Olsson Yasmin, Hodzic Kenan, Wass Caroline, Lidö Helga, Stangl Bethany L, O'Connor Sean, Plawecki Martin H, Ramchandani Vijay A, Söderpalm Bo, Jerlhag Elisabet
Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.
Alcohol Clin Exp Res (Hoboken). 2023 Aug;47(8):1453-1466. doi: 10.1111/acer.15132. Epub 2023 Jun 26.
The free-access (FA) intravenous alcohol self-administration (IV-ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV-ASA paradigms are associated with self-reported alcohol intake using the timeline follow-back method (TLFB). To evaluate how FA IV-ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B-PEth), and TLFB and measures obtained during IV-ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut-brain peptides involved in AUD pathophysiology.
Thirty-eight participants completed a laboratory session in which they self-administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV-ASA and subjective alcohol effects were rated during the experiment.
The study sample comprised 24 SD and 14 participants with DSM-5 mild AUD. Although BrACs were not associated with B-PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD.
No associations between B-PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV-ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV-ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV-ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD.
自由获取（FA）静脉内酒精自我给药（IV-ASA）范式是一种可识别人类酒精消费调节因子的实验方法。此外，IV-ASA范式的结果测量与使用时间线追溯法（TLFB）自我报告的酒精摄入量相关。为了评估FA IV-ASA如何反映现实生活中的饮酒情况，我们研究了近期酒精摄入量的客观标志物——血液中的磷脂酰乙醇（B-PEth）与TLFB以及酒精使用障碍（AUD）个体和社交饮酒者（SD）在IV-ASA期间获得的测量值之间的关系。我们还探讨了这些测量值与AUD病理生理学中涉及的肠脑肽之间的关联。
38名参与者完成了一次实验室实验，他们在实验中静脉内自我给药酒精。安全限度为200mg%，主要结果是平均和峰值呼气酒精浓度（BrAC）。在IV-ASA之前采集血样，并在实验期间对主观酒精效应进行评分。
研究样本包括24名SD和14名患有DSM-5轻度AUD的参与者。尽管在整个样本或AUD亚组中，BrAC与B-PEth或TLFB均无关联，但在SD中BrAC与TLFB存在关联。在两个亚组中，BrAC均与酒精渴望相关，但时间不同。AUD参与者的总胃饥饿素水平高于SD。
在轻度AUD组、SD组或整个样本中，未观察到B-PEth水平与达到的BrAC之间存在关联。仅在SD中，FA IV-ASA反映近期饮酒的能力在TLFB方面得到证实，而在轻度AUD参与者的较小亚样本或整个样本中均无关联。有必要进行进一步研究，纳入更大的AUD样本。BrAC与对酒精的渴望之间的关联表明，IV-ASA方法可能有助于评估针对渴望的干预措施。这可以通过使用FA IV-ASA模型来评估已批准的AUD药物疗法对渴望的影响来进行探索。
