Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis
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DOI：
10.1001/archgenpsychiatry.2009.17
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发表时间：
2009-04-01
影响因子：
--
通讯作者：
McGuire, Philip
中科院分区：
文献类型：
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作者：
Bhattacharyya, Sagnik;Fusar-Poli, Paolo;McGuire, Philip
背景：大麻的使用会损害语言学习，引发急性精神病，并增加精神分裂症的风险。目前还不清楚大麻在人脑中调节语言学习和诱发精神病症状的作用机制。目的：研究大麻的两种主要精神活性成分Δ 9-四氢大麻酚（Delta 9-tetrahydrocannabinol）对语言学习和诱发精神病症状的作用（Delta 9-THC）和大麻二酚对言语配对联想学习过程中局部脑功能的影响。设计：受试者在3个不同的场合进行了研究，使用块设计功能磁共振成像范式，同时执行口头配对联想学习任务。每次成像之前，在双盲、随机、安慰剂对照、重复测量、受试者内设计中，摄入Delta 9-THC（10 mg）、大麻二酚（600 mg）或安慰剂。十五个健康的，母语是英语的，右利手的白色人种/种族的男性，使用大麻15次或更少，并且一生中接触其他非法药物的次数最少。局部大脑激活（血氧水平依赖性反应）、言语学习任务中的表现以及精神病症状、焦虑、中毒和镇静的客观和主观评级。δ 9-四氢大麻酚增加了精神病症状和焦虑、中毒和镇静的水平，而给予大麻二酚后对这些参数没有显着影响。在口头学习任务的性能没有显着调制的药物。在第2和第3块期间，Delta 9-THC的给药增强了海马旁回的激活，使得在重复编码块中激活的正常线性递减不再明显。Delta 9-Tetrahydrocannabinol也减弱了正常的腹侧纹状体激活的时间依赖性变化，在检索的单词对，这是直接相关的并发诱导的精神病症状。相反，大麻二酚的管理没有这样的effect.Conclusion：调制的中颞叶和腹侧纹状体功能的Delta 9-THC可能是C sativa的影响，分别对语言学习和精神病症状。
Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms.Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning.Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design.Setting: University research center.Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime.Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation.Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect.Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.