Amphetamines 安非他明[苯丙胺，解除忧郁、疲劳的药] Amphetamine Psychosis. There are probably no other toxic substances which are as frequently linked with paranoid manifestations as the amphetamines. It has been well known for some years now that high doses or chronic use of them (or even in some cases as small an amount as 50 mg of dextroamphetamine) can produce a psychotic state with marked paranoid characteristics. Early reports had presumed that the action of amphetamines was to induce "a state of distractible alertness, facilitate feelings of personal reference from the environment, and thus precipitate paranoid episodes in emotionally predisposed persons; whether the episode is transitory or becomes chronic would depend on the severity of the pre-psychotic tendency toward paranoid, projective processes" (Chapman,1954). More recent studies, however, have emphasized more specifically pharmacological effects. As in the case in all of these toxic states, the actual situation is more complex and involves the interactions between personality and contextual and drug effects. 安非他明精神病。 可能没有其他有毒物质像安非他明那样经常与妄想症表现相联系。多年来，人们已经清楚地知道，高剂量或长期使用它们（甚至在某些情况下，小到50毫克右旋安非他明的量）就可以产生一种具有明显偏执特征的精神病状态。早期的报告曾推测安非他明的作用是诱发 "一种可分心的警觉状态，促进来自环境的个人参照感，从而诱发情绪易感者的偏执发作；这种发作是暂时性的还是变成慢性的，将取决于精神病前偏执、投射过程倾向的严重程度"（Chapman,1954）。然而，最近的研究则更具体地强调了药理作用。如同所有这些中毒状态的情况一样，实际情况更为复杂，涉及到人格、环境性和药物效应之间的相互作用。 The psychosis produced by acute or chronic abuse of amphetamines—as a toxic effect—has a relatively characteristic and predictable pattern which is much like paranoid schizophrenia (Rylander, 1972). Opinion is divided, as might be expected, as to the extent to which the toxic psychosis serves as a model psychosis for paranoid schizophrenia—but there is no question that the similarity is strong. Amphetamine psychotics are often delusional, and suffer from tactile hallucinations similar to those observed in cocaine psychosis—a form of hallucinatory parasitosis or formication. Amphetamine psychotics are often fascinated with tiny details of objects in their environment, and often spend hours contemplating some trivial thing. 急性或慢性滥用安非他明（作为一种毒性效应）所产生的精神病，具有相对的特征和可预测的模式，这很像偏执型精神分裂症（Rylander，1972）。正如可能预期的那样，至于中毒性精神病在多大程度上可以作为偏执型精神分裂症的模型精神病，意见有分歧——但毫无疑问，这种相似性是很强的。安非他命精神病患者通常有妄想，并且患有类似于可卡因精神病中所观察到的触觉幻觉——这是一种幻觉性寄生症或蚁走感。安非他明精神病人往往对环境中物体的微小细节着迷，经常花几个小时沉思一些琐碎的事情。 In Ellinwood's study (1969) on the influence of amphetamines on cats, he observed compulsive grooming reminiscent of the delusional parasitosis, compulsive sniffing of a tiny area, often for hours at a time, and hyperattentiveness to movements and sounds in the environment. Aggressive cats tended to show hyperaggressivity under the influence of the drugs, while less aggressive cats showed an increase of fear and suspicious behavior. Ellinwood speculates that the intoxication with amphetamines stimulates the CNS components, which produce attending responses with subsequent emotional arousal when they are electrically stimulated. Thus stimulation of the amygdalae in normal animals produces many of the same type of responses as are observed under the influence of amphetamines. The amphetamine brings on a spiking activity in the amygdalae and results in catecholamine depletion. Similar effects are seen in the mesencephalic reticular activating system and in areas of the brain stem which coordinate eye movements with postural and vestibular mechanisms. Also it seems that the temporal cortex and the anterior limbic systems are involved. The activation of these areas may be related to the heightening and distortion of emotional interpretation of current experience and memory contents. 