Adderall, Stimulants & Modafinil for ADHD: Short- & Long-Term Effects

Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.

欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。

I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.

我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。

Today, we're discussing stimulants, in particular, stimulants for the treatment of ADHD or attention deficit hyperactivity disorder.

今天，我们讨论兴奋剂，特别是用于治疗多动症或注意力缺陷多动障碍的兴奋剂。

As many of you know, there is tremendous interest in drugs like Adderall, Ritalin, Vyvanse, and other stimulants, as well as non-stimulant prescription drugs that have been shown to improve the symptoms of ADHD, such as modafinil, armodafinil, and guanfacine.

正如许多人所知，人们对阿得拉、利他林、Vyvanse 和其他兴奋剂等药物以及已被证明可以改善多动症症状的非兴奋剂处方药（如莫达非尼、阿莫达非尼和胍法辛）有着极大的兴趣。

Today, I'm going to discuss all of these compounds in the context of how they work to improve the symptoms of ADHD.

今天，我将讨论所有这些化合物如何改善多动症的症状。

I'm going to address common questions about these compounds, such as are they just speed?

我将解决有关这些化合物的常见问题，例如它们只是速度吗？

Are they similar to meth or methamphetamine?

它们与冰毒或甲基苯丙胺相似吗？

I'll talk about their addictive potential, as well as their potential to cause psychotic symptoms, both in the short and long term.

我将讨论它们的成瘾潜力，以及它们在短期和长期内引起精神病症状的潜力。

And of course, I will talk about the scientific literature surrounding the most frequently asked question about these compounds, which is what are the long-term consequences of taking any of them in childhood or in adulthood?

当然，我将谈论围绕这些化合物最常见问题的科学文献，即在儿童或成年后服用其中任何一种会产生什么长期后果？

Now, today's discussion centers around the use of these compounds both for childhood and for adult ADHD.

现在，今天的讨论集中在这些化合物对儿童和成人多动症的使用。

But of course, I'd be remiss if I didn't acknowledge that there are a tremendous number of people that use these prescription drugs without a prescription in order to improve their ability to focus and indeed also use them recreationally.

但当然，如果我不承认有大量的人在没有处方的情况下使用这些处方药，以提高他们的注意力集中能力，而且实际上也是为了娱乐而使用它们，那就是我的失职了。

In fact, some surveys reveal that as high as 80% of college-age young adults have used one or several of prescription drugs, such as Adderall, Ritalin, Vyvanse, or similar at some point and are doing so without a prescription.

事实上，一些调查显示，高达 80% 的大学年龄的年轻人曾在某些时候使用过一种或多种处方药，例如阿得拉 (Adderall)、利他林 (Ritalin)、Vyvanse 或类似药物，并且是在没有处方的情况下使用的。

So they are either obtaining those drugs from those that do have prescriptions for them for ADHD, or they are obtaining them through black market sources, which of course carries an additional and very serious risk related to the so-called fentanyl crisis.

因此，他们要么从那些有治疗多动症处方的人那里获取这些药物，要么通过黑市来源获取这些药物，这当然会带来与所谓的芬太尼危机相关的额外且非常严重的风险。

That is as high as 75% of black market drugs nowadays of various kinds, but certainly including the sorts of drugs we're going to talk about today are contaminated with fentanyl and therefore are very deadly.

如今，黑市各种毒品中的这一比例高达 75%，但当然包括我们今天要讨论的各种毒品都被芬太尼污染，因此非常致命。

So today I'm going to describe what these various drugs really are, how they work at the level of neurons and brain networks, and how they change those brain networks in ways that really can allow people with ADHD to be able to focus better.

所以今天我将描述这些不同的药物到底是什么，它们如何在神经元和大脑网络水平上发挥作用，以及它们如何改变这些大脑网络，从而真正让患有多动症的人能够更好地集中注意力。

I will answer the common question, which is why is it that giving children speed, because indeed, several, not all, but several of the compounds I'm going to discuss are speed.

我将回答一个常见的问题，这就是为什么要给孩子速度，因为事实上，我要讨论的几种，不是全部，但有几种化合物是速度。

They are amphetamine.

它们是安非他命。

Why would that cause a reduction in hyperactivity if speed is a stimulant?

如果速度是一种兴奋剂，为什么会导致多动症减少呢？

So I'll answer that question for you, and I will also answer questions that are commonly asked, such as how these drugs impact things like sleep, hormone health, reproductive health, as well as what is their impact on height.

