Treatment for cannabis use disorder
大麻使用障碍的治疗
基本信息
- 批准号:10546566
- 负责人:
- 金额:$ 31.99万
- 依托单位:
- 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:
- 关键词:Adverse effectsAffectAgonistAmericanAnhedoniaAnimalsAnti-Obesity AgentsAreaAwardBehavioralBenignBrainCNR1 geneCNR2 geneCanis familiarisCannabinoidsCannabisCellsChemicalsClinical DataCognitive TherapyDevelopmentDoseEmergency department visitEmotionalEuropeFDA approvedFailureG-Protein-Coupled ReceptorsGenerationsGoalsHumanImmuneLeadLegal patentMarijuanaMaximum Tolerated DoseOralOrganOutcomePenetrationPeripheralPharmaceutical PreparationsPharmacotherapyPhasePhysiologicalPlasmaProductionPropertyRattusReceptor SignalingResearch DesignRewardsRodentRouteSelf StimulationSignal TransductionSmall Business Innovation Research GrantSubstance Use DisorderTetrahydrocannabinolTherapeuticToxic effectToxicokineticsToxicologyWithdrawaladdictionantagonistbasebehavioral studychemical synthesisclinical candidatecohortcravingdesigndrug discriminationdrug of abusedysphoriaexperienceimaging studyinnovationinterestlead candidatemarijuana legalizationmarijuana usemarijuana use disordernext generationnovelnovel therapeuticspreclinical studypsychologicreceptorrimonabantscale upsmall moleculesocialsynthetic cannabinoidwelfare
项目摘要
Abstract
Our goal is to develop an innovative pharmacotherapy for cannabis use disorder (CUD) that affects over 4 million
Americans. We propose to develop a novel second generation PARTIAL inverse agonist of the cannabinoid 1
receptor (CB1) that has a benign behavioral profile for CUD. Cannabinoids are the second most abused class of
drug in the world and there is no FDA approved medication for CUD -- making this an area of urgent need. The
psychoactive effects of cannabis and synthetic cannabinoids result from activation of central CB1 receptors.
Blocking the rewarding and craving properties of drugs of abuse is a well-validated and accepted strategy for
substance use disorders (SUD) without a strong adverse physical withdrawal component. Rimonabant is a potent
FULL inverse agonist of the CB1 receptor that was approved in Europe as an anti-obesity agent. Unfortunately,
rimonabant produced adverse dysphoric effects in ~6% of users -- effects likely due to sustained high brain
exposure and potent inverse agonism, which led to its eventual discontinuation. In human studies, rimonabant
was efficacious in treating many aspects of CUD. Artiam Bio is developing the next generation of CB1 antagonists
that are expected to have a superior adverse effect profile compared to rimonabant and previous clinical
candidates. Artiam Bio’s lead compound is an orally active, potent, and selective CB1 partial inverse agonist with
limited brain penetration. This compound is functionally as efficacious as rimonabant but produces no
dysphoria/anhedonia in rodent studies. Further development of this compound is proposed through three aims.
Through aim 1, ~500 g of the compound will be synthesized using an established chemical route leveraging upon
Artiam’s experience with a congener. Through aims 2 and 3, dose range finding toxicological studies will be
performed in two species and toxicokinetic parameters will be established. Successful completion of this phase 1
SBIR application will pave the way for GLP regulatory studies and other IND-enabling activities of Artiam’s lead
candidate for CUD.
抽象的
我们的目标是开发一种针对影响超过 400 万人的大麻使用障碍 (CUD) 的创新药物疗法
美国人。我们建议开发一种新型第二代大麻素 1 的部分反向激动剂
受体 (CB1) 对 CUD 具有良性行为特征。大麻素是第二大滥用类别
世界上尚无 FDA 批准的治疗 CUD 的药物,这使得该领域成为一个迫切需要的领域。这
大麻和合成大麻素的精神作用是由中枢 CB1 受体激活引起的。
阻止滥用药物的奖励和渴望特性是一种经过充分验证和接受的策略
物质使用障碍(SUD),不具有强烈的不良身体戒断成分。利莫那班是一种有效的
CB1 受体的完全反向激动剂,在欧洲被批准作为抗肥胖剂。很遗憾,
利莫那班对大约 6% 的使用者产生不良的烦躁反应——这种影响可能是由于持续的高脑力造成的
暴露和有效的反向激动作用,导致其最终停产。在人体研究中,利莫那班
在治疗 CUD 的许多方面都有效。 Artiam Bio 正在开发下一代 CB1 拮抗剂
与利莫那班和之前的临床研究相比,预计具有更好的不良反应
候选人。 Artiam Bio 的先导化合物是一种口服活性、强效、选择性 CB1 部分反向激动剂,具有
大脑渗透力有限。该化合物在功能上与利莫那班一样有效,但不产生
啮齿动物研究中的烦躁/快感缺失。该化合物的进一步开发提出了三个目标。
通过目标 1,将利用已建立的化学路线合成约 500 克化合物
阿蒂亚姆与同类的经历。通过目标 2 和 3,毒理学研究的剂量范围将
在两个物种中进行,并将确定毒代动力学参数。顺利完成第一阶段
SBIR 申请将为 Artiam 主导的 GLP 监管研究和其他 IND 支持活动铺平道路
CUD 候选人。
项目成果
期刊论文数量(0)
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HERBERT H SELTZMAN其他文献
HERBERT H SELTZMAN的其他文献
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{{ truncateString('HERBERT H SELTZMAN', 18)}}的其他基金
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
- 批准号:
2458453 - 财政年份:1996
- 资助金额:
$ 31.99万 - 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
- 批准号:
2123524 - 财政年份:1996
- 资助金额:
$ 31.99万 - 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
- 批准号:
2749124 - 财政年份:1996
- 资助金额:
$ 31.99万 - 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
- 批准号:
2616076 - 财政年份:1996
- 资助金额:
$ 31.99万 - 项目类别:
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