在Ellinwood关于安非他明对猫的影响的研究中（1969年），他观察到了让人联想到妄想性寄生虫病的强迫性梳理、对一个微小区域的强迫性嗅闻，往往一闻就是几个小时，以及对环境中的动作和声音的过度敏感。攻击性强的猫在药物的影响下往往表现出超强的攻击性，而攻击性较弱的猫则表现出恐惧和可疑行为的增加。Ellinwood推测，安非他明的中毒刺激了中枢神经系统的组件，当它们受到电刺激时，会产生反应[attending怎么翻译？]，随后产生情绪兴奋。此，刺激正常动物的杏仁核会产生许多与在安非他明影响下观察到的相同类型的反应。安非他明在杏仁核中带来了尖峰活动，导致儿茶酚胺的消耗。类似的影响也出现在间脑网状激活系统和脑干中协调眼球运动与姿势和前庭机制的区域。此外，颞叶皮层和前边缘系统似乎也参与其中。这些区域的激活可能与对当前经验和记忆内容的情感解释的强化和扭曲有关。 A later study by the same author (Ellinwood,1971) indicates the relationship between amphetamine-induced paranoid states and homicidal acts. The causality is not linear, but must be taken in the context of predisposing personality factors and environmental circumstances which trigger the outbreak of violence. The use of amphetamines produces a paranoid state in which the increased suspiciousness and delusional distortion are accompanied by intense fear and panic, and a tendency to impulsive behavior. In this context an environmental stimulus which is misinterpreted—a relatively minor incident, perhaps—can act as a stimulus to violent response. In most of these cases, due to the suspiciousness and fear of attack, the patients at the time of the homicidal attempt were carrying a concealed weapon. The relationship of paranoid states to a tendency toward violent and often homicidal or suicidal behavior presents a serious consideration in the broad context of the increased availability and use of amphetamines. 同一作者后来进行的一项研究(Ellinwood，1971年)表明，安非他明引起的偏执状态与杀人行为之间存在着关系。这种因果关系不是线性的，必须结合引发暴力事件的诱发性人格因素和环境条件来看待。使用安非他明会产生一种偏执状态，在这种状态下，疑心病的增加和妄想的扭曲伴随着强烈的恐惧和惊慌，并有冲动行为的倾向。在这种情况下，一个被误解的环境刺激——也许是一个相对较小的事件——可以作为暴力反应的刺激。在这些案例中，由于对攻击的怀疑和恐惧，大多数患者在意图杀人时都藏有凶器。偏执状态 与 暴力倾向和往往是杀人或自杀行为 的关系，是在安非他明的供应和使用增加的大背景下的一个严重问题。 It is likely that the amphetamine psychosis is very closely associated with paranoid psychosis. In any case the differentiation is difficult. The clinical cases that are available are often complicated by the use of other drugs and alcohol. Patients who develop amphetamine psychosis may show a preschizoid or preschizophrenic pattern of character pathology prior to the development of the psychosis, but they frequently show lack of any family history of schizophrenia, and the psychotic episode is usually of brief duration. They often also do not show the characteristic looseness of associations or deficit in reality testing which is so characteristic of the schizophrenic population (Lynn,1971). 安非他明精神病很可能与偏执型精神病有非常密切的联系。在任何情况下，区分都是困难的。现有的临床病例往往因使用其他药物和酒精而变得复杂。患安非他明精神病的患者在精神病发生之前，可能表现出一种类前分裂型或前精神分裂症的性格病理模式，但他们经常表现出缺乏任何精神分裂症的家族史，而且精神病发作的时间通常很短。他们往往也不表现出精神分裂症患者特有的联想松散或现实检验的缺陷（Lynn，1971）。 Clinical Studies. However, under experimental conditions, it is not difficult to produce the amphetamine psychosis. In the study reported by Griffith et al.(1972), psychosis developed in eight out of nine subjects under the administration of amphetamines, although the nine subjects were individuals with previous experience of self-administered amphetamine. The subjects became quite depressed, then hypochondriacal, irritable, fault-finding, and anorexic. In this particular study, predrug personality did not seem to be an important variable, since the subjects were not considered to be psychotic, or even borderline. The authors regard the effects as due to the psychotomimetic properties of the drug itself. They propose that the psychotic effects may be due to depletion of CNS catecholamine stores as a pharmacological effect of dextroamphetamine or one of its metabolites. 