PILOT STUDY OF MARIJUANA INDUCED DEPERSONALIZATION DISORDER

大麻引起的人格解体的试点研究

• 批准号: 7380577
• 负责人: DAPHNE SIMEON
• 金额: $ 0.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380577
• 关键词: Cannabis; aging; anxiety; association cortex; brain imaging /visualization /scanning; cannabinoid receptor; cannabinoids; depression; dexamethasone; endogenous opioid; gene mutation; genes; genetics; identity; memory; perception; personality disorders; robotics; sex; stress; suppression; trauma

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aim: To identify mutations of the cannabinoid receptor gene CB1/Cnr1 that may be associated with the vulnerability towards developing chronic depersonalization after the isolated ingestion of marijuana. Depersonalization disorder (DPD) is a dissociative disorder characterized by prominent depersonalization and often derealization, without clinical memory or identity alterations. Depersonalization is a particular type of dissociation that involves a disruption of subjective self-perceptions, manifested in symptoms such as feeling detached, robotic, out-of-body, or otherwise disconnected from one's self. The disorder has an approximately 1:1 gender ratio with mean onset around 16 years of age. The course is typically chronic and often continuous. Mood, anxiety and personality disorders are often comorbid with DPD but none predict symptom severity. The most common proximal precipitants of the disorder are severe stress, depression, panic, marijuana and hallucinogen ingestion. DPD has also been associated with more distal childhood interpersonal trauma, in particular emotional abuse and neglect. Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid, NMDA and cannabinoid pathways. Depersonalization has also been associated with autonomic blunting and resistance to dexamethasone suppression. Brain imaging studies in DPD have revealed widespread alterations in metabolic activity in the sensory association cortex, as well as prefrontal hyperactivation and limbic inhibition in response to emotional stimuli. To date there are no established pharmacological or psychotherapeutic treatments for the disorder. In a notable minority of 10-20 % of individuals with DPD, chronic depersonalization lasting for months, years or decades is initially triggered by the sporadic, sometimes even one-time use, of marijuana. This well-described and documented phenomenon is highly suggestive of a genetic vulnerability in cannabinoid-related neurochemical pathways in such individuals. The goal, therefore, of this pilot study is to explore this hypothesis, by demonstrating feasibility to conduct the study and generating preliminary genetics findings for future grant submission.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。具体目标：确定大麻素受体基因 CB1/Cnr1 的突变，该突变可能与单独摄入大麻后发生慢性人格解体的脆弱性有关。人格解体障碍（DPD）是一种解离性障碍，其特征是显着的人格解体和现实解体，没有临床记忆或身份改变。人格解体是一种特殊类型的解离，涉及主观自我认知的破坏，表现为感觉分离、机器人、灵魂出窍或以其他方式与自我脱节等症状。该疾病的性别比例约为 1:1，平均发病年龄约为 16 岁。该病程通常是慢性的并且通常是连续的。情绪、焦虑和人格障碍通常与 DPD 共存，但都不能预测症状的严重程度。该疾病最常见的近端诱因是严重的压力、抑郁、恐慌、吸食大麻和致幻剂。 DPD 还与更远期的童年人际创伤有关，特别是情感虐待和忽视。神经化学结果表明可能涉及血清素能、内源性阿片类药物、NMDA 和大麻素途径。人格解体也与自主神经迟钝和对地塞米松抑制的抵抗有关。 DPD 的脑成像研究揭示了感觉关联皮层代谢活动的广泛改变，以及对情绪刺激的反应的前额叶过度激活和边缘抑制。迄今为止，还没有针对该疾病的既定药物或心理治疗方法。 在 10-20% 的 DPD 患者中，有一小部分人的慢性人格解体持续数月、数年或数十年，最初是由偶尔、有时甚至是一次性吸食大麻引发的。这种被充分描述和记录的现象高度表明这些个体中大麻素相关的神经化学途径存在遗传脆弱性。因此，这项试点研究的目标是通过证明进行研究的可行性并为未来提交资助提供初步的遗传学研究结果来探索这一假设。