Effects of rTMS on Cannabis Use and Cognitive Outcomes in Schizophrenia

7.项目总结： 大麻使用障碍(CUD)在吸毒者中的患病率 据估计，精神分裂症的发病率为25%-50%，而这些患者的CUD 与较差的功能结局、较早的精神病发作和 症状加重，精神病院住院率较高。那里 在这一人群中，几乎没有有效的治疗CUD的方法。患有疾病的患者 精神分裂症也有广泛的神经认知功能缺陷， 可能会被大麻的使用以消极的方式改变。然而，大脑 重复经颅磁刺激等刺激技术 (RTMS)可能对减少大麻使用和改善大麻状况抱有希望 精神分裂症患者的神经认知(如工作记忆、注意力) 我们实验室和其他地方的初步经验表明， 合并CUD的精神分裂症患者可以耐受rTMS手术 最小的不良事件，可以在短期干预中保留 试验，以及工作记忆缺陷、药物使用、戒断和渴求可能 通过高频(20赫兹)rTMS程序减少。建议的R21 研究将测试活动(n=20)和假(n=20)高频的影响 RTMS(20赫兹)，由标准的8字形TMS线圈提供，关于大麻的使用和 N=48例精神分裂症及其合并症患者的认知结果 CUD，进行为期6周的双盲、随机、平行分组对照试验。全 受试者将接受应急管理和药物咨询 鼓励试验终点大麻戒除的干预措施，我们有 在精神分裂症患者中被证明是有效的。主要结果是 措施将是由时间表评估的试验终点自我报告的大麻使用情况 经大麻尿毒学证实的随访结果。次要结果 衡量标准包括神经认知结果(例如，言语记忆和学习， 工作记忆)、对大麻的渴望、戒断和精神病症状 评分(阳性和阴性症状量表，卡尔加里抑郁量表 精神分裂症)。我们预测，与假rtms相比，活动rtms将显著 减少大麻使用，增加试验终点阴性大麻尿 频率，并改善神经认知结果，如语言学习和 记忆和工作记忆，以及退缩和渴望的减少， 精神分裂症的阳性和阴性精神病症状。它的意义 这项研究的意义在于，一种基于神经科学的治疗共病线索的新方法 而精神分裂症可以开发用于临床，减轻负担 与严重的功能性疾病相关的这种重要的共病 精神分裂症的损害。

7. Project Summary: The prevalence of cannabis use disorder (CUD) in people with schizophrenia is estimated to be 25-50%, and CUD in these patients is associated with poorer functional outcomes, early onset of psychosis and symptoms exacerbation, and higher rates of psychiatric hospitalization. There are few, if any, validated treatments for CUD in this population. Patients with schizophrenia also have wide-ranging deficits in neurocognitive function, which may be altered by cannabis use in a negative manner. However, brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) may hold promise for reducing cannabis use and improving neurocognition (e.g., working memory, attention) in patients with schizophrenia. Preliminary experience from our laboratory and elsewhere have shown that schizophrenia patients with co-morbid CUD tolerate rTMS procedures with minimal adverse events, that they can be retained in short-term intervention trials, and that working memory deficits, drug use, withdrawal and craving may be reduced by high-frequency (20 Hz) rTMS procedures. The proposed R21 study would test the effects of active (n=20) versus sham (n=20) high frequency rTMS (20 Hz) delivered by a standard Figure-8 TMS coil on cannabis use and cognitive outcomes in a total of N=48 patients with schizophrenia and co-morbid CUD, in a 6-week, double-blind, randomized, parallel groups controlled trial. All subjects would receive contingency management and drug counseling interventions to encourage trial endpoint cannabis abstinence, which we have shown to be effective in the schizophrenia CUD population. The primary outcome measure would be trial endpoint self-reported cannabis use assessed by timeline follow-back confirmed by cannabis urine toxicology. Secondary outcome measures include neurocognitive outcomes (e.g., verbal memory and learning, working memory), cannabis craving and withdrawal and psychosis symptom ratings (Positive and Negative Symptoms Scale, Calgary Depression Scale for Schizophrenia). We predict that active versus sham rTMS would significantly reduce cannabis use and increase trial endpoint negative cannabis urine frequency, and improve neurocognitive outcomes such as verbal learning and memory and working memory, as well as reductions in withdrawal and craving, positive and negative symptoms of psychosis in schizophrenia. The significance of this study is that a novel neuroscience-based treatment for co-morbid CUD and schizophrenia may be developed for use in the clinic, and reduce the burden of this important co-morbidity which is associated with serious functional impairment in schizophrenia.