临床研究。 然而，在实验条件下，产生安非他明精神病并不困难。在Griffith等人(1972)报道的研究中，9名受试者中，有8名受试者在服用安非他明后出现了精神病，尽管这9名受试者都是以前有自服安非他明经验的人。这些受试者变得相当抑郁，然后是疑病症、易怒、挑剔和厌食。在这项特殊的研究中，吸毒前的人格似乎并不是一个重要的变量，因为受试者不被认为是精神病患者，甚至是边缘型的。作者认为这些影响是由于药物本身的致幻特性造成的。他们认为，精神病性效应可能是由于右旋安非他明或其代谢物之一的药理效应导致中枢神经系统儿茶酚胺储存耗尽所致。 The abuse of amphetamines usually begins with oral ingestion, but the amount ingested must be rapidly increased due to the rapid buildup of tolerance to the drug effect. Many amphetamine users then turn to the intravenous use of the drug at increasingly high levels. Sooner or later, paranoid symptoms inevitably develop. Kramer et al.(1967) report in their group of amphetamine abusers that the delusional quality of the experiences in the toxic psychosis was available to the evaluation of the subjects. They would feel, for example, that strangers were watching them, that their friends had been informing on them, that their apartments were bugged by the police, or that shadows and trees in the street were actually disguised detectives, etc. But these persecutory fantasies and illusions were always recognized as delusional. The subjects knew that their feelings and thoughts were paranoid, but apparently were not seriously disturbed by it—often making a game out of the feelings. 滥用安非他明通常是从口服开始的，但由于对药物效应的耐受性迅速增强，必须迅速增加摄入量。许多安非他明使用者便转而采用静脉注射的方式，且注射量越来越高。迟早会不可避免地出现偏执症状。Kramer等(1967)在他们的一组安非他明滥用者的报告中指出，中毒性精神病中的经验的妄想性质量是可以用来评价受试者的。例如，他们会觉得有陌生人在监视他们，他们的朋友一直在向他们告密，他们的公寓被警察窃听，或者街上的影子和树木实际上是伪装的侦探，等等。但这些迫害性的幻想和幻觉总是被人们认定为妄想。受试者知道自己的感觉和想法是偏执的，但显然并没有受到严重的困扰——往往把这种感觉当成游戏。 Gradually very high tolerance levels are developed so that commercial preparations of amphetamines are unable to produce any effect. The sudden withdrawal of the drug often unmasks a degree of chronic fatigue that is built up over the sleepless days that have preceded. Often subjects are plunged into an intense depression which may be suicidal in its intensity. There is a distant abstinence syndrome which is associated with this pattern of withdrawal. The authors underlined the addictive potential of the use of amphetamines. The addictive potential is an aspect of the use of amphetamines that has only recently come into appreciation (Grinspoon and Hedblom,1972). 逐渐形成非常高的耐受性，以至于安非他明的商业制剂无法产生任何效果。突然停药往往会暴露出一定程度的慢性疲劳，这种疲劳是在之前的不眠之夜积累起来的。受试者往往陷入强烈的抑郁之中，其强度可能是自杀性的。有一种远期戒断综合征，与这种戒断模式有关。作者强调了使用安非他明的成瘾性。成瘾的可能性是安非他明使用的一个方面，只是最近才得到重视（Grinspoon和Hedblom，1972年）。 Amphetamines as a family of drugs have been used for some years now for a variety of medical conditions. These conditions include the treatment of narcolepsy, the control of hyperkinetic behavioral disorders in children, the relief of fatigue and deterioration in psychomotor performance, the treatment of mild depression, appetite control, and for counteracting fatigue in persons who are required to perform tasks requiring strong mental or physical application over long periods of time. There is little question that the potential for abuse in such usages is great, particularly when it is appreciated that the effectiveness of amphetamines in a number of these more general usages is not very high. Self-medication is a particular danger in the use of these drugs (Committee on Alcoholism and Addiction,1966). 安非他明作为一种药物系列，多年来一直用于治疗各种病症。这些病症包括治疗嗜睡症、控制 儿童的亢进性行为障碍、缓解疲劳和精神运动表现的恶化、治疗轻度抑郁症、控制食欲，以及对付需要长期从事需要强烈的精神或体力应用的工作的人的疲劳。