所以我会回答你这个问题，我也会回答常见的问题，比如这些药物如何影响睡眠、激素健康、生殖健康，以及它们对身高的影响。

Indeed, it was one prominent hypothesis that these ADHD meds could actually restrict the height of children.

事实上，一个重要的假设是，这些治疗多动症的药物实际上可以限制儿童的身高。

I'll tell you whether or not that's actually true or not.

我会告诉你这是否真的。

And I'll discuss the data surrounding whether or not these drugs predispose people to becoming addicts to other substances, even if people cease or continue taking the stimulants that can help them in the clinical sense for ADHD.

我将讨论有关这些药物是否会使人们对其他物质上瘾的数据，即使人们停止或继续服用在临床意义上可以帮助他们治疗多动症的兴奋剂。

Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。

It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.

然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。

In keeping with that theme, I'd like to thank the sponsors of today's podcast.

为了与这个主题保持一致，我要感谢今天播客的赞助商。

Let's talk about treatments for ADHD and why stimulant treatments, in particular, can be so effective.

让我们来谈谈多动症的治疗方法，以及为什么兴奋剂治疗尤其如此有效。

First of all, it's long been known that there are specific brain networks involved in what we call attention.

首先，人们早就知道，我们所说的注意力涉及特定的大脑网络。

Now, attention is not one thing, actually.

实际上，注意力并不是一回事。

It involves several different cognitive operations, including the suppression of noise.

它涉及几种不同的认知操作，包括抑制噪音。

That is, turning down the background chatter in our heads and turning down our attending to things outside us, like noises or visual cues that are not relevant to what we want to do.

也就是说，拒绝我们头脑中的背景噪音，并拒绝关注外界的事物，例如与我们想做的事情无关的噪音或视觉提示。

And it also involves ramping up or attending or focusing on particular things that are happening either in our immediate environment or in our head, or both.

它还涉及加强或关注或专注于我们周围环境或我们头脑中或两者兼而有之的特定事物。

So if that all sounds rather complex, indeed it is.

因此，如果这一切听起来相当复杂，那么确实如此。

It involves several different networks operating in parallel.

它涉及并行运行的多个不同网络。

But what we know for sure, based on a lot of clinical and scientific laboratory data, is that the so-called prefrontal cortex, the region of neural real estate in your brain just behind your forehead, is critically important for orchestrating which neural circuits are going to be more or less active at a given moment in order to bring about what we call focus or attention or task switching, or our ability indeed to multitask because we can actually multitask to some extent.

但根据大量的临床和科学实验室数据，我们可以肯定的是，所谓的前额叶皮层，即大脑中前额后面的神经区域，对于协调哪些神经回路在特定时刻或多或少活跃至关重要，以实现我们所说的焦点或注意力或任务切换，或者我们实际上能够同时处理多项任务的能力，因为我们实际上可以在某种程度上处理多项任务。

In fact, if you were to look at somebody and focus on perhaps their expression on their face, you could do that while also attending to a conversation that's happening nearby.

事实上，如果您要看着某人并关注他们脸上的表情，您可以同时关注附近正在发生的对话。

It's energetically demanding.

它对精力的要求很高。

It's hard to do, but we can do that.

这很难做到，但我们可以做到。

That's actually referred to as covert attention.

这实际上被称为隐性注意力。

You're covertly paying attention to something else, and then you can switch that attention back to just one thing or one small collection of things.

你正在偷偷地关注其他事情，然后你可以将注意力转移回一件事或一小部分事情上。

The point being that attention is a powerful resource.

重点是注意力是一种强大的资源。

It's what allows us to navigate through life with efficiency and to be adaptive in our behaviors.

它使我们能够高效地度过生活并适应我们的行为。

It's what allows us to learn and to build relationships and have successful school careers and professional careers, and so on.

它让我们能够学习、建立关系、拥有成功的学业和职业生涯等等。

But it is indeed expensive.

但确实很贵。

It takes metabolic resources.

它需要代谢资源。

Just at rest, if you were to think about essentially nothing or whatever just pops into your mind with no dedicated effort toward paying attention to anything, your brain would consume about 25% of your daily caloric needs.

在休息时，如果您基本上什么都不去想，或者任何突然出现在您脑海中的事情，并且没有专门努力去关注任何事情，那么您的大脑将消耗您每日热量需求的大约 25%。

And then when you lump on top of that your need or your attempts to focus on things, to pay attention to specific things It should come as no surprise as to why that often can make us feel tired, as if we've been working really hard, or we've been running a "mental marathon" when trying to learn and attend to things.

