Cannabidiol Pharmacotherapy for Comorbid Opioid Addiction and Chronic Pain

大麻二酚药物治疗阿片类药物成瘾和慢性疼痛

基本信息

批准号：
10605357
负责人：
Joao Paulo De Aquino
金额：
$ 19.17万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10605357
关键词：
Acceleration Acute Adverse effects Adverse event Analgesics Animals Behavior Behavioral Paradigm Biological Markers Biometry Board Certification Brief Pain Inventory Cannabidiol Cannabinoids Clinical Clinical Trials Collaborations Connecticut Cue-induced relapse Cues DSM-V Data Development Dose Enrollment Foundations Goals Grant Heroin Hour Human Institution Laboratory Study Link Maintenance Measures Mentored Patient-Oriented Research Career Development Award Mentors Methadone Methods Morbidity - disease rate National Institute of Drug Abuse Opiate Addiction Opioid Opioid agonist Oral Outcome Outcome Study Pain Pain Measurement Pain Research Pain management Participant Patient Self-Report Patients Persons Pharmaceutical Preparations Pharmacotherapy Placebo Control Placebos Population Positioning Attribute Property Psychiatrist Questionnaires Randomized Relapse Research Research Training Resources Safety Self Administration Sensory Severities Sex Differences Techniques Testing Therapeutic Time Training Treatment Efficacy Urine Verbal Learning Visual Vulnerable Populations Work Writing abuse liability addiction antinociception behavioral pharmacology career chronic pain clinical training cognitive testing comorbidity computerized craving drug testing endogenous cannabinoid system hedonic indexing meetings mortality multimodality new therapeutic target non-cancer chronic pain novel novel therapeutics opioid agonist therapy opioid treatment program opioid use opioid use disorder overdose death pain reduction pain sensitivity patient population performance tests preclinical study programs response responsible research conduct safety assessment safety study skills symposium therapeutic biomarker treatment response

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal seeks to investigate the analgesic and anti-craving efficacy of Cannabidiol (CBD) for comorbid opioid use disorder (OUD) and chronic pain. Chronic pain afflicts approximately 70% of people with OUD. Opioid agonist treatment effectively reduces opioid use overdose deaths, but does not alleviate chronic pain. Convergent preclinical studies have shown that cannabinoids reduce pain sensitivity and opioid-seeking behavior, suggesting they could be leveraged for treatment. Yet, the therapeutic efficacy of cannabinoids for comorbid OUD and chronic pain remains unknown. Given CBD’s lack of hedonic properties and established analgesic and anti-craving effects, it holds particular therapeutic promise for this population. Quantitative Sensory Testing (QST) is a computerized pain assessment method used to reliably measure antinociception and predict the pain treatment response. QST pain biomarkers can be integrated with behavioral paradigms to investigate the two-pronged efficacy of CBD for alleviating pain sensitivity and cue- induced opioid craving. The objective of this proposal is to apply behavioral pharmacology, multimodal pain research and clinical trial methods to study the safety and therapeutic efficacy of CBD for people with comorbid OUD and chronic pain. This will have a significant impact for this patient population, by (i) determining the safety of acute CBD administration (Aim 1); (ii) determining the dose of CBD required to reduce pain sensitivity and cue-induced opioid craving (Aim 2); (iii) understanding the safety of long-term CBD co-administration with opioid agonist maintenance (Aim 3), and (iv) providing preliminary data on the efficacy of CBD to reduce pain severity/interference and opioid craving in the clinical setting (Aim 4). Aims 1 and 2 will be carried out through human laboratory study, and Aims 3 and 4 will be executed through a pilot clinical trial. These studies will serve as the basis for novel treatments and therapeutic biomarkers for comorbid OUD and chronic pain. This proposal will integrate state-of-the-art facilities at Yale and at the VA Connecticut, with established collaborations with local opioid treatment programs. The applicant has assembled a renowned team of expert mentors in the fields of opioid, cannabinoid and pain research. This proposal builds on preliminary work on cannabinoid modulation of pain sensitivity in humans with comorbid OUD and chronic pain. Formal didactics, symposia and national scientific meetings will support the applicant’s training. Specific training goals include developing exceptional skills in (i) behavioral pharmacology of addiction (ii) multimodal assessment of pain, (iii) clinical trials and advanced biostatistics, (iv) grant writing, and (v) responsible conduct of research. Finally, this application leverages the applicant’s robust clinical foundation as a board-certified addiction psychiatrist. The vital support from this K23 award will allow the applicant’s scientific development, leading to an independent research program that timely combines interdisciplinary methods towards developing novel therapeutics for OUD and chronic pain.