毫无疑问，在这些用途中，滥用的可能性很大，特别是当我们认识到安非他明在许多这些较一般用途中的效力并不高时。自我治疗是使用这些药物的一个特殊危险（酒精中毒和成瘾问题委员会，1966年）。 In addition to the more common psychotic paranoid state produced as a toxic effect of the amphetamines, there has also been described an amphetamine abstinence psychosis, which is the most terrifying and dramatic sequel to withdrawal of the drug after it has been used more or less chronically at toxic levels. Rather than seeming a toxic effect, it appears to be functional psychosis precipitated by amphetamine withdrawal. There is an interval between the stopping of amphetamine use and the onset of psychotic symptoms which may last a variable length of time, from a few days to as long as two months. The dependence on the drug is apparently physical and affects a number of body systems, particularly the suppression of REM sleep. After withdrawal of the drug there is a marked rebound and overcompensation in REM time, as well as a decrease in REM latency. Similar suppression and rebound phenomena of REM sleep have been observed in cases of other drugs of high addictive potential, such as heroin, morphine, alcohol, barbiturates etc. It has even been suggested that delirium tremens following prolonged alcohol consumption may represent a state of acute REM rebound from a chemically induced REM deprivation (Greenberg and Pearlman,1967). Also Connel (1958) has suggested certain parallels between amphetamine addiction and alcoholism. 除了比较常见的作为安非他明毒性作用产生的精神病性偏执状态外，还有人描述了一种安非他明戒断性精神病，它是在长期或多或少地使用安非他明达到毒性水平后，戒断药物后最可怕、最戏剧性的后遗症。与其说它看起来是一种毒害作用，不如说它是由安非他明戒断引发的功能性精神病。从停止使用安非他明到出现精神病性症状之间有一段间隔，这段间隔时间长短不一，从几天到两个月不等。对药物的依赖性显然是生理性的，会影响身体的一些系统，特别是对REM睡眠的抑制。停药后REM时间有明显的反弹和过度补偿，REM潜伏期也有减少。在其他具有高成瘾性的药物，如海洛因、吗啡、酒精、巴比妥类药物等情况下，也观察到REM睡眠的类似抑制和反弹现象。甚至有人认为，长期饮酒后的震颤谵妄可能代表了化学诱导的REM剥夺后的急性REM反弹状态（Greenberg和Pearlman，1967）。此外，Connel（1958年）还提出了安非他明成瘾和酒精中毒之间的某些相似之处。 Recently the utility of amphetamine-induced psychosis as an experimental model for paranoid states has been carefully reviewed, and the data which emphasized similarities as well as the differences between amphetamine-induced psychosis and the clinically familiar and paranoids chizophrenia have been summarized by Snyder (1972, 1973). He quotes the Griffith et al. (1970, 1972) study in which a paranoidlike psychosis was induced by the administration of amphetamines in subjects without any prior history of amphetamine psychosis or any indication of schizoid or schizophrenic tendencies. The psychosis produced resembles paranoid schizophrenia and includes a number of behavioral effects such as hyper-vigilance, sleeplessness, and stereotypical behavior. Because of the subtlety and frequent difficulty of eliciting paranoid mechanisms, it would not seem that the possibility of predrug paranoid traits has been completely eliminated, even in these subjects. 最近，Snyder(1972，1973)对安非他明诱发的精神病作为偏执状态的实验模型的效用进行了仔细的审查，并对那些 强调 安非他明诱发的精神病 与 临床上熟悉的偏执性的精神分裂症之间 的相似性和差异性的数据 进行了总结。他引用Griffith等(1970，1972)的研究，在此前没有任何安非他明精神病史 或 任何分裂型或精神分裂倾向迹象 的受试者中，通过服用安非他明诱发了偏执样精神病。所产生的精神病与偏执型精神分裂症相似，并包括一些行为上的影响，如过度警惕、失眠、刻板行为等。由于诱发偏执机制的微妙性和经常性的困难，即使在这些受试者中，似乎也没有完全消除药物前偏执特征的可能性。 