然后，当你把你的需要或你试图专注于事物、关注特定事物的努力放在首位时，这应该不足为奇，为什么这常常会让我们感到疲倦，就好像我们一直在努力工作，或者在尝试学习和关注事物时我们一直在跑“精神马拉松”。

It's hard work for the brain, and yet we can pay attention because of that very precious real estate just behind our foreheads, the prefrontal cortex.

这对大脑来说是一项艰苦的工作，但我们可以集中注意力，因为我们的额头后面有一个非常宝贵的区域，即前额皮质。

Now, in people, both children and adults, that have ADHD, their prefrontal cortex is not necessarily deficient in any specific way, except that it is not as good at orchestrating the activity of other brain networks operating in parallel with it.

现在，对于患有多动症的人，无论是儿童还是成人，他们的前额叶皮层不一定有任何特定的缺陷，只是它不擅长协调与其并行运行的其他大脑网络的活动。

What do I mean by that?

我这么说是什么意思？

Well, if we take a step back and say, what is the prefrontal cortex really doing?

好吧，如果我们退一步说，前额叶皮层到底在做什么？

The prefrontal cortex has this amazing ability, through what's called top-down inhibition, to quiet other brain areas.

前额叶皮层具有这种惊人的能力，通过所谓的自上而下的抑制，使其他大脑区域安静下来。

So for instance, if you are feeling agitated but you need to sit still, your ability to sit still, even if it takes a bit of work, is coordinated by your prefrontal cortex sending inhibitory, suppressive electrical signals to the networks of your brain that are trying to generate physical action.

举例来说，如果你感到烦躁，但你需要安静地坐着，那么你安静地坐着的能力，即使需要一些努力，也是由你的前额叶皮层向试图产生身体动作的大脑网络发送抑制性电信号来协调的。

In addition to that, if you are in a conversation that's either a difficult one or a boring one, or you are tempted to interrupt, and you are actively holding back your desire to walk away or to yawn or to blurt something out, it's your prefrontal cortex that is controlling that act of suppression.

除此之外，如果你正在进行一场困难或无聊的谈话，或者你很想打断，并且你正在积极抑制自己走开、打哈欠或脱口而出的欲望，那么正是你的前额叶皮层在控制这种抑制行为。

So in many ways, you can just think of the prefrontal cortex as an orchestra conductor that is essentially saying, "Shh," or, "Not right now.

因此，在很多方面，你可以将前额叶皮层想象成一个管弦乐队指挥，本质上是在说“嘘”，或者“现在不行。

Be quiet.

安静点。

This is not the time," to many different brain networks all at once.

现在不是时候”，同时对许多不同的大脑网络来说。

Now, in addition to that, your prefrontal cortex is coordinating with other brain networks that are involved in generating what's called salience, or attention to particular signals.

现在，除此之外，您的前额叶皮层还与其他大脑网络进行协调，这些网络参与产生所谓的显着性或对特定信号的关注。

So the prefrontal cortex, in many ways, is like a teacher or an orchestra conductor.

因此，前额叶皮层在很多方面就像一位老师或乐团指挥。

It can point to, in the neurochemical sense that is, point to a given brain structure and say, "You, I'd like to hear more from you right now.

从神经化学意义上来说，它可以指向某个特定的大脑结构并说：“你，我现在想听听你的更多信息。

Yes, you, the student in the back, speak up." And a moment later, point to a collection of small students chattering in the back, again, I'm presenting all this by analogy, and say, "Hey, hey, hey, you guys, quiet down right now.

是的，你，后面那个学生，快说吧。”过了一会儿，我又指着后面一群叽叽喳喳的小学生，说：“嘿嘿嘿，你们安静点。

So and so is going to come up to the front of the room and help us work through this particular math problem." So when we hear that the prefrontal cortex exerts what's called executive function, what that refers to is the prefrontal cortex's ability to quiet the activity of particular neural circuits and to enhance or increase the salience of other neural circuits that are involved in creating our spotlight of attention.

某某将来到房间前面帮助我们解决这个特殊的数学问题。”因此，当我们听说前额叶皮层发挥所谓的执行功能时，它指的是前额叶皮层使特定神经回路的活动安静下来并增强或增加其他神经回路的显着性的能力，这些神经回路参与创造我们的注意力。

And what we know for sure, based on many, many brain imaging studies, is that ADHD is not necessarily a deficit in prefrontal cortical function, but rather the prefrontal cortex's ability to communicate with other brain areas in the proper ways.

