Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital, Imperial College London; Department of Psychosis Studies, Institute of Psychiatry, King's College London (King's Health Partners), London, United Kingdom.
Clinical Psychopharmacology Unit, Division of Psychology and Language Sciences, University College London.
Biol Psychiatry. 2014 Mar 15;75(6):470-8. doi: 10.1016/j.biopsych.2013.05.027. Epub 2013 Jun 29.
Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function.
We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA).
Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19).
These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.
大麻是全球使用最广泛的非法药物，使用者患精神病的风险增加，包括精神分裂症等精神病。物质依赖和精神分裂症都与多巴胺能功能障碍有关。虽然从未直接测试过，但有人提出，大麻使用与精神分裂症之间的联系是通过改变多巴胺能功能来介导的。
我们比较了 19 名经常使用大麻且在使用大麻时出现类精神病症状的大麻使用者和 19 名性别和年龄匹配的非使用者的多巴胺合成能力。多巴胺合成能力（以摄入率常数 [Formula: see text] 表示）通过正电子发射断层扫描和 3,4-二羟基-6-[(18)F]-氟-L-苯丙氨酸 ([(18)F]-DOPA) 进行测量。
与对照组相比，大麻使用者的纹状体（效应量：.85；t36 = 2.54，p =.016）及其关联（效应量：.85；t36 = 2.54，p =.015）和边缘亚区（效应量：.74；t36 = 2.23，p =.032）的多巴胺合成能力降低。大麻使用者与对照组相比，多巴胺合成能力的组间差异是由那些符合大麻滥用或依赖标准的使用者驱动的。多巴胺合成能力与较高的大麻使用水平呈负相关（r = -.77，p <.001），与大麻使用起始年龄呈正相关（r =.51，p =.027），但与大麻引起的类精神病症状无关（r =.32，p =.19）。
这些发现表明，慢性大麻使用与多巴胺合成能力降低有关，并对大麻通过诱导与精神分裂症相同的多巴胺改变来增加精神病风险的假设提出质疑。
