Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users
Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users
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DOI：
10.1089/can.2017.0047
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发表时间：
2018-01-01
影响因子：
3.8
通讯作者：
Solowij, Nadia
中科院分区：
文献类型：
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作者：
Beale, Camilla;Broyd, Samantha J.;Solowij, Nadia
简介：慢性大麻使用与海马体的神经解剖学改变有关。虽然大麻使用的不利影响通常归因于Delta（9）-四氢大麻酚，但新出现的自然证据表明大麻二酚（CBD）具有神经保护作用，可能会改善与大麻使用相关的脑损伤，包括保护海马体积损失。这项研究探讨了在社区内对常规大麻使用者长期给予CBD是否可以逆转或减少与慢性大麻使用相关的特征性海马损害。材料与方法：18名经常使用大麻的人参加了一项类似于10周的开放标签实用性试验，该试验涉及每日口服200 mg CBD，没有要求改变他们正在使用的大麻。参与者在基线和CBD治疗后使用结构磁共振成像进行评估。进行自动纵向海马分割以评估整个海马和12个子域内的体积变化。结果：左、右侧海马整体无明显变化。然而，左下托复合体（下托旁、下托前和下托）体积从基线至治疗后显著增加（p=0.017，未校正）1.58%（Cohen d=0.63;下托旁2.83%）。重大麻用户表现出显着的增长，在左下托复合体，主要是在前下托，和右角ammonis（CA）1相比，较轻的用户。更大的右下托复合体和总海马体积和更高的血浆CBD浓度之间的关联是明显的，特别是在重度使用者中。结论：我们的研究结果表明，CBD对当前大麻使用者的下托和CA 1子领域具有恢复作用，特别是那些终生接触大麻的人。虽然在一项更大的安慰剂对照试验中需要复制，但这些发现支持CBD对慢性大麻使用所带来的大脑结构损害的保护作用。此外，这些结果表明，CBD可能是治疗大麻依赖的有用辅助剂，并且可能治疗以海马病理学为特征的一系列临床疾病（例如，精神分裂症、阿尔茨海默病和重度抑郁症）。
Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Delta (9)-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use. Materials and Methods: Eighteen regular cannabis users participated in an similar to 10-week open-label pragmatic trial involving daily oral administration of 200mg CBD, with no change to their ongoing cannabis use requested. Participants were assessed at baseline and post-CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields. Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen's d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users. Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer's disease, and major depressive disorder).