Reducing the deleterious effects of synthetic cannabinoid withdrawal on emotionality and motivation
减少合成大麻素戒断对情绪和动机的有害影响
基本信息
- 批准号:10134039
- 负责人:
- 金额:$ 6.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The use of synthetic cannabinoid receptor agonists, first developed as research tools and
later sprayed on plant material and sold as a legal alternative to cannabis, has increased in recent
years, despite attempts to limit their commercial availability. This is due at least in part to the
common perception of cannabinoids as a "soft drugs" with relatively mild withdrawal symptoms.
However, a growing literature indicates Cannabis Use Disorder affects many users, the primary
symptoms being emotional (e.g., anxiety, depression, agitation), somatic (e.g., gastric upset, sleep
disturbance), and cognitive (e.g., cravings for cannabis). Not surprisingly, alleviating the aversive
symptoms brought about by abstinence is common cause of relapse. Thus, there is a need to
develop new treatments for cannabinoid dependence.
Current preclinical research on cannabis dependence uses somatic outcomes to quantify
cannabis withdrawal. These models have been useful but do not explore the emotional aspects of
cannabinoids withdrawal that are most salient in humans and contribute directly to relapse. Our
preliminary data indicate that withdrawal from the phytocannabinoid Δ9-tetrahydrocannabinol (THC),
or the synthetic cannabinoid JWH-018, significantly decreases marble burying, a proxy measure of
agitation, and increases struggling in the tail suspension test. The goal of Aim 1 is to fully
characterize the behavioral effects of synthetic cannabinoid withdrawal on preclinical measures of
emotionality and motivation. We will treat mice repeatedly with the prototypical synthetic cannabinoid
agonist JWH-018 or CP55,940 and induce precipitated and spontaneous withdrawal, to quantify
withdrawal behaviors in a battery of tests to model emotion, motivation, and somatic signs of
withdrawal.
In addition to behavioral interventions, adjuvant therapies have been used with much
success to reduce drug dependence. The goal of Aim 2 of the proposed studies is to normalize
JWH-018 withdrawal-induced behavioral changes by positive allosteric modulation of the CB1
receptor. We propose to administer a positive and a negative allosteric modulator to mice
undergoing withdrawal, and to test alterations in behavioral assays that our unpublished preliminary
data indicate are altered by cannabinoid withdrawal. It is expected that positive allosteric modulation
will attenuate JWH-018 withdrawal-induced behavioral changes. The successful completion of the
proposed project will yield preliminary data for larger scale neurobehavioral project, with the goal of
informing human cannabinoid dependence research.
合成大麻素受体激动剂的使用首先是作为研究工具开发的,
后来喷洒在植物材料上,作为大麻的法律的替代品出售,
多年来,尽管试图限制其商业可用性。这至少部分是由于
大麻素是一种“软性毒品”,戒断症状相对较轻。
然而,越来越多的文献表明,大麻使用障碍影响许多用户,主要是
情绪化症状(例如,焦虑、抑郁、激动),躯体(例如,胃部不适,睡眠
干扰),和认知(例如,对大麻的渴望)。毫不奇怪,减轻厌恶
戒断带来的症状是复吸的常见原因。因此,有必要
开发大麻素依赖的新疗法。
目前对大麻依赖的临床前研究使用躯体结果来量化
大麻戒断这些模型是有用的,但没有探讨情感方面的问题。
大麻素戒断在人类中最突出,并直接导致复发。我们
初步数据表明,从植物大麻素Δ9-四氢大麻酚(THC)中戒断,
或合成大麻素JWH-018,显着减少大理石埋葬,一个代理措施,
搅拌,并在尾部悬挂试验中增加挣扎。目标1的目标是充分
表征合成大麻素戒断对临床前测量的行为影响,
情绪和动机。我们将用典型的合成大麻素反复治疗老鼠
激动剂JWH-018或CP 55,940,并诱导沉淀和自发戒断,以定量
在一系列测试中的退缩行为,以模拟情绪,动机和
戒断
除了行为干预外,辅助治疗也被用于许多
成功减少药物依赖。拟议研究的目标2是标准化
JWH-018通过CB 1的正向别构调节引起戒断行为变化
受体的我们建议给小鼠施用正变构调节剂和负变构调节剂
经历戒断,并测试行为测定的变化,我们未发表的初步
数据显示,大麻素戒断会改变。预期正变构调节
会减弱JWH-018戒断引起的行为变化圆满完成
拟议的项目将为更大规模的神经行为项目提供初步数据,目标是
为人类大麻素依赖研究提供信息。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice.
