{"title":"The dopamine 3 receptor as a candidate biomarker and therapeutic for opioid use disorder","authors":"Matthew L. Banks, Jon E. Sprague","doi":"10.1111/adb.13369","DOIUrl":"10.1111/adb.13369","url":null,"abstract":"<p>Here, we present recent studies suggesting that specific <i>DRD3</i> single nucleotide polymorphisms (SNPs, e.g. rs324029 and rs2654754) might serve as prognostic biomarkers for opioid use disorder (OUD). Additionally, preclinical studies with novel dopamine 3 receptor (D3R) partial agonists and antagonists have been evaluated as candidate OUD therapeutics and have shown a reduced risk of cardiovascular toxicity compared with the original D3R antagonist. From these findings, we argue that <i>DRD3</i> SNPs could serve as a diagnostic tool for assessing OUD risk and that more research is warranted examining the D3R as a safe and effective therapeutic target for treating OUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksandra M. Herman, Marek Wypych, Jarosław Michałowski, Artur Marchewka
{"title":"Bodily confusion: Lower differentiation of emotional and physiological states in student alcohol users","authors":"Aleksandra M. Herman, Marek Wypych, Jarosław Michałowski, Artur Marchewka","doi":"10.1111/adb.13364","DOIUrl":"10.1111/adb.13364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alexithymia, difficulty in recognising and naming emotions, is common among people who use alcohol. There is also emerging evidence that people with alexithymia are unable to distinguish emotions from non-emotional physiological states. The project aimed to test if alcohol use is related to the way student drinkers experience emotions and physiological states in the body.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a novel method to study bodily sensations related to emotions and physiological states in the context of alcohol use: the emBODY tool, which allowed participants to mark areas of the body in which they experience various emotions and physiological states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Students who showed a hazardous pattern of alcohol use (alcohol use disorders identification test [AUDIT] score ≥ 7, N = 91), overall, presented higher alexithymia levels and coloured larger areas for emotions and physiological states (showed less specificity) than those who show low-risk alcohol consumption (AUDIT ≤ 4, N = 90). Moreover, statistical classifiers distinguished feeling-specific maps less accurately for hazardous drinkers than low-risk drinkers [<i>F</i>(1,1998) = 441.16; <i>p</i> < 0.001], confirming that higher alcohol use is related to higher confusion of emotional and non-emotional bodily feelings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Plausibly, this increased bodily confusion drives alcohol consumption: alcohol may serve as a means of dealing with undifferentiated changes in psychophysiological arousal accompanying emotional states.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyun Jun Lee, Darlene Mae Ortiz, Leandro Val Sayson, Mikyung Kim, Jae Hoon Cheong, Hee Jin Kim
{"title":"Ameliorating effects of Acanthopanax koreanum extract and components on nicotine dependence and withdrawal symptoms","authors":"Hyun Jun Lee, Darlene Mae Ortiz, Leandro Val Sayson, Mikyung Kim, Jae Hoon Cheong, Hee Jin Kim","doi":"10.1111/adb.13360","DOIUrl":"10.1111/adb.13360","url":null,"abstract":"<p>Tobacco smoking is a serious health problem in society. While smoking rates are declining, smoking remains a serious risk to national health. Currently, there are several medications available to aid in smoking cessation. However, these medications have the disadvantages of low success rates in smoking cessation and various side effects. Therefore, natural-based smoking cessation aids are being suggested as a good alternative due to their accessibility and minimal side effects. The roots and stems of <i>Acanthopanax koreanum</i> (AK) Nakai, a plant that is native to Jeju Island, South Korea, have traditionally been used as tonic and sedatives. Moreover, eleutheroside B and chlorogenic acid are the main components of AK stem extract. In the present study, we investigated the effect of 70% ethanol AK extract and its components on ameliorating nicotine dependence and withdrawal symptoms by using behavioural tests in mice. In addition, alterations in the dopaminergic and DRD1-EPAC-ERK-CREB pathways were observed using dopamine ELISA and western blotting using mouse brains. Our findings demonstrate that the AK extract and its components effectively mitigated the effects of nicotine treatment in behavioural tests. Furthermore, it normalized the dopamine concentration and the expression level of nicotine acetylcholine receptor α7. Additionally, it was observed that AK extract and its components led to the normalization of DRD1, ERK and CREB expression levels. These results indicate that AK extract exhibits effects in ameliorating nicotine dependence behaviour and alleviating withdrawal symptoms. Moreover, EB and CGA are considered potential marker components of AK extract.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepideh Zolfaghari, Yashar Sarbaz, Ali Reza Shafiee-Kandjani
