Opioid and cannabinoid interactions in pain and reward

阿片类药物和大麻素在疼痛和奖励中的相互作用

• 批准号: 10352482
• 负责人: ROBERT M CAUDLE
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10352482
• 关键词: Absence of pain sensation; Acute; Affect; Analgesics; Attenuated; Behavior assessment; Behavioral; Behavioral Assay; Biological Assay; Brain; Cannabidiol; Cannabinoids; Cannabis; Chronic; Clinical; Controlled Study; Dependence; Depressed mood; Foundations; Future; Goals; Individual; Maps; Neurosciences; Opioid; Opioid Analgesics; Opioid Receptor; Oxycodone; Pain; Pain Clinics; Pain Measurement; Pain management; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Property; Psychological reinforcement; Public Health; Research; Rewards; Self Administration; Societies; System; Tetrahydrocannabinol; Variant; base; cannabinoid receptor; chronic pain; cost; experimental study; heuristics; human subject; innovation; multidisciplinary; neuroimaging; novel; novel strategies; opioid epidemic; opioid sparing; opioid use; pain behavior; pain model; prescription opioid; programs; relating to nervous system; substance use

Abstract Chronic pain is a significant public health problem that costs society billions of dollars per year and causes great suffering in countless individuals. Opioid-based medications are among the most prescribed for various forms of chronic pain contributing to the current opioid epidemic. Recently, cannabis and cannabinoid compounds (e.g., 9-tetrahydrocannabinol (THC) and cannabidiol (CBD)) have been described as having pain-alleviating properties. While these cannabinoids, particularly the less psychoactive variant, CBD, may offer alternatives to opioid treatments for pain, few well-controlled studies demonstrate analgesic efficacy, especially for CBD. While it is still unclear if cannabinoids are good stand-alone options for treating pain, cannabinoids may act as useful opioid-sparing drugs, given the substantial overlap between opioid and cannabinoid receptors in reward- and pain-related pathways. Our proposed project will focus on a heuristic approach that incorporates fundamental pharmacology, novel operant behavioral assays of pain, and functional neuroimaging. The long-term goal of this research program is to establish novel approaches to treat chronic pain by maximizing analgesic efficacy and minimizing abuse liability. The objective of this proposal, which embodies the first step toward this long- term goal, is to determine how CBD modifies the effects of oxycodone (OXY), a commonly prescribed opioid analgesic, in the contexts of chronic pain and opioid self-administration. Our overarching hypothesis is that CBD and OXY will act synergistically to yield enhanced analgesic effects, and that CBD will attenuate the effects of pain on OXY self-administration. Two major specific aims will be investigated: (1) to determine how CBD interacts with OXY to reduce chronic operant pain behaviors; and (2) to determine the interacting effects of chronic pain, OXY self-administration, and CBD on analgesia, reinforcement, and dependence. We will assess the effects of preexisting pain on OXY self-administration, as well as the effects of preexisting OXY self- administration on pain. The latter goal is a particularly innovative aspect of this proposal. CBD-modulatory effects on pain and OXY self-administration will be evaluated under both conditions. Neuroimaging will be used across experiments to map and quantify changes in neural connectivity across reward and pain centers of the brain following the various drug treatments (CBD, OXY) and pain states (acute, chronic). Further, we will use clinically important and innovative pain-depressed behavioral assessments that accurately model pain in human subjects. The rationale for completing these studies is that by determining how CBD and OXY interact to affect pain and substance use, we will establish the necessary foundation for future efforts to develop effective analgesics with reduced abuse liability. We believe we are particularly well suited to undertake this project because we have a unified (and already collaborating) multidisciplinary team with complementary expertise in behavioral neuroscience, pharmacology, and neuroimaging.

抽象的 慢性疼痛是一个重大的公共卫生问题，每年使社会损失数十亿美元，并导致巨大 遭受无数个人的痛苦。基于阿片类药物的药物是各种形式的规定最多的药物之一 慢性疼痛导致当前的阿片类药物流行。最近，大麻和大麻素化合物（例如 9-四氢大麻酚（THC）和大麻二酚（CBD）已被描述为具有疼痛 - 静脉缺血 特性。尽管这些大麻素，尤其是较少的精神活性变体CBD可能会提供替代方案 阿片类药物治疗疼痛，很少有控制良好的研究表明镇痛效率，尤其是CBD。尽管 目前尚不清楚大麻素是否是治疗疼痛的良好独立选择，大麻素可能是有用的 鉴于阿片类药物的药物在奖励和 与疼痛有关的途径。我们拟议的项目将重点介绍一种启发式方法，该方法结合了基本 药理学，疼痛的新型操作行为测定和功能性神经影像学。长期目标 该研究计划是通过最大化镇痛效率来建立新的方法来治疗慢性疼痛 并最大程度地减少虐待责任。该提案的目的是朝着这一长期迈进的第一步 术语目标是确定CBD如何修饰羟考酮（Oxy）的作用，羟考酮（Oxy）是一种常规的阿片类药物 在慢性疼痛和阿片类药物自我管理的背景下，镇痛药。我们的总体假设是 CBD和OXY将协同起作用以产生增强的镇痛作用，并且CBD会衰减效果 氧气自我给药的疼痛。将研究两个主要的具体目标：（1）确定CBD的方式 与Oxy相互作用以减少慢性操作疼痛行为； （2）确定相互作用效果 在镇痛，增强和依赖性方面的慢性疼痛，氧气自我给药和CBD。我们将 评估先前疼痛对氧自我给药的影响，以及先前存在的氧气自我的影响 疼痛管理。后来的目标是该提案的一个特别创新的方面。 CBD调节效应 在两种情况下，都将评估疼痛和氧气自我给药。神经影像学会将在 实验绘制和量化大脑奖励和疼痛中心神经连通性的变化 遵循各种药物治疗（CBD，Oxy）和疼痛状态（急性，慢性）。此外，我们将在临床上使用 重要且创新的痛苦抑郁的行为评估，可以准确地模拟人类受试者的疼痛。 完成这些研究的理由是，通过确定CBD和Oxy如何相互作用以影响疼痛和 使用物质，我们将为将来的努力建立必要的基础，以开发有效的镇痛药 减少虐待责任。我们相信我们特别适合进行该项目，因为我们有一个 统一（并且已经合作）多学科团队具有完善的行为专业知识 神经科学，药理学和神经影像学。