Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania.
Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Aug;3(8):713-725. doi: 10.1016/j.bpsc.2018.05.004. Epub 2018 May 29.
Retrospective neuroimaging studies have suggested an association between early cannabis onset and later neurocognitive impairment. However, these studies have been limited in their ability to distinguish substance use risk factors from cannabis-induced effects on neurocognition. We used a prospective cohort design to test whether neurocognitive differences preceded cannabis onset (substance use risk model) and if early cannabis use was associated with poorer neurocognitive development (cannabis exposure model).
Participants (N = 85) completed a visuospatial working memory task during functional magnetic resonance imaging and multiple cognitive assessments (Wechsler Intelligence Scale for Children-IV, Cambridge Neuropsychological Test Automated Battery) at 12 years of age, before any reported cannabis use (baseline), and at 15 years of age (follow-up: N = 85 cognitive assessments, n = 67 neuroimaging). By follow-up, 22 participants reported using cannabis and/or failed a Δ-tetrahydrocannabinol urine screen (users).
At baseline, group differences supported a risk model. Those who would initiate cannabis use by 15 years of age had activation differences in frontoparietal (increased) and visual association (decreased) regions and poorer executive planning scores (Stockings of Cambridge) compared with noninitiators. Limited support was found for a cannabis exposure model. At follow-up, activation in the cuneus displayed a significant cannabis dose-response relationship, although neither cannabis dose nor cuneus activation was associated with cognitive performance.
The purported neurocognitive effects of early cannabis onset may not be due to cannabis initiation alone but also driven by limitations or late development of neurocognitive systems predictive of substance use. In addition, more prolonged cannabis exposure may be required to observe the cognitive effects of early cannabis onset.
回顾性神经影像学研究表明，早期大麻使用与后期神经认知障碍之间存在关联。然而，这些研究在区分物质使用风险因素与大麻对神经认知的影响方面存在局限性。我们采用前瞻性队列设计来检验神经认知差异是否先于大麻使用（物质使用风险模型），以及早期大麻使用是否与较差的神经认知发展相关（大麻暴露模型）。
参与者（N=85）在 12 岁时完成了一项视觉空间工作记忆任务，同时进行了功能磁共振成像和多项认知评估（韦氏儿童智力量表-IV、剑桥神经心理学测试自动化电池），在任何大麻使用报告之前（基线），并在 15 岁时（随访：N=85 项认知评估，n=67 项神经影像学）。随访时，22 名参与者报告使用了大麻和/或大麻四氢大麻酚尿液检测呈阳性（使用者）。
在基线时，组间差异支持风险模型。到 15 岁时会开始使用大麻的人，与非使用者相比，其额顶叶（增加）和视觉联想（减少）区域的激活存在差异，且执行计划分数（剑桥棒测验）较差。有限的证据支持大麻暴露模型。在随访时，楔前叶的激活与大麻剂量呈显著的剂量反应关系，尽管大麻剂量和楔前叶的激活都与认知表现无关。
早期大麻使用的所谓神经认知影响可能不仅仅是由于大麻的使用，还可能是由于预测物质使用的神经认知系统的局限性或发育迟缓所致。此外，可能需要更长时间的大麻暴露才能观察到早期大麻使用的认知影响。