{"title":"Analysing the behaviour change of brain regions of methamphetamine abusers using electroencephalogram signals: Hope to design a decision support system","authors":"Sepideh Zolfaghari, Yashar Sarbaz, Ali Reza Shafiee-Kandjani","doi":"10.1111/adb.13362","DOIUrl":"10.1111/adb.13362","url":null,"abstract":"<p>Long-term use of methamphetamine (meth) causes cognitive and neuropsychological impairments. Analysing the impact of this substance on the human brain can aid prevention and treatment efforts. In this study, the electroencephalogram (EEG) signals of meth abusers in the abstinence period and healthy subjects were recorded during eyes-closed and eyes-opened states to distinguish the brain regions that meth can significantly influence. In addition, a decision support system (DSS) was introduced as a complementary method to recognize substance users accompanied by biochemical tests. According to these goals, the recorded EEG signals were pre-processed and decomposed into frequency bands using the discrete wavelet transform (DWT) method. For each frequency band, energy, KS entropy, Higuchi and Katz fractal dimensions of signals were calculated. Then, statistical analysis was applied to select features whose channels contain a <i>p</i>-value less than 0.05. These features between two groups were compared, and the location of channels containing more features was specified as discriminative brain areas. Due to evaluating the performance of features and distinguishing the two groups in each frequency band, features were fed into a k-nearest neighbour (KNN), support vector machine (SVM), multilayer perceptron neural networks (MLP) and linear discriminant analysis (LDA) classifiers. The results indicated that prolonged consumption of meth has a considerable impact on the brain areas responsible for working memory, motor function, attention, visual interpretation, and speech processing. Furthermore, the best classification accuracy, almost 95.8%, was attained in the gamma band during the eyes-closed state.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FIB-4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC-IV database","authors":"Yu Pan, Yan-huo Xia, Xiao-hua Zhang, Xi-xi Cai, Jing-ye Pan, Yi-hua Dong","doi":"10.1111/adb.13361","DOIUrl":"https://doi.org/10.1111/adb.13361","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan–Meier curves were used to analyse the incidence of 28-day mortality among four groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192–1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239–1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178–1.490)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills
{"title":"Sex-specific negative affect-like behaviour and parabrachial nucleus activation induced by BNST stimulation in adult mice with adolescent alcohol history","authors":"Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills","doi":"10.1111/adb.13366","DOIUrl":"https://doi.org/10.1111/adb.13366","url":null,"abstract":"<p>Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute for stress exposure to increase the latency to consume a palatable food in a novel context (hyponeophagia) and promote social avoidance in adult mice with AIE history. Given the dense connections between the BNST and the parabrachial nucleus (PBN), a region involved in mediating threat assessment and feeding behaviours, we hypothesized that increased negative affect-like behaviours would be associated with PBN activation. Our results revealed that the chemogenetic stimulation of the dorsolateral BNST induced hyponeophagia in females with AIE history, but not in female controls or males of either group. Social interaction remained unaffected in both sexes. Notably, this behavioural phenotype was associated with higher activation of calcitonin gene-related peptide and dynorphin cells in the PBN. These findings provide new insights into the neurobiological mechanisms underlying the development of negative affect in females and highlight the potential involvement of the BNST-PBN circuitry in regulating emotional responses to alcohol-related stimuli.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alex H. Robinson, Justin Mahlberg, Trevor T.-J. Chong, Antonio Verdejo-Garcia
{"title":"Model-based and model-free mechanisms in methamphetamine use disorder","authors":"Alex H. Robinson, Justin Mahlberg, Trevor T.-J. Chong, Antonio Verdejo-Garcia","doi":"10.1111/adb.13356","DOIUrl":"10.1111/adb.13356","url":null,"abstract":"<p>People with methamphetamine use disorder (MUD) struggle to shift their behaviour from methamphetamine-orientated habits to goal-oriented choices. The model-based/model-free framework is well suited to understand this difficulty by unpacking the computational mechanisms that support experienced-based (model-free) and goal-directed (model-based) choices. We aimed to examine whether 1) participants with MUD differed from controls on behavioural proxies and/or computational mechanisms of model-based/model-free choices; 2) model-based/model-free decision-making correlated with MUD symptoms; and 3) model-based/model-free deficits improved over six weeks in the group with MUD. Participants with MUD and controls with similar age, IQ and socioeconomic status completed the Two-Step Task at treatment commencement (MUD <i>n</i> = 30, Controls <i>n</i> = 31) and six weeks later (MUD <i>n</i> = 23, Controls <i>n</i> = 26). We examined behavioural proxies of model-based/model-free decisions using mixed logistic regression, and their underlying mechanisms using computational modelling. At a behavioural level, participants with MUD were more likely to switch their choices following rewarded actions, although this pattern improved at follow up. At a computational level, groups were similar in their use of model-based mechanisms, but participants with MUD were less likely to apply model-free mechanisms and less likely to repeat rewarded actions. We did not find evidence that individual differences in model-based or model-free parameters were associated with greater severity of methamphetamine dependence, nor did we find that group differences in computational parameters changed between baseline and follow-up assessment. Decision-making challenges in people with MUD are likely related to difficulties in pursuing choices previously associated with positive outcomes.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephanie G. Scala, Min Su Kang, Sylvia M. L. Cox, Pedro Rosa-Neto, Gassan Massarweh, Marco Leyton
