that AUD and Tobacco use disorder (TUD) may share common mechanisms. Targeting these mechanisms may therefore provide more effective therapy. Numerous studies describe a potential role of the endogenous opioid system in both AUD and TUD. Reviewing this literature, we aim to evaluate the efficacy of molecules that target the opioid system as promising therapeutic interventions for treating alcohol and tobacco co-use disorders. Methods: We provide a synthesis of the current epidemiological knowledge of alcohol and tobacco co-use disorders. We evaluate clinical and preclinical research that focuses on the regulation of the endogenous opioid system in alcohol, nicotine, and their interactions. Results: The epidemiological data confirm that smoking stimulates heavy drinking and facilitates alcohol craving. Pharmacological findings suggest that treatments that are efficacious in the dual addiction provide a beneficial treatment outcome in comorbid AUD and TUD. In this regard, MOP, DOP and NOP-receptor antagonists show promising results, while the findings prompt caution when considering KOP-receptor antagonists as a treatment option in alcohol and tobacco co-use disorders. Conclusions: Existing literature suggests a role of the opioid system in sustaining the high comorbidity rates of AUD and TUD. Molecules targeting opioid receptors may therefore represent promising therapeutic interventions in 'heavy drinking smokers.'
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