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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要社交动机受损，或“不合群”，是精神分裂症的一种负面症状，也是严重影响精神分裂症的一个原因。然而，精神分裂症的许多症状都可以治疗。抗精神病药物治疗后，社交动机持续存在缺陷，导致患者出现严重的社交障碍。目前还没有一种有效的方法来治疗这种疾病的症状。增强精神分裂症的社会动机是±3,4-亚甲二氧基甲基苯丙胺（MDMA）。精神兴奋剂，与安非他明具有某些相同的药理特性，但除此之外，它产生显着的亲社会效应，增加健康志愿者参与社会的动力。与他人产生同理心和亲密感，并增加对积极社交暗示的关注，这可能在一定程度上通过其对社会联系激素的影响，催产素在其他精神科疾病中显示出良好的前景。因此，MDMA 可以为精神分裂症患者提供独特的治疗益处。我们计划检验 MDMA 增强社交能力的假设。通过进行两阶段研究来提高精神分裂症患者的动机第一阶段（目标 1）将是一项开放标签、剂量递增、受试者内试验，参与者将接受 40 毫克、80 毫克或 120 毫克 MDMA 剂量将按升序给药，但如果受试者出现这种情况，剂量将停止。 24小时内出现中度或以上精神病症状该试验将评估该药物在此情况下的耐受性。人群并指导选择第二阶段的最大耐受剂量。耐受性测量将是临床医生评定的精神病症状（言语混乱、妄想、幻觉）第 2 阶段（目标 2）在 MDMA 给药后 24 小时收集的数据将是随机、安慰剂对照的。使用交叉设计来测试 MDMA 对社交动机和血浆催产素的急性影响的试验精神分裂症患者的社会动机将使用社会注意力偏差任务（ABT）进行评估。除了次要行为和自我报告之外，已在健康志愿者的 MDMA 试验中得到验证该项目的结果将为进一步研究奠定基础。 MDMA 和其他精神活性化合物可用于治疗衰弱和难以治疗的社交缺陷未来的研究将探讨精神活性化合物与精神分裂症之间的相互作用。针对社会症状的非药物心理社会干预措施。