The potential therapeutic effects of N, N-dimethyltryptamine (DMT) on alcohol use disorder (AUD)

N,N-二甲基色胺（DMT）对酒精使用障碍（AUD）的潜在治疗作用

基本信息

批准号：
10668109
负责人：
Anahita Bassir Nia
金额：
$ 18.82万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10668109
关键词：
Abstinence Acute Adverse event Alcohol consumption Alcohols Animals Anxiety Attention Back Banisteriopsis Binding Brief Psychotherapy Cause of Death Clinical Clinical Trials Consumption DSM-V Development Diagnosis Diphenhydramine Dose Double-Blind Method Ethanol FDA approved HTR2A gene Hallucinogens Heavy Drinking Hospitals Hour Human Indigenous Individual Interview Intravenous Laboratories Laboratory Study Literature Long-Term Effects Lysergic Acid Diethylamide Measures Medical Medicine Mental Depression Mental disorders Meta-Analysis Methodology Methods Monitor Mus N,N-Dimethyltryptamine Observational Study Odds Ratio Oral Administration Outcome Outpatients Participant Patient Self-Report Pharmaceutical Preparations Pharmacological Treatment Phase Placebo Control Placebos Psilocybin Psychotherapy Questionnaires Randomized Randomized Controlled Clinical Trials Reporting Risk Safety Sample Size Self Administration South American Substance Use Disorder Tea Therapeutic Therapeutic Effect Tribes United States Visual Woman alcohol abuse therapy alcohol measurement alcohol use disorder analog anxiety reduction anxiety symptoms behavioral sensitization comparison control conditioned place preference consumption measures depressive symptoms drinking efficacy evaluation experience follow-up improved interest intravenous administration men motivational enhancement therapy novel preclinical study primary outcome psychoeducation psychoeducational timeline

项目摘要

ABSTRACT There is an urgent need to develop novel pharmacological treatment for alcohol use disorder (AUD). Recently, psychedelic compounds have attracted great attention in treatment of different psychiatric disorders following their reported fast-acting and long-lasting effects. Preliminary evidence from observational studies, supported by animal studies, is promising for the potential therapeutic effects of psychedelic N,N-dimethyltryptamine (DMT) for AUD. Here, we propose to investigate the therapeutic potential of a single dose of intravenous DMT plus a brief course of psychotherapy (including Motivational Enhancement Therapy (MET)) on alcohol consumption in non-treatment seeking individuals with AUD, in a proof-of-concept, randomized (1:1), placebo- controlled, double-blind, parallel group, laboratory study and clinical trial. Methods: Otherwise healthy individuals with diagnosis of moderate to severe AUD (based on DSM5) will be randomized to receive a single dose of intravenous DMT or active placebo (diphenhydramine). Vitals will be closely monitored, tolerability will be measured using a Visual Analogue Scale (VAS), and DMT acute psychedelic effects will be assessed using the Mystical Experience Questionnaire (MEQ), at the end of the dosing day. Adverse events will be assessed using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview on the dosing day and weekly follow up sessions (4 weeks). One day following drug administration, participants will attend an experimental session using Alcohol Drinking Paradigm (ADP). All participants will consume a priming dose of alcohol at the beginning of the experimental session, which will be followed by two 1-hour self-administration drinking sessions, over which participants will have a choice of consuming a total of 8 drinks or receiving $5 for each drink that is not consumed. The total number of consumed drinks is the main primary outcome. All participants will receive a brief course of psychotherapy (including MET). We will explore the effects of DMT (plus brief psychotherapy) on participants' natural alcohol consumption weekly for 4 weeks, using Timeline follow-back (TLFB), to measure the percentage of heavy drinking days, abstinent days, and total amount of alcohol consumption and categorical outcomes of abstinence, no heavy drinking and a 2-level reduction in WHO drinking risk will be compared. Hypotheses: Relative to control (diphenhydramine, IV, 25 mg plus MET), a single psychedelic dose of intravenous (IV) DMT (0.3 mg/kg) plus brief psychotherapy (including MET) in individuals with AUD will 1) be safe and well-tolerated, 2) reduce alcohol consumption measured in the laboratory using Alcohol Drinking Paradigm, the day after, and 3) reduce alcohol drinking over the following 4 weeks.

抽象的迫切需要开发针对酒精使用障碍（AUD）的新型药物治疗方法。最近，迷幻化合物在治疗不同精神疾病方面引起了广泛关注据报道，它们具有快速起效和持久的效果。观察性研究的初步证据支持通过动物研究，迷幻剂 N,N-二甲基色胺的潜在治疗效果有望实现（DMT）为澳元。在这里，我们建议研究单剂量静脉注射 DMT 的治疗潜力加上针对酒精的简短心理治疗（包括动机增强疗法（MET））在概念验证、随机（1:1）、安慰剂中，非治疗寻求 AUD 个体的消费对照、双盲、平行组、实验室研究和临床试验。方法：否则，诊断为中度至重度 AUD（基于 DSM5）的健康个体将被随机接受单剂量静脉注射 DMT 或活性安慰剂（苯海拉明）。生命体征将是密切监测，耐受性将使用视觉模拟量表（VAS）和DMT急性测量迷幻效果将在实验结束时使用神秘体验问卷（MEQ）进行评估给药日。将使用紧急治疗系统评估来评估不良事件给药日和每周随访（4 周）的效果 (SAFTEE) 访谈。一天后药物管理期间，参与者将参加使用酒精饮酒范式（ADP）的实验课程。所有参与者将在实验开始时饮用启动剂量的酒精，这将接下来是两次 1 小时的自我管理饮酒课程，参与者可以选择总共喝了 8 杯饮料，或者每未喝完饮料就收到 5 美元。总数消耗的饮料是主要的主要结果。所有参与者都将接受简短的心理治疗课程（包括 MET）。我们将探讨 DMT（加上简短的心理治疗）对参与者自然酒精的影响每周消耗量，持续 4 周，使用时间线追踪 (TLFB) 来衡量重度摄入量的百分比饮酒天数、戒酒天数、饮酒总量以及分类结果将比较戒酒、不酗酒和世界卫生组织饮酒风险降低 2 级的情况。假设：相对于对照（苯海拉明，静脉注射，25 毫克加 MET），单次迷幻剂量的对于 AUD 患者，静脉注射 (IV) DMT（0.3 mg/kg）加短暂心理治疗（包括 MET）将 1) 安全且耐受性良好，2) 通过饮酒减少实验室测量的酒精消耗量范式、第二天和 3) 在接下来的 4 周内减少饮酒。