基于大量的脑成像研究，我们可以肯定的是，多动症不一定是前额皮质功能的缺陷，而是前额皮质以正确方式与其他大脑区域沟通的能力的缺陷。

And so what results in the brain of a person, either young or old, with ADHD, is that a lot of the background chatter becomes very, very loud.

因此，患有注意力缺陷多动症的人，无论年轻还是年长，其大脑都会导致很多背景噪音变得非常非常响亮。

So for instance, we have a brain network called the default mode network.

例如，我们有一个称为默认模式网络的大脑网络。

This is a fascinating brain network.

这是一个令人着迷的大脑网络。

This is the brain network that is active when you just sort of sit in place and don't think about much, and then you start having ideas about what you might do next week.

当你坐在原地，不去想太多的时候，这个大脑网络就会活跃起来，然后你就开始思考下周要做什么。

It tends to be very autobiographical, so you might remember an experience from the past.

它往往是非常自传性的，所以你可能会记得过去的经历。

You might think about some of your desires, some of your dislikes.

你可能会想到你的一些愿望，一些你不喜欢的东西。

This default mode network, as it's called, is also involved in our imagination, in our spooling together of different experiences that we've had.

这个所谓的默认模式网络也参与了我们的想象力，参与了我们将所拥有的不同经历交织在一起的过程。

It doesn't tend to be the thing that's really focused on anything external, in particular, all at once.

它往往不会真正关注任何外部事物，特别是同时关注的事物。

The default mode network is always active, but it's when we start to attend to something, especially things external to us, like something written on a page or a conversation or something that we really need to learn, something we need to pay attention to, that the activity of the default mode network is suppressed somewhat.

默认模式网络总是活跃的，但当我们开始关注某些事情时，尤其是我们外部的事情，比如写在页面上的东西或对话或我们真正需要学习的东西，我们需要注意的东西，默认模式网络的活动就会受到一定程度的抑制。

And that suppression occurs not just by accident, but because the prefrontal cortex is actively suppressing it.

这种抑制的发生不仅仅是偶然的，而是因为前额叶皮层正在积极地抑制它。

In kids and adults with ADHD, the default mode network is often still active at a very robust level, even while we're trying to attend to things.

在患有多动症的儿童和成人中，即使我们正在努力关注事物，默认模式网络通常仍然处于非常活跃的水平。

And that's why someone with ADHD will sit down and try and do some focused work, and they'll start thinking about something they want or something they dislike.

这就是为什么患有多动症的人会坐下来尝试做一些专注的工作，他们会开始思考他们想要的东西或他们不喜欢的东西。

Their internal state will start to distract them.

他们的内部状态将开始分散他们的注意力。

And of course, there are other networks in the brain.

当然，大脑中还有其他网络。

There's actually what's called a true salience network.

实际上存在所谓的真正的显着性网络。

There's the dorsal attention network.

这是背部注意力网络。

There are a bunch of different networks and brain areas.

有许多不同的网络和大脑区域。

But again, when thinking about ADHD, and especially when thinking about how the drugs that we're going to talk about today work to alleviate the symptoms of ADHD, and in thinking about why so many people use or even abuse these drugs for sake of learning or recreationally, we might say, you start to realize that everything centers back to the prefrontal cortex and the prefrontal cortex's ability to actively suppress and actively enhance the activity of these multiple brain networks, including default mode network, salience network, dorsal attention network, et cetera.

但同样，当思考多动症时，特别是当思考我们今天要讨论的药物如何缓解多动症的症状时，以及思考为什么这么多人为了学习或娱乐而使用甚至滥用这些药物时，我们可能会说，你开始意识到一切都集中在前额叶皮层和前额叶皮层主动抑制和主动增强这些多个大脑网络的活动的能力，包括默认模式网络、显着网络、背侧注意网络、等等。

So rather than overwhelm you with a bunch of names of brain areas and brain networks, today I'd really like our discussion to focus on, first, what the various drugs that are used to treat ADHD are.

因此，今天我真的希望我们的讨论重点关注，首先，用于治疗多动症的各种药物是什么，而不是用一堆大脑区域和大脑网络的名称让您不知所措。

That is, how do they work at the level of neurons?

也就是说，它们如何在神经元水平上发挥作用？

Second, how they create a certain set of conditions that allow the prefrontal cortex to be a better conductor.