项目概要/摘要该提案旨在研究大麻二酚 (CBD) 的镇痛和抗渴功效约 70% 的患者患有阿片类药物使用障碍 (OUD) 和慢性疼痛。 OUD。阿片类药物激动剂治疗可有效减少阿片类药物使用过量死亡，但不能缓解慢性病。临床前研究表明，大麻素可降低疼痛敏感性和阿片类药物寻求。行为，表明它们可以用于治疗然而，大麻素的治疗功效。鉴于 CBD 缺乏享乐特性且已确定， OUD 和慢性疼痛的共病仍然未知。由于具有镇痛和抗渴求作用，它对这一人群具有特殊的治疗前景。定量感官测试 (QST) 是一种计算机化疼痛评估方法，用于可靠地可以将 QST 疼痛生物标志物与测量预期感受并预测疼痛治疗反应相结合。行为范式研究 CBD 对缓解疼痛敏感性和提示的双管齐下功效该提案的目的是应用行为药理学、多模式疼痛。研究 CBD 对合并症患者的安全性和治疗效果的研究和临床试验方法通过 (i) 确定 OUD 和慢性疼痛，这将对这一患者群体产生重大影响。急性 CBD 给药的安全性（目标 1）；（ii）确定降低疼痛敏感性所需的 CBD 剂量和线索诱发的阿片类药物渴望（目标 2）；（iii）了解长期 CBD 联合用药的安全性；阿片类激动剂维持治疗（目标 3），以及 (iv) 提供有关 CBD 减轻疼痛功效的初步数据临床环境中的严重性/干扰和阿片类药物渴望（目标 1 和 2）将通过以下方式实现。人类实验室研究，目标 3 和 4 将通过试点临床试验来执行。作为 OUD 共病和慢性疼痛的新疗法和治疗生物标志物的基础。该提案将整合耶鲁大学和康涅狄格州退伍军人管理局的最先进设施，并建立与当地阿片类药物治疗项目合作。申请人组建了一支著名的专家团队。该提案建立在阿片类药物、大麻素和疼痛研究领域的初步工作的基础上。大麻素对患有 OUD 和慢性疼痛的人类疼痛敏感性的调节。研讨会和国家科学会议将支持申请人的培训，具体培训目标包括：培养以下方面的特殊技能：(i) 成瘾的行为药理学 (ii) 疼痛的多模式评估，(iii) 临床试验和高级生物统计学，（iv）资助写作，以及（v）负责任的研究行为最后，这。申请利用申请人强大的临床基础作为委员会认证的成瘾症状。 K23 奖项的重要支持将使申请人的科学发展成为独立的及时结合跨学科方法来开发新疗法的研究计划 OUD 和慢性疼痛。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies.

大麻和 delta-9-四氢大麻酚缓解阿片类药物戒断：观察性和实验性人体研究的系统回顾。

DOI：
发表时间：
2022-12-01
期刊：
影响因子：
4.2
作者：
De Aquino, Joao P;Bahji, Anees;Gómez, Oscar;Sofuoglu, Mehmet
通讯作者：
Sofuoglu, Mehmet

Buprenorphine Treatment of Fentanyl-Related Opioid Use Disorder.

丁丙诺啡治疗芬太尼相关的阿片类药物使用障碍。

DOI：
发表时间：
2022-04-26
期刊：
影响因子：
0
作者：
Jegede, Oluwole;Parida, Suprit;De Aquino, Joao P
通讯作者：
De Aquino, Joao P

From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder.

从禁忌到治疗：迷幻药在治疗疼痛和阿片类药物使用障碍中的出现。

DOI：
发表时间：
2024-04-16
期刊：
影响因子：
3.4
作者：
Weleff, Jeremy;Nunes, Julio C;Costa, Gabriel P A;Sofuoglu, Mehmet;MacLean, R Ross;De Aquino, Joao P
通讯作者：
De Aquino, Joao P

Impact of delivery rate on the acute response to intravenous nicotine: A human laboratory study with implications for regulatory science.

输送率对静脉注射尼古丁急性反应的影响：一项对监管科学具有影响的人体实验室研究。

DOI：
发表时间：
2022-03
期刊：
影响因子：
3.4
作者：
De Aquino, Joao P;MacLean, R Ross;Gueorguieva, Ralitza;DeVito, Elise E;Eid, Tore;Sofuoglu, Mehmet
通讯作者：
Sofuoglu, Mehmet

Brief report: The influence of childhood trauma on the effects of delta-9-tetrahydrocannabinol in persons with opioid use disorder.

简要报告：童年创伤对 delta-9-四氢大麻酚对阿片类药物使用障碍患者的影响的影响。

DOI：
发表时间：
2024-05
期刊：
影响因子：
0
作者：
Rogan, Michael;Nunes, Julio C;Xie, Catherine Z;Sofuoglu, Mehmet;Pittman, Brian;De Aquino, Joao P
通讯作者：
De Aquino, Joao P