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

• 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
• 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

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.

摘要 目前迫切需要开发新的药物治疗酒精使用障碍（AUD）。最近， 迷幻化合物在治疗不同的精神疾病中引起了极大的关注， 他们报告的快速和持久的影响。来自观察性研究的初步证据，支持 通过动物研究，有希望用于迷幻剂N，N-二甲基色胺的潜在治疗效果 (DMT)为AUD。在这里，我们建议调查的治疗潜力，单剂量的静脉注射DMT 加上一个简短的心理治疗课程（包括动机增强疗法（MET））对酒精 在一项概念验证、随机化（1：1）、安慰剂- 对照、双盲、平行组、实验室研究和临床试验。 方法：诊断为中度至重度AUD（基于DSM 5）的健康个体将被 随机接受单剂量静脉内DMT或活性安慰剂（苯海拉明）。生命体征 密切监测，将使用视觉疼痛量表（VAS）和DMT急性 迷幻效果将使用神秘体验问卷（MEQ）进行评估，在结束时， 给药日。将使用治疗后出现的不良事件的系统性评估来评估不良事件 在给药日和每周随访期（4周）进行效果（SAFTEE）访谈。后一天 药物管理，参与者将参加一个实验会议，使用酒精饮用模式（ADP）。 所有参与者将在实验开始时消耗启动剂量的酒精， 随后是两个1小时的自我管理饮酒会议，参与者将有一个选择， 总共喝了8杯饮料，或者每喝一杯没有喝的饮料就得到5美元。的总数 消费饮料是主要的主要结果。所有参与者将接受一个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）对参与者的自然酒精的影响 使用时间轴追踪（TLFB），每周消耗一次，持续4周，以测量重蛋白质的百分比。 饮酒天数、戒酒天数、饮酒总量和 将比较戒酒、不大量饮酒和世卫组织饮酒风险降低2级。 假设：相对于对照组（苯海拉明，IV，25 mg + MET）， 在患有AUD的个体中，静脉内（IV）DMT（0.3 mg/kg）加简短的心理治疗（包括MET）将1） 安全且耐受性良好，2）减少在实验室中使用酒精饮料测量的酒精消耗量 范例，第二天，和3）在接下来的4周内减少饮酒。