其次，它们如何创造一组特定的条件，使前额叶皮层成为更好的导体。

Third, how that can be leveraged during development to actually teach the prefrontal cortex of a young child to learn to be a better conductor.

第三，如何在发育过程中利用这一点来真正教导幼儿的前额叶皮层学习成为更好的指挥家。

Because that's really the hallmark of the use of these drugs, is to try and enhance the activity of particular circuits to create a sort of learning so that the prefrontal cortex is much more efficient at doing its job of conducting.

因为这确实是使用这些药物的标志，就是尝试增强特定回路的活动，以创造一种学习能力，从而使前额叶皮层更有效地完成其传导工作。

And then fourth, we're going to talk about the various things that I think most people out there ask about when they hear about drugs like Adderall, Vyvanse, and Ritalin, et cetera, which is, are they addictive?

第四，我们将讨论我认为大多数人在听到阿得拉（Adderall）、维凡斯（Vyvanse）和利他林（Ritalin）等药物时都会问到的各种问题，即它们是否会上瘾？

Why are they addictive?

为什么它们会上瘾？

Can one use them briefly or even from time to time and still be okay?

人们可以短暂使用它们，甚至偶尔使用它们，但仍然没问题吗？

What if I use them as a child and I don't want to be on them anymore?

如果我小时候使用它们并且不想再使用它们怎么办？

Should I put my child on these drugs, et cetera?

我应该让我的孩子服用这些药物等吗？

It is, I believe, only by understanding the biology of how these drugs work and their potential both to improve brain function, but also some of the dangers associated with these drugs, that one can really answer those questions for themselves or for their children.

我相信，只有了解这些药物如何发挥作用的生物学原理、它们改善大脑功能的潜力以及与这些药物相关的一些危险，人们才能真正为自己或孩子解答这些问题。

Okay, so let's start with a very basic but critical question, which is, why in the world would amphetamines, speed, or other stimulants improve the symptoms of ADHD?

好吧，让我们从一个非常基本但关键的问题开始，那就是，为什么安非他明、速度或其他兴奋剂会改善多动症的症状？

That's so critical to answer because if you think about it, the prefrontal cortex needs to coordinate the actions of these other circuits.

回答这个问题非常重要，因为如果你仔细想想，前额叶皮层需要协调这些其他电路的动作。

And so just increasing the amount of activity in prefrontal cortex, you can imagine would create a state of hyperfocus perhaps, but actually that's not the case.

因此，只要增加前额叶皮层的活动量，您就可以想象可能会产生一种高度专注的状态，但实际上情况并非如此。

If you just were to ramp up the activity of prefrontal cortex, what you would find is that somebody would become even less efficient at paying attention to what they wanted to.

如果你只是想增强前额叶皮层的活动，你会发现有人在关注他们想要关注的事情时效率会更低。

Rather, they would pay attention to whatever was presented in front of them with laser focus.

相反，他们会用激光聚焦来关注呈现在他们面前的任何东西。

They would lock on to essentially anything, and that's not good.

他们基本上会锁定任何东西，这不好。

One of the key things about prefrontal cortex is that it needs to be flexible.

前额叶皮层的关键之一是它需要灵活性。

It needs to be able to pay attention to this, then it needs to be able to pay attention to that, then it needs to go back to paying attention to the thing it was paying attention to previously, and so on and so forth.

它需要能够关注这个，然后它需要能够关注那个，然后它需要回去关注它之前关注的事情，等等。

Life, that is an effective, adaptive life, a good life, consists of self-directing one's attention most all of the time.

生活，即一种有效的、适应性的生活，一种美好的生活，是由时时刻刻自我引导的生活组成的。

So why would stimulants do that?

那么为什么兴奋剂会有这样的作用呢？

Well, almost all, not all, but almost all of the drugs used to treat ADHD fall under the category of stimulants or what are called sympathomimetics.

好吧，几乎所有，不是全部，但几乎所有用于治疗多动症的药物都属于兴奋剂或拟交感神经药的范畴。

Sympathomimetic refers to the fact that we naturally have a component of our nervous system called the autonomic nervous system.

拟交感神经是指我们的神经系统天然有一个组成部分，称为自主神经系统。

The autonomic nervous system has two major components.

自主神经系统有两个主要组成部分。

One is called the sympathetic arm of the autonomic nervous system.

其中之一称为自主神经系统的交感臂。

Has nothing to do with sympathy.

