Bath Salts: abuse-related and toxic effects

浴盐：滥用相关和毒性作用

基本信息

批准号：
10162572
负责人：
Gregory Thomas Collins
金额：
$ 35.92万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10162572
关键词：
Acute Adolescence Adolescent Adult Adverse reactions Affect Aggressive behavior Animal Model Blood Pressure Caffeine Canis familiaris Cardiopulmonary Cardiovascular system Cessation of life Cocaine Complex Designer Drugs Development Diarrhea Dose Drug Interactions Drug usage Effectiveness Emergency department visit Epidemic Female Female Adolescents Fentanyl Floods Future Heart Rate Heroin High School Student Hypertension Incidence Individual Knowledge Laboratories Life Life Experience Link Literature Male Adolescents Methamphetamine Modeling Monitor Naloxone Nature Opiate Addiction Opioid Overdose Patient Self-Report Pattern Pharmaceutical Preparations Pharmacology Procedures Public Health Radio Rattus Recording of previous events Recreational Drugs Reporting Research Project Grants Respiration Savings Self Administration Students Tachycardia Telemetry Testing Time Toxic effect United States Violence Withdrawal Work analog base bath salts cathinone drug market drug of abuse effective therapy epidemiologic data improved innovation male novel opioid abuse opioid injection opioid mortality opioid overdose opioid user opioid withdrawal overdose death polysubstance abuse polysubstance use prescription opioid recreational drug use reinforcer stimulant use synthetic drug synthetic opioid trend vocalization

项目摘要

PROJECT SUMMARY/ABSTRACT “Designer drugs” burst onto the United States (US) recreational drug market in early 2009. By 2011, “bath salts,” which are most often mixtures of synthetic cathinones and other drugs such as caffeine, were linked to numerous press reports of bizarre and violent behavior, and accounted for well over 20,000 emergency room visits. Over the nearly 10 years since their introduction, the number of synthetic cathinones available for use has grown from 3 (MDPV, methylone, and mephedrone) to over 140. Based on work from our lab and others, we now know that the reinforcing effects of cathinones exist on a continuum, with drugs such as methylone functioning as relatively modest reinforcers (cocaine>methylone), and drugs such as MDPV, and α-PVP functioning as exceptionally powerful reinforcers capable of maintaining significantly greater levels of responding than either cocaine or methamphetamine. In addition evidence to show that the reinforcing effectiveness of cocaine and synthetic cathinones, such as MDPV and α-PVP, is directly related to their selectivity for DAT over SERT, our laboratory has also shown that these reinforcing (and toxic) effects can be synergistically enhanced when drugs such as MDPV and methylone are administered in combination with other “bath salts” constituents, such as caffeine. In the last 5 years, we have learned a great deal about the pharmacology and abuse-related effects of synthetic cathinones; however, over this same time the synthetic drug market and the landscape of recreational drug use more broadly have changed dramatically. In 2013, heroin began to supplant prescription opioids as opioid users’ drug of choice; by 2014, synthetic opioids, mainly fentanyl, had flooded the market. These changes coincided with a doubling of the incidence of opioid-related deaths, from ~25,000 in 2013 to >47,000 in 2017, over half of which (~28,000) were linked to synthetic opioids, such as fentanyl. Over this same time, overdose deaths related to stimulants (e.g., cocaine, methamphetamine and synthetic cathinones), have more than doubled over the same time from fewer than 10,000 in 2013, to over 24,000 in 2017. Moreover, it is becoming increasingly clear that these two phenomena are not occurring in isolation, with ~50% of opioid-related deaths involving stimulants, and ~50% of stimulant-related deaths also involving opioids. Thus, the US is in the midst of a polysubstance abuse epidemic, the effects of which are increasing at an exponential rate. This research project aims to 1) determine the impact of self-administration of α-PVP during adolescence on the development of compulsive drug taking and vulnerability to opioid abuse later in life; 2) characterize the interactions between the abuse-related and toxic effects of stimulants and opioids; and 3) examine the degree to which opioid dependence and withdrawal impact the nature of the interactions between the abuse-related and toxic effects of mixtures of stimulants and opioids. Together, these studies will provide essential information about the complexities associated with the co-use of multiple substances from different pharmacological classes that will advance efforts to develop novel and effective treatments for abuse-related and toxic effects of polysubstance abuse.

项目概要/摘要 2009 年初，“特制药物”突然闯入美国消遣性药物市场。到 2011 年，“浴盐”、它们通常是合成卡西酮和咖啡因等其他药物的混合物，与许多媒体有关近 10 起事件中，有超过 20,000 人次到急诊室就诊。自推出以来，可供使用的合成卡西酮数量已从 3 种（MDPV、甲基酮和甲氧麻黄酮）超过 140。根据我们实验室和其他实验室的工作，我们现在知道，增强卡西酮的作用是连续的，甲基酮等药物的作用相对温和（可卡因 > 甲基酮），以及 MDPV 和 α-PVP 等药物，作为异常强大的强化剂，能够与可卡因或甲基苯丙胺相比，维持明显更高水平的反应。表明可卡因和合成卡西酮（例如 MDPV 和 α-PVP）的增强效果直接相关由于它们对 DAT 相对于 SERT 的选择性，我们的实验室还表明，这些增强（和毒性）效应可以通过当MDPV和甲基酮等药物与其他“浴液”联合使用时，可协同增强盐”成分，例如咖啡因。在过去的 5 年里，我们对合成药物的药理学和滥用相关影响有了很多了解。然而，在同一时期，合成毒品市场和消遣性毒品的使用情况更多 2013 年，海洛因开始取代处方阿片类药物，成为阿片类药物使用者的毒品。到 2014 年，合成阿片类药物（主要是芬太尼）充斥了市场，这些变化与阿片类药物数量翻倍同时发生。阿片类药物相关死亡的发生率从 2013 年的约 25,000 例增加到 2017 年的超过 47,000 例，其中一半以上（约 28,000 例）是与合成阿片类药物（例如芬太尼）有关的同时，与兴奋剂（例如可卡因，甲基苯丙胺和合成卡西酮）的数量在同一时间内从不足 10,000 增加了一倍多 2013 年，到 2017 年，这一数字已超过 24,000 人。此外，越来越明显的是，这两种现象并没有发生在隔离，约 50% 的阿片类药物相关死亡与兴奋剂相关，约 50% 的兴奋剂相关死亡还涉及兴奋剂因此，美国正处于多物质滥用流行之中，其影响正在以惊人的速度增加。该研究项目的目的是 1) 确定 α-PVP 自我给药的影响。青春期强迫性吸毒的发展和晚年阿片类药物滥用的脆弱性；2) 描述兴奋剂和阿片类药物的滥用相关作用和毒性作用之间的相互作用；3) 检查滥用的程度；阿片类药物依赖和戒断会影响滥用相关药物和有毒药物之间相互作用的性质这些研究将共同提供有关兴奋剂和阿片类药物混合物的影响的重要信息。与共同使用不同药理学类别的多种物质相关的复杂性将推进努力开发新颖有效的治疗方法来治疗与滥用有关的多物质滥用和毒性作用。