Sunnybrook Research Institute, Division of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Clinical Laboratory and Diagnostic Services, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Brain. 2019 Sep 1;142(9):2800-2812. doi: 10.1093/brain/awz213.
Cognitive dysfunction affects 40-80% of patients with multiple sclerosis. Smoking cannabis may add to these deficits. It is unclear whether coming off cannabis results in cognitive improvement. To address this question, 40 patients with multiple sclerosis who started using cannabis after the onset of multiple sclerosis and who used it for at least 4 days a week over many years were divided by odd-even number selection into two groups: cannabis continuation and cannabis withdrawal. Assessments took place at baseline and after 28 days and included serial versions of the Brief Repeatable Neuropsychological Battery for multiple sclerosis containing tests of verbal and visual memory, processing speed and executive function; structural and functional MRI, the latter entailing a compatible version of the Symbol Digit Modalities Test; urine for cannabinoid metabolites to detect compliance with abstinence. Only those participants deemed globally impaired at baseline (failure on at least two cognitive domains) were enrolled. The results revealed that the two groups were well matched demographically and neurologically. One subject was removed from the withdrawal group because of failed abstinence. Urine analysis revealed the cannabinoid consumed was predominantly tetrahydrocannabinol (THC). There were no baseline between group cognitive differences, but by Day 28 the withdrawal group performed significantly better on every cognitive index (P < 0.0001 for all). Significant within group differences were present for every test over time, but only in the abstinent group (P < 0.0001 for all tests). There were no between group baseline or Day 28 differences in structural MRI indices (global atrophy, total T1 and T2 lesion volume). At index assessment the two groups had a similar performance on the functional MRI-compatible Symbol Digit Modalities Test and there were no group differences in brain activation. However, by Day 28, the withdrawal group completed more trials correctly (P < 0.012) and had a faster reaction time (P < 0.002), associated with significantly increased activation in brain regions known to be associated with performance of the test (bilateral inferior frontal gyri, caudate and declive/cerebellum, P < 0.001 for all regions). These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed and executive function after 28 days of drug abstinence. The absence of similar improvements in a matched multiple sclerosis group that remained on cannabis shows that beneficial cognitive change after stopping cannabis is not solely attributable to the effects of practice.
认知功能障碍影响 40-80%的多发性硬化症患者。吸烟大麻可能会加剧这些缺陷。目前尚不清楚戒除大麻是否会导致认知能力的改善。为了解决这个问题，将 40 名多发性硬化症患者随机分为两组：大麻继续使用组和大麻戒断组。这些患者在多发性硬化症发作后开始使用大麻，并且每周至少使用大麻 4 天，使用时间超过多年。评估在基线和 28 天后进行，包括多发性硬化症简短重复神经心理测试电池的系列版本，其中包含言语和视觉记忆、处理速度和执行功能测试；结构和功能磁共振成像，后者需要兼容符号数字模态测试；尿液中大麻素代谢物的检测以检测是否遵守禁欲。只有那些在基线时被认为整体受损（至少两个认知领域失败）的参与者被纳入。结果表明，两组在人口统计学和神经学方面匹配良好。一名退出者因未能戒断而被从戒断组中删除。尿液分析显示消耗的大麻素主要为四氢大麻酚（THC）。两组在基线时没有认知差异，但到第 28 天，戒断组在每个认知指标上的表现都明显更好（所有指标 P < 0.0001）。随着时间的推移，每个测试都存在组内差异，但仅在禁欲组中存在（所有测试 P < 0.0001）。两组在结构磁共振成像指数（整体萎缩、总 T1 和 T2 病变体积）上没有基线或第 28 天的差异。在指数评估时，两组在功能磁共振成像兼容符号数字模态测试中的表现相似，并且大脑激活没有组间差异。然而，到第 28 天，戒断组正确完成的试验次数更多（P < 0.012），反应时间更快（P < 0.002），与与测试表现相关的大脑区域的激活显著增加相关（双侧额下回、尾状核和小脑下降/小脑，所有区域 P < 0.001）。这些结果表明，多发性硬化症患者如果经常、长期使用大麻，在戒断大麻 28 天后，记忆力、处理速度和执行功能会有显著改善。在匹配的多发性硬化症组中，仍在使用大麻的患者没有类似的改善，这表明停止使用大麻后认知能力的有益变化不仅仅归因于练习的影响。
