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）的新型药理学治疗。最近，迷幻化合物在治疗不同的精神疾病时引起了极大的关注他们报告的快速作用和持久效应。观察性研究的初步证据，支持通过动物研究，有望可以对迷幻N，N-二甲基丁胺的潜在治疗作用（DMT）aud。在这里，我们建议研究单剂量静脉DMT的治疗潜力加上短暂的心理治疗过程（包括酒精的动机增强疗法（MET））在概念验证，随机分析（1：1）中，寻求AUD的人的非治疗中的消费量，安慰剂 - 受控，双盲，并行组，实验室研究和临床试验。方法：否则健康的个体患有中度至重度AUD（基于DSM5）的健康个体将是随机分配单剂量的静脉内DMT或活性安慰剂（二苯胺）。生命将是密切监测，将使用视觉模拟量表（VAS）和DMT急性测量耐受性迷幻效果将在结束时使用神秘经验问卷（MEQ）评估给药日。不良事件将使用系统评估进行评估以进行治疗效果（SAFTEE）在剂量日和每周的随访（4周）中访谈。随后的一天药物管理局，参与者将使用酒精饮酒范式（ADP）参加实验会议。所有参与者将在实验会议开始时食用一定剂量的酒精，这将其次是两个1小时的自我管理饮酒课程，参与者可以选择每种未消费的饮料总共喝了8杯或获得5美元。总数消费饮料是主要的主要结果。所有参与者将获得简短的心理治疗课程（包括Met）。我们将探讨DMT（加简短的心理治疗）对参与者天然酒精的影响每周消费4周，使用时间轴跟随后卫（TLFB）来测量重量的百分比饮酒日，戒酒日，饮酒总量和分类结果将比较禁欲，没有大量饮酒和2级降低饮酒风险。假设：相对于对照（Diphenhydramine，IV，25 mg Plus Met），单个迷幻剂量静脉注射（IV）DMT（0.3 mg/kg）加上AUD个人的简短心理疗法（包括MET）将为1）安全且耐受性良好，2）减少使用酒精饮酒在实验室中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。