Development of Drinabant for Treatment of Acute Cannabinoid Overdose

用于治疗急性大麻素过量的 Drinabant 的开发

基本信息

批准号：
10910764
负责人：
Tracey Rogers
金额：
$ 130.03万
依托单位：
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10910764
关键词：
Acute Agonist Anxiety Auditory Hallucination Beverages Binding Brain CNR1 gene Cannabinoids Cannabis Chemicals Clinical Clinical Research Clinical Trials Consumption Data Development Dose Drug Kinetics Emergency Care Flowers Food Formulation Goals Hospitalization Hour Individual Inhalation Injectable Intramuscular Injections Investigational New Drug Application Lead Marijuana Medical emergency Nausea Oral Administration Overdose Paranoia Pharmacodynamics Plants Psychotropic Drugs Reporting Research Route Scientist Smoke Smoking Symptoms Tetrahydrocannabinol Therapeutic Toxicology Visual Hallucination absorption acute symptom antagonist cannabinoid administration cannabinoid receptor clinical material improved intravenous injection medical attention pre-clinical preclinical development receptor research clinical testing synthetic cannabinoid synthetic marijuana tool

项目摘要

Acute cannabinoid overdose (ACO) results from the consumption of large quantities of cannabinoid compounds. These include delta-9-tetrahydrocannabinol (THC), the naturally occurring psychoactive compound in Cannabis plants, as well as other synthetic cannabinoid (SC) compounds. Although SCs are chemically distinct from THC, THC and SCs elicit psychoactive effects through the binding and activation of cannabinoid (CB) receptors in the brain, principally the CB-1 receptor. Initially developed as research tools to study CB receptors, SCs are reported to be more potent and efficacious than THC at activating CB-1 receptors. A critical issue with edibles is that absorption of the THC/SC through the gut is delayed compared to smoking. The subsequent delay in the onset of a high leads some to overconsume these edibles. Because it can be difficult to gauge how much THC/SC is contained in an individual edible, this overconsumption can quickly result in an overdose. Symptoms of ACO have been reported to last anywhere from several hours to days, leading some individuals to require emergency medical attention or even hospitalization. Individuals using SCs are about 30 times more likely to require emergency medical care than for smoked marijuana. The therapeutic hypothesis is that a CB-1 antagonist can reverse the clinical manifestations of ACO by replacing the agonist (THC or SC) bound to CB-1 receptors. Prior clinical studies have demonstrated that oral administration of CB-1 antagonists (drinabant, surinabant) can block the pharmacodynamic effects of inhaled THC. Orally administered drinabant has a slow onset, making it impractical to administer in the acute overdose setting. To improve the pharmacokinetics, the lead collaborators have proposed a parenteral route of administration (intravenous or intramuscular injection) that would be more amenable to treating ACO in the emergency medical setting. BrIDGs scientists have initiated a preclinical development campaign to advance drinabant to clinical evaluation. Development of an injectable formulation and dose range finding toxicology studies are underway. Planned activities include toxicology studies needed to support an Investigational New Drug (IND) application.

急性大麻素过量（ACO）是由于消耗大量大麻素化合物而产生的。其中包括大麻植物中天然存在的精神活性化合物以及其他合成大麻素（SC）化合物的Delta-9-四氢大麻酚（THC）。尽管SC在化学上与THC不同，THC和SCS通过大脑中大麻素（CB）受体的结合和激活（主要是CB-1受体）引起了精神活性。据报道，最初是作为研究CB受体的研究工具开发的，与激活CB-1受体相比，SCs比THC更有效，更有效。食用的一个关键问题是，与吸烟相比，THC/SC通过肠道的吸收延迟。随后的高发延迟导致一些食物过度处理这些食物。因为很难衡量单个可食用的THC/SC包含多少THC/SC，因此这种过度消费会迅速导致过量服用。据报道，ACO的症状持续了几个小时到几天，导致一些人需要紧急医疗救治甚至住院。使用SC的个人需要紧急医疗服务的可能性是烟熏大麻的30倍。治疗性假设是，CB-1拮抗剂可以通过取代与CB-1受体结合的激动剂（THC或SC）来逆转ACO的临床表现。先前的临床研究表明，口服CB-1拮抗剂（Drinabant，Surinabant）可以阻止吸入THC的药效动力作用。口服Drinabant的发作缓慢，使得在急性过量设置中进行施用是不切实际的。为了改善药代动力学，首席合作者提出了肠胃外的行政途径（静脉注射或肌内注射），在紧急医疗环境中可以治疗ACO。 Bridgs的科学家发起了一项临床前发展运动，以将Drinabant推向临床评估。正在开发可注射的配方和剂量范围发现毒理学研究。计划的活动包括支持研究新药（IND）应用所需的毒理学研究。