MDMA as a Treatment for Social Deficits in Schizophrenia

MDMA 作为精神分裂症社交缺陷的治疗方法

• 批准号: 10696852
• 负责人: Anya K Bershad
• 金额: $ 39.26万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696852
• 关键词: Acute; Address; Amphetamines; Antipsychotic Agents; Attention; Behavioral; Biological Psychiatry; Biostatistics Core; California; Center for Translational Science Activities; Clinical; Clinical Trials; Crossover Design; Cues; Delusions; Department chair; Dose; Empathy; Faculty; Feeling; Foundations; Funding; Future; Goals; Grant; Hallucinations; Hormones; Hour; Human; Impairment; Individual; Institution; Intervention; Investigation; Journals; Laboratories; Lead; Los Angeles; Measures; Mental disorders; Mentorship; Methodology; Motivation; Oxytocin; Paper; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Phase; Placebos; Plasma; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Property; Psychiatry; Psychopharmacology; Psychotropic Drugs; Publications; Publishing; Research; Research Design; Research Personnel; Schedule; Schizophrenia; Science; Secondary to; Secure; Social Functioning; Speech; Symptoms; Testing; Therapeutic; Time; Universities; Work; attentional bias; behavioral pharmacology; biobehavior; data management; disability; disabling symptom; ecstasy; effective therapy; experience; faculty mentor; follow-up; functional disability; healthy volunteer; indexing; innovation; meetings; neuropsychiatry; neuropsychopharmacology; novel; open label; patient population; pharmacologic; professor; programs; psychopharmacologic; psychosocial; psychostimulant; psychotic symptoms; randomized placebo controlled trial; senior faculty; social; social attachment; social attention; social deficits; social engagement; symptom treatment

Project Summary/Abstract Impaired social motivation, or “asociality,” is a negative symptom of schizophrenia and a cause of significant functional impairment in the illness. Whereas many symptoms of schizophrenia can be treated with antipsychotic medications, deficits in social motivation persist, leading to significant social disability in patients. There is currently no effective treatment for this symptom of the illness. One promising and unexplored avenue to enhance social motivation in schizophrenia is ± 3,4-methylenedioxymethamphetamine (MDMA). MDMA is a psychostimulant that shares some pharmacological properties with amphetamines, but in addition, has pronounced pro-social effects, increasing the motivation to engage socially. In healthy volunteers, it produces feelings of empathy and closeness with others and increases attention to positive social cues, perhaps partly through its effects on the social bonding hormone, oxytocin. MDMA has shown promise in other psychiatric conditions such as PTSD. Thus, MDMA could offer a unique therapeutic benefit in patients with schizophrenia who suffer from impaired social motivation. We plan to test the hypothesis that MDMA enhances social motivation in patients with schizophrenia by conducting a two-phase study. The first phase (Aim 1) will be an open-label, ascending-dose, within-subject trial in which participants will receive 40mg, 80mg, or 120mg of MDMA. The doses will be administered in ascending order, but doses will be stopped if subjects experience moderate or greater psychotic symptoms at 24 hours. This trial will assess the tolerability of the drug in this population and guide in the selection of a maximum well-tolerated dose for the second phase. The primary tolerability measure will be clinician-rated psychotic symptoms (disorganized speech, delusions, hallucinations) collected at 24 hours after MDMA administration. Phase 2 (Aim 2) will be a randomized, placebo-controlled trial using a crossover design to test the acute effects of MDMA on social motivation and plasma oxytocin in patients with schizophrenia. Social motivation will be assessed using a social attention bias task (ABT), which has been validated in MDMA trials with healthy volunteers, in addition to secondary behavioral and self-report measures of social motivation. The results of this project will lay the foundation for further investigations of MDMA and other psychoactive compounds as a treatment for debilitating and difficult-to-treat social deficits in schizophrenia. Future studies will examine interactions between the effects of psychoactive compounds and nonpharmacologic psychosocial interventions targeting social symptoms.

项目总结/摘要 受损的社会动机，或“社会性”，是精神分裂症的一种阴性症状，也是精神分裂症的一个重要原因。 疾病中的功能障碍。然而精神分裂症的许多症状可以用 抗精神病药物治疗后，社会动机的缺陷持续存在，导致患者严重的社会残疾。 目前还没有有效的治疗这种疾病的症状。一个有前途的未开发的途径 提高精神分裂症患者社会动机的药物是± 3，4-亚甲二氧基甲基苯丙胺（MDMA）。MDMA是一种 精神兴奋剂与安非他明有一些药理学特性，但除此之外， 显著的亲社会效应，增加了参与社会的动机。在健康的志愿者中， 同情心和与他人的亲密感，并增加对积极的社会线索的关注，也许部分 通过它对社会联系荷尔蒙催产素的影响。MDMA在其他精神病治疗中显示出希望 如PTSD。因此，MDMA可以为精神分裂症患者提供独特的治疗益处 他们的社会动机受损我们计划测试MDMA增强社交能力的假设 精神分裂症患者的动机进行了两阶段的研究。第一阶段（目标1）将是 开放标签、递增剂量、受试者内试验，受试者将接受40 mg、80 mg或120 mg的 摇头丸剂量将按升序给药，但如果受试者出现以下情况，则将停止给药 24小时内出现中度或重度精神病症状。这项试验将评估药物的耐受性， 在选择第二阶段的最大耐受剂量时，人群和指导。主 耐受性指标将是临床医生评定的精神病症状（言语紊乱、妄想、幻觉） 在MDMA给药后24小时收集。II期（目标2）将是一项随机化、安慰剂对照 使用交叉设计试验，以测试MDMA对社会动机和血浆催产素的急性影响， 精神分裂症患者社会动机将使用社会注意力偏见任务（ABT）进行评估， 已在健康志愿者的MDMA试验中得到验证，除了次要行为和自我报告外， 社会动机的衡量标准。本项目的研究结果将为进一步研究 MDMA和其他精神活性化合物用于治疗老年人衰弱和难以治疗的社交缺陷 精神分裂症未来的研究将检查精神活性化合物的作用之间的相互作用， 针对社会症状的非药物心理社会干预。