{"title":"Mesocorticolimbic function in cocaine polydrug users: A multimodal study of drug cue reactivity and cognitive regulation","authors":"Stephanie G. Scala, Min Su Kang, Sylvia M. L. Cox, Pedro Rosa-Neto, Gassan Massarweh, Marco Leyton","doi":"10.1111/adb.13358","DOIUrl":"10.1111/adb.13358","url":null,"abstract":"<p>Addictions are thought to be fostered by the emergence of poorly regulated mesocorticolimbic responses to drug-related cues. The development and persistence of these responses might be promoted by altered glutamate transmission, including changes to type 5 metabotropic glutamate receptors (mGluR5s). Unknown, however, is when these changes arise and whether the mGluR5 and mesocorticolimbic alterations are related. To investigate, non-dependent cocaine polydrug users and cocaine-naïve healthy controls underwent a positron emission tomography scan (15 cocaine users and 14 healthy controls) with [<sup>11</sup>C]ABP688, and a functional magnetic resonance imaging scan (15/group) while watching videos depicting activities with and without cocaine use. For some drug videos, participants were instructed to use a cognitive strategy to lower craving. Both groups exhibited drug cue-induced mesocorticolimbic activations and these were larger in the cocaine polydrug users than healthy controls during the session's second half. During the cognitive regulation trials, the cocaine users' corticostriatal responses were reduced. [<sup>11</sup>C]ABP688 binding was unaltered in cocaine users, relative to healthy controls, but post hoc analyses found reductions in those with 75 or more lifetime cocaine use sessions. Finally, among cocaine users (<i>n</i> = 12), individual differences in prefrontal [<sup>11</sup>C]ABP688 binding were associated with midbrain and limbic region activations during the regulation trials. Together, these preliminary findings raise the possibility that (i) recreational polydrug cocaine users show biased brain processes towards cocaine-related cues and (ii) repeated cocaine use can lower cortical mGluR5 levels, diminishing the ability to regulate drug cue responses. These alterations might promote susceptibility to addiction and identify early intervention targets.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138819990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellie B. Decker Ramirez, Miranda E. Arnold, Jesse R. Schank
{"title":"Vicarious defeat stress induces increased alcohol consumption in female mice: Role of neurokinin-1 receptor and interleukin-6","authors":"Ellie B. Decker Ramirez, Miranda E. Arnold, Jesse R. Schank","doi":"10.1111/adb.13357","DOIUrl":"https://doi.org/10.1111/adb.13357","url":null,"abstract":"<p>There is a high frequency of comorbidity of alcohol use disorder (AUD) and depression in human populations. We have studied this relationship in our lab using the social defeat stress (SDS) model, which results in both depression-like behaviours and increased alcohol consumption in male mice. However, standard SDS procedures are difficult to use in female mice due to a lack of territorial aggression. In the experiments presented here, we used vicarious defeat stress (VDS) to assess social withdrawal and alcohol consumption in female C57BL6/J mice. We also assessed the expression of interleukin-6 (IL6), which is a proinflammatory cytokine that is associated with depression in humans and sensitivity to SDS in mice. In these experiments, C57BL/6 female mice underwent 10 days of VDS where they witnessed the physical defeat of a male conspecific by an aggressive CD1 mouse. After the end of VDS, mice were either given access to alcohol or sacrificed for the measurement of IL6 expression. We found that VDS increased alcohol consumption and IL6 expression in the frontal cortex and hippocampus. Given that the neurokinin-1 receptor (NK1R) can mediate both stress-induced alcohol consumption and IL6 expression, we tested the ability of NK1R antagonism to reduce VDS-induced alcohol consumption and found that this treatment reduced alcohol intake in both VDS-exposed mice and in unstressed controls. The observed increase in alcohol consumption suggests that VDS is a model that can be utilized to study stress-induced alcohol consumption in female mice, and that this is sensitive to NK1R antagonism.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly E. Dunn, Andrew S. Huhn, Patrick H. Finan, Ami Mange, Cecilia L. Bergeria, Brion S. Maher, Jill A. Rabinowitz, Eric C. Strain, Denis Antoine
{"title":"Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype–genotype assessment","authors":"Kelly E. Dunn, Andrew S. Huhn, Patrick H. Finan, Ami Mange, Cecilia L. Bergeria, Brion S. Maher, Jill A. Rabinowitz, Eric C. Strain, Denis Antoine","doi":"10.1111/adb.13355","DOIUrl":"https://doi.org/10.1111/adb.13355","url":null,"abstract":"<p>Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3–5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13355","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}