与同情心无关。

It has everything to do with ramping up our level of attention and arousal.

它与提高我们的注意力和唤醒水平密切相关。

It is the so-called fight or flight aspect of our nervous system, or rather it mediates fight or flight, but it mediates a bunch of other things too, including sexual arousal, including excitement and focus about something that we want to learn or somebody that we want to learn more about, or remembering a phone number, or anything that puts us into a state of alertness and focus.

这是我们神经系统所谓的“战斗或逃跑”方面，或者更确切地说，它介导战斗或逃跑，但它也介导许多其他事情，包括性唤起，包括对我们想要了解的东西或我们想要更多了解的人的兴奋和专注，或者记住一个电话号码，或者任何让我们进入警觉和专注状态的事情。

The other arm of the autonomic nervous system is the so-called parasympathetic arm of the autonomic nervous system, and that's often referred to as the so-called rest and digest component of our nervous system.

自主神经系统的另一臂是所谓的自主神经系统的副交感臂，通常被称为我们神经系统的所谓的休息和消化部分。

And yes, it controls rest.

是的，它控制着休息。

Indeed, it puts us into sleep.

事实上，它让我们进入睡眠状态。

And yes, it's involved in digestion, but it's involved in a bunch of other things as well, including sexual arousal, including rates of digestion, including salivation, including all sorts of things that don't just have to do with resting and digesting.

是的，它与消化有关，但它也与许多其他事情有关，包括性唤起，包括消化率，包括流涎，包括各种不仅仅与休息和消化有关的事情。

The way to think about the autonomic nervous system is it's a sort of seesaw.

思考自主神经系统的方式是它是一种跷跷板。

So it's always at a balance someplace between either predominantly sympathetic or predominantly parasympathetic, but both the parasympathetic and the sympathetic arms of the autonomic nervous system are always active all the time.

因此，它总是在交感神经占主导地位或副交感神经占主导地位之间保持平衡，但自主神经系统的副交感神经和交感神经始终处于活跃状态。

It's not as if one is completely active and the other is shut off.

这并不像是一个完全活跃而另一个完全关闭的情况。

Even in sleep, your sympathetic nervous system is not completely turned off, and even during a panic attack, your parasympathetic nervous system is not completely turned off.

即使在睡眠中，您的交感神经系统也没有完全关闭，即使在惊恐发作期间，您的副交感神经系统也没有完全关闭。

Drugs to treat ADHD, which fall under the category of stimulants, are sympathomimetics because they trigger the release of neurochemicals and the activation of components of our nervous system that very much resemble the activation of the so-called sympathetic nervous system, the one that makes us more alert and more aroused.

治疗多动症的药物属于兴奋剂类别，属于拟交感神经药，因为它们会触发神经化学物质的释放和神经系统成分的激活，这与所谓的交感神经系统的激活非常相似，交感神经系统使我们更加警觉和兴奋。

So that's why they're called sympathomimetics.

这就是为什么它们被称为拟交感神经药。

And the word stimulant refers to a general category of drugs that are sympathomimetics.

兴奋剂一词指的是拟交感神经药的一般类别。

Now, the most commonly discussed sympathomimetic is one that fortunately is not prescribed for ADHD, and that's methamphetamine.

现在，最常讨论的拟交感神经药是甲基苯丙胺，幸运的是，它不是治疗多动症的处方药。

These days, we hear a lot about meth.

这些天，我们听到很多关于冰毒的消息。

Meth, which is methylated amphetamine, is an extremely potent sympathomimetic, and it has tremendous abuse potential.

冰毒是甲基化安非他明，是一种极其有效的拟交感神经药，并且具有巨大的滥用潜力。

Believe it or not, meth, or methamphetamine, is actually available as a prescription drug, but it is used very rarely because of its high abuse potential and all the terrible things that it can do in terms of cardiovascular health, in terms of oral health, right?

信不信由你，冰毒或甲基苯丙胺实际上可以作为处方药使用，但它很少被使用，因为它具有很高的滥用潜力，而且它对心血管健康和口腔健康都有不良影响，对吗？

There's this stereotype that meth users have very degraded teeth, and indeed they do.

人们普遍认为吸毒者的牙齿退化严重，事实也确实如此。

There's a reason for that related to how meth impacts the brain and body.

其原因与冰毒如何影响大脑和身体有关。

I'm going to talk a little bit about methamphetamine a little bit later, but let's just place methamphetamine high on the shelf as the most potent sympathomimetic that's out there.