Mechanisms. In any case—despite the obvious discrimination between the amphetamine psychosis and the paranoid psychosis—the effects of the drug seem to be unequivocal. The extent to which paranoid trends are embedded in the preexisting personality structure remains a moot question; but there is no question that the amphetamine effect is clearly in the direction of either exacerbating or producing paranoid tendencies. Both the amphetamine psychosis and the cocaine psychosis, both of which are produced by mechanisms which apparently involve the metabolism of brain catecholamines, provide the clearest models of drug-induced paranoid states (Ellinwood et al.,1973). Snyder discusses the differential effects of the amphetamines on catecholamine pathways, particularly those dealing with dopamine and norepinephrine. The more schizophrenic manifestations seem to be related to the effect on dopamine mediating tracts, while the more paranoid manifestations may relate to the norepinephrine mediated systems which relate to alerting mechanisms. Snyder writes: 机制. 在任何情况下——尽管安非他明精神病和偏执型精神病之间存在明显的区别——药物的影响似乎是明确的。偏执趋势在多大程度上被嵌入到已有的人格结构中，仍然是一个不确定的问题；但毫无疑问，安非他明的作用显然是朝着加重或产生偏执倾向的方向发展的。安非他明精神病和可卡因精神病，都是由明显涉及脑儿茶酚胺代谢的机制产生的，它们提供了药物诱导的偏执状态的最清晰的模型（Ellinwood et al.,1973）。Snyder讨论了安非他明类药物对儿茶酚胺通路的不同影响，特别是那些处理多巴胺和去甲肾上腺素的通路[多巴胺是一种内源性儿茶酚胺，且是去甲肾上腺素的前体，有直接或间接（通过释放去甲肾上腺素）兴奋多巴胺能受体和β1 -及α1-肾上腺素能受体的作用。]。更多的精神分裂症表现似乎与对多巴胺介导道的影响有关，而更多的偏执表现可能与去甲肾上腺素介导的系统有关，这些系统与警戒机制有关。Snyder写道。 Besides their psychotogenic effects, amphetamines produce a wide spectrum of other effects. Perhaps, were amphetamines to act solely on selected dopamine tracts, the psychosis they precipitate would be a more faithful model of an undifferentiated form of schizophrenia or one whose characteristics were determined primarily by the previous personality of the patient. Conceivably, other amphetamine effects transform the "model schizophrenia" into a predominately paranoid psychosis. One possible candidate for a "contaminating" action would be the nonrepinephrine-mediated alerting effect of amphetamines. One might speculate that this alerting action forces the patient to strive for an intellectual framework in which to focus all the strange feelings that are coming over him as the psychosis develops (1972, p.177). 除了精神作用外，安非他明还会产生广泛的其他作用。也许，如果安非他明只对选定的多巴胺道起作用，它们所引发的精神病将是一种未分化形式的精神分裂症的更忠实的模型，或者其特征主要由病人以前的人格决定。可以想象，其他安非他明的作用会使 "模型精神分裂症 "转变为一种主要是偏执型的精神病。一个可能的 "污染 "作用的候选者是安非他明的非肾上腺素介导的警觉作用。人们可以推测，这种警戒作用迫使病人努力寻找一个智力框架，以集中处理随着精神病的发展而出现的所有奇怪的感觉（1972年，第177页）。 The process of establishing meaning and discovering it in a system of delusions is what we have referred to equivalently as the "paranoid construction." 在妄想系统中建立意义和发现意义的过程，就是我们所说的等价的 "偏执建构"。 The paranoid construction together with the state of alertness and hypervigilance may be mediated by norepinephrine systems and may also facilitate preexisting trends in the personality. It is also possible with these patients that the paranoid dynamics may serve a protective or covering action in the face of the disruptive disorganization experienced in the schizophrenic effects produced by the drug. I only wish to note in passing that the dorsal norepinephrine system, which involves inputs to the medial forebrain bundle and septum, which subsequently exercise important neurophysiological influences on central structures involved in the processing of affective and cognitive inputs—including the hippocampus and related limbic system circuits (Meissner,1966)—provides an important neurophysiological link which may also be involved in other toxic and organic states which produce paranoid manifestations. 偏执建构以及警觉和高度警惕的状态可能是由去甲肾上腺素系统调节的，也可能促进人格中预先存在的趋势。对于这些患者，也有可能在面对药物产生的精神分裂症效应中所经历的破坏性混乱时，偏执动力学可能起到保护或掩护作用。我只想顺便指出，背侧去甲肾上腺素系统涉及到前脑内侧束和隔膜的输入，随后对参与处理情感和认知输入的中枢结构——包括海马和相关的边缘系统回路(Meissner,1966)——施加重要的神经生理影响提供了一个重要的神经生理联系，这个联系也可能参与到产生偏执表现的其他毒性和有机状态中。