Todaro Dustin R, Volkow Nora D, Langleben Daniel D, Shi Zhenhao, Wiers Corinde E
Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Neurosci Insights. 2024 Apr 24;19:26331055241247156. doi: 10.1177/26331055241247156. eCollection 2024.
Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients.
非致命性阿片类药物过量与显著的发病率相关。阿片类药物引起的呼吸抑制导致的缺氧性脑损伤是这种发病率的关键机制。例如，报告描述了阿片类药物使用者中与海马体急性损伤相关的遗忘综合征，海马体是一个极易受到缺氧性损伤的脑区。在我们最近的研究中，我们调查了非致命性阿片类药物过量对有过量用药史（OD）的阿片类药物使用障碍（OUD）患者海马体体积的影响，并与无既往过量用药史（NOD）的患者进行了比较。使用结构磁共振成像（MRI）和基于体素的形态测量法，我们观察到有OD史的患者海马体体积低于NOD组。这些发现支持了非致命性阿片类药物过量与海马体损伤之间的关联，我们推测这导致了最近报道的与OUD相关的遗忘综合征病例。在这里，我们回顾我们的研究结果以及非致命性阿片类药物过量中急性和延迟性海马体损伤潜在的病理生理机制。我们还讨论了非法阿片类药物供应中芬太尼和赛拉嗪污染增加对过量用药风险和脑损伤的影响。最后，我们强调了对OUD患者中未得到充分重视的神经损伤和认知功能障碍进行临床管理的注意事项。
