Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.
Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.
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DOI：
10.1111/adb.13085
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Tolliver, Bryan K.
中科院分区：
文献类型：
--
作者：
Prisciandaro, James J.;Mellick, William;Squeglia, Lindsay M.;Hix, Sara;Arnold, Lauren;Tolliver, Bryan K.
脑γ-氨基丁酸（GABA）/谷氨酸稳态的破坏是双相情感障碍（BD）和大麻使用障碍（CUD）并存的药物干预的一个有前途的目标。加巴喷丁是一种安全且耐受性良好的药物，FDA批准用于治疗其他神经系统疾病，恢复GABA/谷氨酸稳态，治疗研究支持治疗CUD以及BD和CUD常见的焦虑和睡眠障碍的疗效。本手稿代表了一项加巴喷丁（1200 mg/天）治疗BD+CUD（n=22）的随机、双盲、安慰剂对照、交叉（1周/条件）、多模态MRI（质子-MR波谱，功能性MRI）初步研究的主要报告。初步分析显示，A）加巴喷丁耐受性良好，粘附性和保留性高，B）加巴喷丁增加背侧前扣带皮层（dACC）和右侧基底神经节（rBG）谷氨酸水平，C）加巴喷丁增加后中扣带皮层（pMCC，参与对奖励刺激的反应抑制的区域）中对视觉大麻线索的激活。临床结局的探索性评价进一步发现，在服用加巴喷丁与安慰剂的参与者中：1）dACC GABA水平升高与较低的躁狂/混合和抑郁症状相关，2）rBG谷氨酸水平升高和对大麻线索的pMCC激活与较低的大麻使用相关。虽然有希望，但由于观察到的随机化顺序对dACC谷氨酸水平的影响，以及随机化顺序不同的统计调节因子的识别（即，吸烟状态对rBG谷氨酸水平和pMCC线索激活的影响）。尽管如此，他们提供了必要的基础，更稳健的设计（瓮随机，平行组）的未来研究辅助加巴喷丁BD+CUD。
Disrupted brain gamma-Aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200mg/day) in BD+CUD (n=22). Primary analyses revealed that, A) gabapentin was well-tolerated, adherence and retention were high, B) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels, and C) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that, in participants taking gabapentin versus placebo: 1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and 2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels, and identification of statistical moderators that differed by randomization order (i.e., cigarette-smoking status on rBG glutamate levels and pMCC cue-activation). Nonetheless, they provide the necessary foundation for a more robustly-designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD+CUD.
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DOI：
10.1038/npp.2017.198
发表时间：
2018-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Hasin DS
通讯作者：
Hasin DS
影响因子：
3.4
作者：
de Guglielmo, Giordano;Cippitelli, Andrea;Ciccocioppo, Roberto
通讯作者：
Ciccocioppo, Roberto
影响因子：
3.4
作者：
Cousijn, Janna;Goudriaan, Anna E.;Wiers, Reinout W.
通讯作者：
Wiers, Reinout W.
影响因子：
3.4
作者：
Aracil-Fernandez, Auxiliadora;Almela, Pilar;Manzanares, Jorge
通讯作者：
Manzanares, Jorge
影响因子：
4.4
作者：
Edden, Richard A. E.;Puts, Nicolaas A. J.;Harris, Ashley D.;Barker, Peter B.;Evans, C. John
通讯作者：
Evans, C. John