短效合成大麻素 AB-FUBINACA 会诱导小鼠产生身体依赖性。
- DOI:10.1016/j.drugalcdep.2020.108179
- 发表时间:2020
- 期刊:
- 影响因子:4.2
- 作者:Trexler,KristenR;Vanegas,SOlivia;Poklis,JustinL;Kinsey,StevenG
- 通讯作者:Kinsey,StevenG
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Steven G. Kinsey其他文献
#74 Steroid resistance and anxiety-like behaviors develop in aged, socially defeated CD-1 mice
- DOI:
10.1016/j.bbi.2005.10.080 - 发表时间:
2005-07-01 - 期刊:
- 影响因子:
- 作者:
Steven G. Kinsey;Michael T. Bailey;John F. Sheridan;David A. Padgett - 通讯作者:
David A. Padgett
Targeting Fatty Acid Amide Hydrolase (FAAH) to Treat Pain and Inflammation
- DOI:
10.1208/s12248-008-9075-y - 发表时间:
2009-01-29 - 期刊:
- 影响因子:3.700
- 作者:
Joel E. Schlosburg;Steven G. Kinsey;Aron H. Lichtman - 通讯作者:
Aron H. Lichtman
The synthetic cannabinoid agonist WIN 55,212-2 reduces experimental pruritus via CB<sub>2</sub> receptor activation
- DOI:
10.1016/j.neuropharm.2024.110216 - 发表时间:
2025-02-15 - 期刊:
- 影响因子:
- 作者:
Antonio Matt Reck;David P. Siderovski;Steven G. Kinsey - 通讯作者:
Steven G. Kinsey
Steven G. Kinsey的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Steven G. Kinsey', 18)}}的其他基金
Stemming the opioid-induced pain cascade via cannabinoid modulation
通过大麻素调节阻止阿片类药物引起的疼痛级联反应
- 批准号:
10218325 - 财政年份:2021
- 资助金额:
$ 6.58万 - 项目类别:
Stemming the opioid-induced pain cascade via cannabinoid modulation
通过大麻素调节阻止阿片类药物引起的疼痛级联反应
- 批准号:
10435486 - 财政年份:2021
- 资助金额:
$ 6.58万 - 项目类别:
Endocannabinoid modulation of affective signs of cannabinoid withdrawal
内源性大麻素对大麻素戒断情感体征的调节
- 批准号:
8806670 - 财政年份:2015
- 资助金额:
$ 6.58万 - 项目类别:
Targeting multiple enzyme systems to reduce arthritic pain and inflammation
针对多种酶系统来减轻关节炎疼痛和炎症
- 批准号:
8878443 - 财政年份:2015
- 资助金额:
$ 6.58万 - 项目类别:
相似海外基金
Brain-invading monocytes promote the deleterious consequences of status epilepticus
侵入大脑的单核细胞会促进癫痫持续状态的有害后果
- 批准号:
10062530 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10400036 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10615675 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10153794 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Brain-invading monocytes promote the deleterious consequences of status epilepticus
侵入大脑的单核细胞会促进癫痫持续状态的有害后果
- 批准号:
10303046 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Brain-invading monocytes promote the deleterious consequences of status epilepticus
侵入大脑的单核细胞会促进癫痫持续状态的有害后果
- 批准号:
9913177 - 财政年份:2019
- 资助金额:
$ 6.58万 - 项目类别:
Deleterious effects of fetal alcohol exposure on brain development in monkeys
胎儿酒精暴露对猴子大脑发育的有害影响
- 批准号:
502670-2017 - 财政年份:2018
- 资助金额:
$ 6.58万 - 项目类别:
Postdoctoral Fellowships
Maternal consumption of freeze-dried grape powder in pregnancy to mitigate the deleterious effects of perinatal iron deficiency on fetal development.
母亲在怀孕期间食用冻干葡萄粉可以减轻围产期缺铁对胎儿发育的有害影响。
- 批准号:
411258 - 财政年份:2018
- 资助金额:
$ 6.58万 - 项目类别:
Studentship Programs
Deleterious effects of fetal alcohol exposure on brain development in monkeys
胎儿酒精暴露对猴子大脑发育的有害影响
- 批准号:
502670-2017 - 财政年份:2017
- 资助金额:
$ 6.58万 - 项目类别:
Postdoctoral Fellowships
Defining the Deleterious Effects of Environmental Pollutants at a Mechanistic Level
从机制层面定义环境污染物的有害影响
- 批准号:
MR/R009848/1 - 财政年份:2017
- 资助金额:
$ 6.58万 - 项目类别:
Research Grant