PDF(Pubmed)
Abstract：
Adolescent individuals often present with subtle, sub-threshold psychiatric syndromes that fluctuate or persist for years. These symptoms have been classified as Clinically High-Risk mental states (CHR), negatively affecting these individuals\' psychosocial development and integration by reducing performance and affecting interpersonal relations. The pathophysiological underpinnings have not been studied in detail, contributing to the current lack of appropriate intervention strategies. This case report sheds new light on potential pathophysiological mechanisms of this condition, which may be addressed by novel treatment approaches such as cannabidiol. A 19-year-old student presented to our early intervention center with a marked cognitive decline within 6 months, anhedonia, ambivalence, social withdrawal, poverty of speech, and brief intermittent psychotic symptoms (delusions and hallucinations). He was diagnosed with CHR state, and we decided to treat him with the non-psychotomimetic phytocannabinoid cannabidiol. Cannabidiol is a promising compound carrying an orphan drug approval for rare certain childhood epilepsy types and is under investigation as an antipsychotic compound with a new mechanism of action compared to existing antipsychotics. We investigated the effect of oral cannabidiol (600 mg per day) over 4 weeks on psychopathology and cerebral glucose utilization. We observed no relevant side effects but a significant clinical improvement. In addition, positron emission tomography (PET) showed a considerable increase in cerebral [18F]fluoro-2-deoxyglucose (FDG) uptake in various brain regions. This finding suggests that cannabidiol may enhance cerebral glucose utilization, possibly via activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) by its endogenous ligand anandamide or related N-acylethanolamines. This mechanism may represent a new innovative treatment approach for CHR, especially given that many individuals with CHR and early psychosis do not substantially benefit from current psychopharmacological interventions.
摘要：
青少年个体经常出现微妙的，波动或持续多年的亚阈值精神病综合征。这些症状被归类为临床高危精神状态（CHR）。通过降低绩效和影响人际关系，对这些个体的心理社会发展和融合产生负面影响。病理生理基础尚未详细研究，导致目前缺乏适当的干预策略。该病例报告揭示了这种情况的潜在病理生理机制，这可以通过新的治疗方法如大麻二酚来解决。一名19岁的学生出现在我们的早期干预中心，在6个月内出现了明显的认知能力下降，快感缺失,矛盾心理,社会退出,言语贫困，和短暂的间歇性精神病症状（妄想和幻觉）。他被诊断出患有CHR状态，我们决定用非精神分裂植物大麻素大麻二酚治疗他。大麻二酚是一种有前途的化合物，具有某些罕见的儿童癫痫类型的孤儿药批准，并且正在研究作为抗精神病化合物，与现有的抗精神病药相比具有新的作用机制。我们调查了4周内口服大麻二酚（每天600mg）对精神病理学和脑葡萄糖利用的影响。我们没有观察到相关的副作用，但有显著的临床改善。此外,正电子发射断层扫描（PET）显示各个大脑区域的大脑[18F]氟-2-脱氧葡萄糖（FDG）摄取显着增加。这一发现表明，大麻二酚可以提高脑葡萄糖的利用率，可能通过内源性配体anandamide或相关的N-酰基乙醇胺激活过氧化物酶体增殖物激活受体γ（PPAR-γ）。这种机制可能代表了CHR的一种新的创新治疗方法，特别是考虑到许多CHR和早期精神病患者并没有从当前的精神药理学干预中获得实质性益处。