稍后我将讨论一下甲基苯丙胺，但我们先将甲基苯丙胺作为最有效的拟交感神经药放在货架上。

Because even though it's not often prescribed for ADHD, there are a class of compounds very similar to it that have a very similar pattern of action that is not quite as potent, but that leverages the same underlying mechanisms, and they are very commonly prescribed for ADHD, namely Adderall and Vyvanse.

因为尽管它不常被用于治疗多动症，但有一类与其非常相似的化合物，具有非常相似的作用模式，虽然不太有效，但利用了相同的潜在机制，并且它们非常常被用于治疗多动症，即 Adderall 和 Vyvanse。

So first, let's talk about Adderall and what Adderall is.

首先，我们来谈谈阿得拉以及什么是阿得拉。

Adderall is a combination of what are called amphetamine salts.

Adderall 是所谓的安非他明盐的组合。

Amphetamine salts refers to the fact that there are two major forms of amphetamine.

安非他明盐是指安非他明有两种主要形式。

There's a D-amphetamine, or dextroamphetamine, and levoamphetamine, or L-amphetamine.

有 D-安非他明（或右旋安非他明）和左旋安非他明（或 L-安非他明）。

So I'll refer to these as D- and L-amphetamine.

所以我将它们称为 D- 和 L-安非他明。

And for you chemistry-minded folks out there, the D and the L also refer to the fact that there is a L, left-handed version of the molecule, and there's a D, or right-handed version of the molecule.

对于那些有化学头脑的人来说，D 和 L 还指的是这样一个事实：有一个 L，即分子的左手版本，还有一个 D，即分子的右手版本。

This is only important to understand insofar as you know that the D and the L forms of the molecule look very similar, but they're mirror images of one another, and yet they can have very different actions in the brain and body.

理解这一点很重要，因为您知道分子的 D 和 L 形式看起来非常相似，但它们是彼此的镜像，但它们在大脑和身体中可以有非常不同的作用。

So Adderall is a three-to-one ratio of D-amphetamine to L-amphetamine.

因此，Adderall 是 D-安非他明与 L-安非他明的三比一比例。

You should know that L-amphetamine tends to be less potent in increasing certain neurochemicals in the brain, I'll talk about which neurochemicals they are in a moment, than is D-amphetamine.

您应该知道，L-苯丙胺在增加大脑中某些神经化学物质方面的效力往往不如 D-苯丙胺，我稍后会讨论它们是哪些神经化学物质。

So D-amphetamine is potent stuff.

所以D-安非他明是一种有效的东西。

Not as potent as methamphetamine, but very potent stuff.

不如甲基苯丙胺那么有效，但非常有效的东西。

L-amphetamine, a little bit less potent.

L-安非他明，效力稍弱。

L-amphetamine tends to be the amphetamine that increases blood pressure and heart rate, what we call peripheral effects, because it happens in the periphery, outside the central nervous system.

L-苯丙胺往往会增加血压和心率，我们称之为外周效应，因为它发生在中枢神经系统之外的外周。

Peripheral effects like increased heart rate, increased blood pressure, sweating, et cetera, are mostly activated by L-amphetamine.

心率加快、血压升高、出汗等外周效应主要是由左旋苯丙胺激活的。

Whereas D-amphetamine tends to work mainly on receptors in the brain and therefore have effects mainly restricted to the brain.

而 D-苯丙胺主要作用于大脑中的受体，因此其作用主要限于大脑。

Now, what are these effects that I've been referring to?

现在，我刚才提到的这些影响是什么？

The major effect of Adderall and other sympathomimetic stimulants is to increase the activity of two neurochemicals.

阿得拉和其他拟交感神经兴奋剂的主要作用是增加两种神经化学物质的活性。

The first of those neurochemicals is dopamine, and the other of those neurochemicals is norepinephrine.

第一种神经化学物质是多巴胺，另一种神经化学物质是去甲肾上腺素。

First off, I want to be clear that when I say norepinephrine, I could just as easily say noradrenaline, because those are the exact same thing.

首先，我想澄清的是，当我说去甲肾上腺素时，我可以很容易地说去甲肾上腺素，因为它们是完全相同的东西。

And forgive me, even though I wasn't the one to name the same thing two different things, I'll try and stay with norepinephrine, but I may say noradrenaline.

请原谅我，即使我不是那个将同一件事命名为两个不同事物的人，我会尝试继续使用去甲肾上腺素，但我可能会说去甲肾上腺素。

They are the same thing.

