Wolff Valérie, Jouanjus Emilie
Stroke Unit, Strasbourg University Hospital, 1, avenue Molière, 67098 Strasbourg, France; EA3072, Federation of Translational Medicine of Strasbourg, University of Strasbourg, Strasbourg, France.
Pharmacoepidemiology Team, UMR1027-University of Toulouse, Toulouse, France; CEIP-Addictovigilance, Department of Medical and Clinical Pharmacology, Toulouse University Hospital, Toulouse, France.
Epilepsy Behav. 2017 May;70(Pt B):355-363. doi: 10.1016/j.yebeh.2017.01.031. Epub 2017 Feb 23.
It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids). The distribution by type of stroke was as follows: 4 patients with an undetermined type of stroke, 85 with an ischemic stroke and/or a transient ischemic attack, and 9 with a hemorrhagic stroke. The mean age of patients was 32.3±11.8years (range 15-63), and the majority of them were male with a sex ratio of 3.7:1. Cannabis was often smoked with tobacco in 66% of cases. Most of the patients with cannabinoids-related strokes were chronic cannabis users in 81% of cases, and for 18% of them, there was a recent increase of the amount of cannabis consumption during the days before the occurrence of stroke. Even if the prognosis of stroke was globally favorable in 46% of cases, with no or few sequelae, 5 patients died after the neurovascular event. One striking element reported in the majority of the reports was a temporal relationship between cannabinoids use, whether natural or synthetic, and the occurrence of stroke. However, a temporal correlation does not mean causation, and other factors may be involved. Cannabis may be considered as a risk factor of stroke until research shows evidence of an underlying mechanism that, alone or in association with others, contributes to the development of stroke. As of today, reversible cerebral vasoconstriction triggered by cannabinoids use may be a convincing mechanism of stroke in 27% of cases. Indeed, despite the widespread use of cannabinoids, the low frequency of neurovascular complications after their use may be due to a genetic predisposition to their neurovascular toxicity in some individuals. Further studies should focus on this point. More importantly however, this low frequency may be underestimated because the drug consumption may not be systematically researched, neither by questioning nor by laboratory screening. Besides this vascular role of cannabinoids in the occurrence of stroke, a cellular effect of cannabis on brain mitochondria was recently suggested in an experimental study. One of the mechanisms involved in young cannabis users with stroke may be the generation of reactive oxygen species leading to an oxidative stress, which is a known mechanism in stroke in humans. It is useful to inform the young population about the real potential risk of using cannabinoids. We suggest to systematically ask all young adults with stroke about their drug consumption including cannabinoids, to screen urine for cannabis or to include a specific diagnostic test to detect synthetic cannabinoids, and to obtain non-invasive intracranial arterial investigations (i.e. CT-angiography or cerebral MRA) in order to search for cerebral vasoconstriction. However, several questions remained unresolved and further research is still needed to assess the pathophysiological mechanisms involved in young cannabinoids users with stroke. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy".
识别所有可能导致近期年轻人群中风发病率上升的因素至关重要。鉴于大麻素(大麻和合成大麻素)在全球范围内的使用情况、近期一些国家对其消费的合法化以及它们被认为与心血管事件有关,我们评估了它们在年轻人神经血管并发症发生中的作用。文献中描述了98例与大麻素相关的中风患者(85例在使用大麻后发病,13例在使用合成大麻素后发病)。中风类型分布如下:4例中风类型未确定,85例为缺血性中风和/或短暂性脑缺血发作,9例为出血性中风。患者的平均年龄为32.3±11.8岁(范围15 - 63岁),其中大多数为男性,男女比例为3.7:1。66%的病例中,大麻常与烟草一起吸食。81%与大麻素相关中风的患者为慢性大麻使用者,其中18%的患者在中风发生前几天近期大麻消费量有所增加。即使46%的病例中风预后总体良好,无或仅有轻微后遗症,但仍有5例患者在神经血管事件后死亡。大多数报告中提到的一个显著因素是,无论使用天然还是合成大麻素,其使用与中风发生之间存在时间关系。然而,时间相关性并不意味着因果关系,可能还涉及其他因素。在有研究表明存在单独或与其他因素共同导致中风发生的潜在机制之前,大麻可被视为中风的一个风险因素。截至目前,在27%的病例中,大麻素使用引发的可逆性脑血管收缩可能是中风的一个有说服力的机制。事实上,尽管大麻素广泛使用,但使用后神经血管并发症发生率较低可能是由于某些个体对其神经血管毒性存在遗传易感性。进一步的研究应聚焦于此。然而,更重要地是,这种低发生率可能被低估了,因为药物消费情况可能未通过询问或实验室筛查进行系统研究。除了大麻素在中风发生中的血管作用外,一项实验研究最近提出大麻对脑线粒体有细胞效应。年轻大麻使用者中风所涉及的机制之一可能是活性氧的产生导致氧化应激,这是人类中风中一种已知的机制。告知年轻人群使用大麻素的真正潜在风险是有益的。我们建议系统地询问所有中风的年轻成年人关于他们的药物消费情况,包括大麻素,对尿液进行大麻筛查或进行特定诊断测试以检测合成大麻素,并进行非侵入性颅内动脉检查(即CT血管造影或脑MRA)以寻找脑血管收缩情况。然而,几个问题仍未解决,仍需要进一步研究来评估年轻大麻素使用者中风所涉及的病理生理机制。本文是名为“大麻素与癫痫”的特刊的一部分。