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 迫切需要开发新的药物治疗酒精使用障碍(AUD)。最近， 迷幻化合物在治疗以下不同精神障碍方面引起了极大的关注 据报道，它们的作用迅速且持久。来自观察性研究的初步证据，支持 动物实验表明，迷幻剂N，N-二甲基色胺具有潜在的治疗作用 (DMT)表示澳元。在这里，我们建议研究单剂静脉注射DMT的治疗潜力。 外加一次简短的酒精心理疗法(包括动机强化疗法) 未寻求治疗的AUD患者的摄入量，概念验证，随机(1：1)，安慰剂- 对照、双盲、平行组、实验室研究和临床试验。 方法：否则，被诊断为中到重度AUD(基于DSM5)的健康个人将被 随机接受单剂量静脉注射DMT或活性安慰剂(苯海拉明)。生命体征将会 严密监控的耐受性将使用视觉模拟标尺(VAS)和DMT急性 迷幻效果将使用神秘体验问卷(MEQ)在结束时进行评估 服药日。将使用治疗紧急事件系统评估来评估不良事件 在给药日和每周随访(4周)时进行效果(SAFTEE)访谈。接下来的一天 在药物管理方面，参与者将参加一个使用酒精饮酒范式(ADP)的实验会议。 所有参与者都将在实验开始时饮用预备量的酒精，这将 之后是两个1小时的自我给药饮酒会议，参与者将在其中选择 总共消费8杯饮料或每杯未消费的饮料获得5美元。总人数 饮品消费是主要的主要结果。所有参与者都将接受简短的心理治疗。 (包括MET)。我们将探索DMT(加上短暂的心理治疗)对参与者天然酒精的影响 每周消费4周，使用时间线回访(TLFB)来测量体重百分比 饮酒天数、禁酒天数和饮酒总量以及 禁酒、不大量饮酒和世卫组织饮酒风险降低2级将进行比较。 假设：相对于对照组(苯海拉明，静脉注射，25毫克加MET)，单次迷幻剂量的 静脉注射DMT(0.3 mg/kg)加简单心理治疗(包括MET)治疗AUD患者将1) 安全和耐受性良好，2)减少在实验室通过饮酒测量的酒精消耗量 范例，第二天，以及3)在接下来的4周内减少饮酒。