Endocannabinoid System Alterations in Opioid Use Disorder (OUD)

阿片类药物使用障碍 (OUD) 中的内源性大麻素系统改变

基本信息

批准号：
10303918
负责人：
Anahita Bassir Nia
金额：
$ 20.94万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10303918
关键词：
2-arachidonylglycerol Age Agonist Animal Model Animals Attention Attenuated Blood Blood specimen Brain imaging Brain region CNR1 gene Cannabinoids Cerebral cortex Chronic Clinical Research Clinical Trials Collaborations DSM-V Data Development Diagnosis Dopamine Dose Down-Regulation Drug usage Endocannabinoids Enhancers Enzymes Ethnic Origin Exposure to FAAH inhibitor Feasibility Studies Gender Goals Hippocampus (Brain)Human Individual Ligands Literature Measurement Measures Methadone Methods Midbrain structure Monitor Monoacylglycerol Lipases Neurons Nicotine Nucleus Accumbens Opiate Addiction Opioid Peripheral Pharmaceutical Preparations Pharmacology Plasma Positron-Emission Tomography Psychoses Race Reporting Research Resolution Rewards Sampling Serum System Therapeutic Time Universities Up-Regulation Withdrawal Symptom anandamide endogenous cannabinoid system endogenous opioids fatty acid amide hydrolase imaging study in vivo interest liquid chromatography mass spectrometry marijuana use disorder methadone treatment mu opioid receptors mu receptors novel novel strategies opioid epidemic opioid use opioid use disorder opioid withdrawal pre-clinical receptor expression repository tomography

项目摘要

ABSTRACT There are close interactions between the endogenous opioid system and endocannabinoid (eCB) system, which result in stronger reinforcing/rewarding effects of both opioids and cannabinoids. Targeting the eCB system has attracted great attention in the treatment of opioid use disorder (OUD), particularly given the urgent need to curb the current opioid crisis in the US. Increasing lines of evidence from animal studies demonstrate that chronic opioid use suppresses the eCB system. In particular, animal studies of chronic opioid administration reported decreased cannabinoid receptor type 1 (CB1R) in cortex. However, CB1R availability has not yet been investigated in humans with OUD. The availability of a PET ligand for CB1R makes it possible to study CB1R availability in individuals with OUD in vivo for the first time. The aim of this proposal is to use the CB1R-specific ligand [11C]OMAR and High Resolution Research Tomography (HRRT), a PET scanner with the highest sensitivity and resolution available for human brain imaging, to measure CB1R availability in vivo in individuals with OUD. As an exploratory aim, we will also measure peripheral levels of the eCBs anandamide (AEA) and 2-arachidonoylglycerol (2-AG) using liquid chromatography–mass spectrometry (LC-MS). Methods: Otherwise healthy individuals with opioid use disorder (on stable dose of maintenance methadone) and age-, gender-, race/ethnicity-matched healthy controls without recent use of any drugs (except nicotine, which will be matched between two groups) will undergo a single PET scan with [11C]OMAR and blood sampling to measure serum eCB levels (AEA and 2-AG). Hypotheses: Consistent with animal studies, relative to healthy controls, individuals with OUD will have lower availability of CB1R in cerebral cortex. Pilot data: Individuals with OUD (n=2) showed 12.76% lower cortical CB1R availability compared to matched historical controls from our repository of [11C]OMAR PET studies.

抽象的内源性阿片系统和内源性大麻素（eCB）系统之间存在密切的相互作用，这导致阿片类药物和大麻素针对 eCB 产生更强的强化/奖励作用。系统在阿片类药物使用障碍（OUD）的治疗中引起了高度关注，特别是考虑到紧急情况越来越多的动物研究证据表明，需要遏制美国当前的阿片类药物危机。长期使用阿片类药物会抑制 eCB 系统，特别是慢性阿片类药物的动物研究。管理报告减少了皮质中的 1 型大麻素受体 (CB1R)，但是 CB1R 的可用性。尚未在患有 OUD 的人类中进行研究，CB1R 的 PET 配体的可用性使其成为可能。首次研究 CB1R 在 OUD 个体体内的可用性。该提案的目的是使用 CB1R 特异性配体 [11C]OMAR 和高分辨率研究断层扫描 (HRRT)，一种具有人类大脑最高灵敏度和分辨率的 PET 扫描仪成像，以测量 OUD 个体体内 CB1R 的可用性作为探索性目标，我们还将。使用液体测量 eCBs anandamide (AEA) 和 2-arachidonoylglycerol (2-AG) 的外周水平色谱-质谱（LC-MS）。方法：患有阿片类药物使用障碍的其他健康个体（使用稳定剂量的维持美沙酮）以及年龄、性别、种族/民族匹配的健康对照，近期未使用任何药物（尼古丁除外，将在两组之间进行匹配）将接受使用 [11C]OMAR 和血液的单次 PET 扫描取样测量血清 eCB 水平（AEA 和 2-AG）。假设：与动物研究一致，相对于健康对照，患有 OUD 的个体的大脑皮层中 CB1R 的可用性。试点数据：与匹配的个体相比，具有 OUD 的个体 (n=2) 的皮质 CB1R 可用性降低 12.76% 来自我们的 [11C]OMAR PET 研究存储库的历史对照。