Effects of rTMS on Cannabis Use and Cognitive Outcomes in Schizophrenia

7.项目摘要： 大麻使用障碍（CUD）在患有 精神分裂症估计为25- 50%，这些患者的CUD 与较差的功能结局、早发精神病和 症状加重，精神病住院率较高。那里 在该人群中，很少有（如果有的话）经验证的CUD治疗方法。患者 精神分裂症还具有神经认知功能广泛缺陷， 可能会因使用大麻而产生负面影响。然而，大脑 例如重复经颅磁刺激的刺激技术 （rTMS）可能有望减少大麻的使用， 神经认知（例如，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的精神分裂症患者耐受rTMS程序， 不良事件最少，可在短期干预中保留 工作记忆缺陷，药物使用，戒断和渴望可能 通过高频（20 Hz）rTMS程序降低。建议的R21 研究将测试活性（n=20）与假手术（n=20）高频率的影响 rTMS（20 Hz）由标准Figure-8 TMS线圈提供，用于大麻使用， 共计N=48例精神分裂症和共病患者的认知结局 CUD，一项为期6周的双盲、随机、平行组对照试验。所有 受试者将接受应急管理和药物咨询 干预措施，以鼓励试验终点大麻戒断，我们有 在精神分裂症CUD人群中有效。主要结局 衡量标准是通过时间轴评估的试验终点自我报告的大麻使用情况 大麻尿液毒理学证实了这一点次要结局 测量包括神经认知结果（例如，语言记忆和学习， 工作记忆）、大麻渴求和戒断以及精神病症状 积极和消极症状量表，卡尔加里抑郁量表， 精神分裂症）。我们预测活性与假rTMS相比， 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，以及减少退缩和渴望， 精神分裂症的阳性和阴性症状。意义 这项研究的一个新的神经科学为基础的治疗共病CUD 和精神分裂症可能开发用于临床，并减轻负担 这种重要的并发症与严重的功能性 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.