Translating CBD Treatment for Heroin Addiction

将 CBD 治疗海洛因成瘾

基本信息

批准号：
10667485
负责人：
YASMIN L. HURD
金额：
$ 79.59万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10667485
关键词：
Acute Address Amygdaloid structure Animal Model Animals Anxiety Autopsy Behavior Brain Brain region Calcium Signaling Cannabidiol Cannabinoids Cannabis Caring Cells Cessation of life Chronic Clinical Clinical Research Corpus striatum structure Cues Development Disease Dorsal Dose Double-Blind Method Double-blind trial Effectiveness Epidemic Epigenetic Process Exposure to Female Fiber Foundations Functional Magnetic Resonance Imaging Glutamate Receptor Glutamates Heroin Heroin Dependence Human Impairment Incubated Individual Investigation Knowledge Magnetic Resonance Magnetic Resonance Spectroscopy Measures Mediating Medical Midbrain structure Modeling Molecular Monitor N-acetylaspartate Nature Neurobiology Neurons Nucleus Accumbens Opiate Addiction Opioid Opioid agonist Oral Outcome Patients Persons Pharmaceutical Preparations Phase Phenotype Photometry Pilot Projects Placebos Population Prefrontal Cortex Protons Randomized Rattus Recording of previous events Regulation Relapse Reporting Reproducibility of Results Research Project Grants Rest Rodent Rodent Model Scanning Science Self Administration Series Services Signal Transduction Study models Substance of Abuse Synaptic plasticity System Techniques Therapeutic Therapeutic Agents Time Translating Translational Research Treatment Failure Ventral Striatum abuse liability addiction craving drug abstinence drug craving drug seeking behavior effective therapy epigenome evidence base follow-up gene network heroin abuser heroin use human model human study human subject improved in vivo insight male neural neural circuit neuroimaging novel novel therapeutics opioid agonist therapy opioid epidemic opioid misuse opioid therapy opioid use opioid use disorder overdose death phase 1 study pre-clinical preclinical study relapse prevention response social stigma sociodemographic group substance use tool transcriptome translational goal translational study treatment strategy

项目摘要

The abuse and misuse of opioids has led to an epidemic of major proportions that has impacted all sociodemographic groups in the USA and led to an unfathomable number of deaths each year. Of the millions of people suffering today from an opioid use disorder, the normal treatments are opioid agonist medication therapies that have marked stigma and are subject to restrict governmental regulations that unfortunately have limited the number of people possible to treat. Moreover, although such opioid treatment strategies have improved substance use outcomes, they do not effectively treat opioid craving that might result in high rates of relapse. Using a strategy of indirectly regulating neural systems to modulate opioid-related behavior, our preclinical rodent studies had previously demonstrated that cannabidiol (CBD), a non-rewarding component of cannabis, specifically inhibited cue-induced heroin-seeking behavior. CBD's selective effect on drug-seeking behavior endured two or more weeks after the last drug administration following short-term CBD exposure. Intriguingly, these effects were replicated in a randomized double-blinded human study where abstinent heroin abusers reported reduced cue-induced drug craving (and anxiety) following acute CBD administration and the effects persisted even a week after the last administration of the CBD. The fact that drug craving is generally triggered by exposure to conditioned cues suggests that CBD might be an effective treatment for heroin craving and related behaviors that maintain the chronic relapsing nature of this disorder. CBD thus represents a strong candidate for the development as a potential therapeutic agent in humans for opioid craving and relapse prevention. However, the neurobiological effects of CBD are still unknown. It is the goal of this translational project to (1) Characterize the effects of CBD on neural connectivity and cue-induced neural activity within mesocorticolimbic brain circuits in abstinent heroin subjects using systems-level functional magnetic resonance imaging (fMRI), (2) Determine CBD effects on in vivo glutamatergic (and related neurometabolites) using Proton-Magnetic resonance spectroscopy (1H MRS) and (3) Elucidate glutamatergic and related synaptic plasticity mechanisms underlying the effects of CBD on heroin seeking behavior in translational rodent models using MRS, in vivo photometry (neural activity) and molecular and epigenetic sequencing of discrete brain regions. Altogether, knowledge obtained from this unique translational study will advance fundamental understanding of the neurobiology underlying phenotypes that drive addiction and provide science-based evidence towards the development of CBD as a new therapeutic tool to help address the opioid crisis.

阿片类药物的滥用和滥用导致了主要比例的流行，这影响了所有人美国的社会人口统计学群体，每年导致许多死亡人数。数百万当今患有阿片类药物使用障碍的患者，正常治疗是阿片类药物药物标志着污名并受到限制政府法规的治疗，不幸的是限制可能治疗的人数。而且，尽管这种阿片类药物治疗策略已经改善物质使用结果，它们没有有效地治疗阿片类药物的渴望，这可能会导致高率复发。使用间接调节神经系统来调节阿片类药物相关的行为的策略临床前啮齿动物研究以前已经证明了大麻二酚（CBD），这是一种非奖励成分大麻，特别抑制了提示引起的海洛因寻求行为。 CBD对寻求毒品的选择性影响短期CBD暴露后，在上一次药物管理后两周后，行为忍受了两周或更多星期。有趣的是，这些效果在戒除海洛因的随机双盲人类研究中得到了复制施虐者报告说，急性CBD给药后提示诱导的药物渴望（和焦虑）和 CBD最后一次管理后一周，效果仍然存在。渴望毒品的事实通常是通过暴露于条件提示的触发，表明CBD可能是海洛因的有效治疗方法保持这种疾病的慢性复发性质的渴望和相关行为。 CBD因此表示作为人类潜在治疗剂的发展，是阿片类药物渴望和预防复发。但是，CBD的神经生物学效应仍然未知。这是目标的目标转化项目（1）表征CBD对神经连通性和提示诱导的神经的影响使用系统级功能的戒律的海洛因受试者中的中质粒脑电路中的活动磁共振成像（fMRI），（2）确定CBD对体内谷氨酸能的影响（及相关使用质子 - 磁共振光谱（1H MRS）和（3）阐明谷氨酸能的神经代谢物）以及CBD对海洛因寻求行为的影响的相关突触可塑性机制使用MRS，体内光度法（神经活性）以及分子和表观遗传学的翻译啮齿动物模型离散大脑区域的测序。从这项独特的翻译研究中获得的知识总共将对推动成瘾和成瘾和提供基于科学的证据以开发CBD作为一种新的治疗工具，以帮助解决阿片类药物危机。