Murillo-Rodriguez Eric, Pastrana-Trejo Jose Carlos, Salas-Crisóstomo Mireille, de-la-Cruz Miriel
Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Carretera Mérida-Progreso Km. 15.5, A.P. 96 Cordemex C.P. 97310, Mérida, Yucatán, Mexico.
Grupo de Investigación en Envejecimiento, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico.
CNS Neurol Disord Drug Targets. 2017;16(4):370-379. doi: 10.2174/1871527316666170223161908.
BACKGROUND & OBJECTIVE: Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is Δ9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors. These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC. The cannabinoid receptors have been described in rat, human and mouse brains and they have been named the CB1 and CB2 cannabinoid receptors. Later, an endogenous molecule that exerts pharmacological effects similar to those described by Δ9-THC and binds to the cannabinoid receptors was discovered. This molecule, named anandamide, was the first of five endogenous cannabinoid receptor agonists described to date in the mammalian brain and other tissues. Of these endogenous cannabinoids or endocannabinoids, the most thoroughly investigated to date have been anandamide and 2-arachidonoylglycerol (2-AG). Over the years, a significant number of articles have been published in the field of endogenous cannabinoids, suggesting a modulatory profile in multiple neurobiological roles of endocannabinoids. The general consensus accepts that the endogenous cannabinoid system includes natural ligands (such as anandamide and 2- AG), receptors (CB1 and CB2), and the main enzymes responsible for the hydrolysis of anandamide and 2-AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) as well as the anandamide membrane transporter (AMT). To date, diverse pieces of evidence have shown that the endocannabinoid system controls multiple functions such as feeding, pain, learning and memory and has been linked with various disturbances, such as Parkinson´s disease. Among the modulatory properties of the endocannabinoid system, current data indicate that the sleep-wake cycle is under the influence of endocannabinoids since the blocking of the CB1 cannabinoid receptor or the pharmacological inhibition of FAAH activity promotes wakefulness, whereas the obstruction of AMT function enhances sleep. However, no solid evidence is available regarding the role of the endocannabinoid system in an unquestionable emotional component of the sleep: Dream activity. Since dreaming is a mental activity that occurs during sleep (characterized by emotions, sensory perceptions, and bizarre components) and the endocannabinoid system modulates neurobiological processes involving consciousness, such as learning and memory, attention, pain perception, emotions and sleep, it is acceptable to hypothesize that the endocannabinoid system might be modulating dream activity. In this regard, an accumulative body of evidence in human and animal models has been reported regarding the role of the endocannabinoid system in the control of emotional states and dreams. Moreover, preliminary studies in humans have indicated that treatment with cannabinoids may decrease post-traumatic stress disorder symptoms, including nightmares.
Thus, based on a review of the literature available in PubMed, this article hypothesizes a conceptual framework within which the endocannabinoid system might influence the generation of dream experiences.
大麻素是一类衍生物,包括天然存在于植物大麻中的化合物或这些分子的合成类似物。最早且研究最广泛的大麻素是Δ9-四氢大麻酚(Δ9-THC),它是大麻的主要精神活性成分,能与大麻素受体发生显著结合。这些大麻素受体是七跨膜受体,因其对包括Δ9-THC在内的大麻素化合物有反应而得名。大麻素受体已在大鼠、人类和小鼠大脑中被描述,并被命名为CB1和CB2大麻素受体。后来,人们发现了一种内源性分子,它具有与Δ9-THC相似的药理作用,并能与大麻素受体结合。这种名为花生四烯乙醇胺的分子是迄今为止在哺乳动物大脑和其他组织中描述的五种内源性大麻素受体激动剂中的第一种。在这些内源性大麻素或内源性大麻素中,迄今为止研究最深入的是花生四烯乙醇胺和2-花生四烯酸甘油酯(2-AG)。多年来,内源性大麻素领域发表了大量文章,表明内源性大麻素在多种神经生物学作用中具有调节作用。普遍的共识是,内源性大麻素系统包括天然配体(如花生四烯乙醇胺和2-AG)、受体(CB1和CB2)、负责花生四烯乙醇胺和2-AG水解的主要酶(分别为脂肪酸酰胺水解酶[FAAH]和单酰甘油脂肪酶[MAGL])以及花生四烯乙醇胺膜转运体(AMT)。迄今为止,各种证据表明,内源性大麻素系统控制着进食、疼痛、学习和记忆等多种功能,并与帕金森病等各种紊乱有关。在内源性大麻素系统的调节特性中,目前的数据表明,睡眠-觉醒周期受内源性大麻素的影响,因为阻断CB1大麻素受体或对FAAH活性进行药理抑制会促进觉醒,而阻碍AMT功能则会增强睡眠。然而,关于内源性大麻素系统在睡眠中一个无可争议的情感成分:梦境活动中的作用,尚无确凿证据。由于做梦是一种在睡眠期间发生的心理活动(其特征为情感、感官知觉和奇异成分),而内源性大麻素系统调节涉及意识的神经生物学过程,如学习和记忆、注意力、疼痛感知、情感和睡眠,因此可以假设内源性大麻素系统可能在调节梦境活动。在这方面,已有关于内源性大麻素系统在控制情绪状态和梦境方面作用的人类和动物模型的累积证据报道。此外,对人类的初步研究表明,使用大麻素治疗可能会减轻创伤后应激障碍症状,包括噩梦。
因此,基于对PubMed上现有文献的综述,本文提出了一个概念框架,在内源性大麻素系统可能影响梦境体验的产生。