它们是同一件事。

There's a whole story as to how they got named two different things, but it's the same thing.

关于它们如何被命名为两个不同的东西有一个完整的故事，但它是同一件事。

The major effect of Adderall and other sympathomimetic stimulants is to increase the transmission of dopamine and norepinephrine.

阿得拉和其他拟交感神经兴奋剂的主要作用是增加多巴胺和去甲肾上腺素的传输。

So what is dopamine and what is norepinephrine?

那么什么是多巴胺，什么是去甲肾上腺素？

Well, both dopamine and norepinephrine are what are called neuromodulators.

嗯，多巴胺和去甲肾上腺素都是所谓的神经调节剂。

That is, they have the ability to increase or decrease the firing patterns, the electrical activity of particular brain circuits.

也就是说，它们能够增加或减少特定大脑回路的放电模式和电活动。

Both dopamine and norepinephrine have separate roles in creating certain states within our brain and body, but they like to collaborate, meaning they tend to be released at similar locations in the brain in order to deliver us to a particular state of mind and/or body.

多巴胺和去甲肾上腺素在我们的大脑和身体内创造某些状态方面发挥着各自的作用，但它们喜欢合作，这意味着它们往往在大脑中的相似位置释放，以便将我们带到特定的精神和/或身体状态。

So if we were to take a look at just dopamine, we would find that dopamine is released at sites within the brain and increases the activity of brain networks that, for the most part, lead to increases in motivation, pursuit, and to some extent, mood.

因此，如果我们只观察多巴胺，我们会发现多巴胺在大脑内的某个部位释放，并增加大脑网络的活动，这在很大程度上会导致动机、追求以及在某种程度上的情绪增加。

If we were to look at norepinephrine and where it's released in the brain, it tends to be released at many, not all, but many of the same sites where dopamine is released.

如果我们要观察去甲肾上腺素及其在大脑中的释放位置，就会发现它往往在许多（不是全部）但与多巴胺释放的位置相同的位置释放。

And the main function of norepinephrine is to increase the activity of neural networks that are involved in attention and focus to particular things in our environment.

去甲肾上腺素的主要功能是增加神经网络的活动，这些神经网络涉及注意力并集中于我们环境中的特定事物。

Okay, so think of dopamine and norepinephrine as collaborators, because indeed they are, and actually, they're very neurochemically similar as well.

好的，所以将多巴胺和去甲肾上腺素视为合作者，因为它们确实是，而且实际上，它们在神经化学上也非常相似。

It actually just takes one chemical conversion to turn dopamine into norepinephrine.

实际上只需要一次化学转化就能将多巴胺转化为去甲肾上腺素。

So they are very similar.

所以它们非常相似。

They're like close cousins that work together to help us achieve a common goal that involves increased motivation, focus, and alertness.

他们就像近亲一样，共同努力帮助我们实现共同的目标，包括提高动力、注意力和警觉性。

So when we talk about attention in ADHD, or we talk about quieting the hyperactivity or impulsivity of ADHD, one of the reasons why drugs that are effective in treating ADHD are so effective is because they increase motivation, focus, and alertness, and they tend to do that at very focal locations in the brain.

因此，当我们谈论多动症的注意力时，或者我们谈论平息多动症的多动或冲动时，治疗多动症的药物如此有效的原因之一是因为它们可以增加动机、注意力和警觉性，而且它们往往会在大脑中非常集中的位置发挥作用。

It's worth taking a couple of minutes to think about how sympathomimetics such as Adderall actually increase dopamine and norepinephrine.

值得花几分钟思考一下阿得拉等拟交感神经药实际上是如何增加多巴胺和去甲肾上腺素的。

They do so by affecting a couple of specific operations at the so-called synapse.

它们通过影响所谓突触的一些特定操作来实现这一点。

What are synapses?

什么是突触？

Synapses are the communication points between neurons.

突触是神经元之间的通讯点。

They're actually the spaces between neurons, but that's where a lot of the action is when neurons, as we say, are stimulating the next neuron or activating the next neuron or inhibiting the next neuron.

它们实际上是神经元之间的空间，但正如我们所说，当神经元刺激下一个神经元或激活下一个神经元或抑制下一个神经元时，这就是许多动作发生的地方。

The word neuron just simply refers to nerve cell.

神经元一词仅指神经细胞。

And so what nerve cells have is they have a cell body that contains their DNA and a bunch of other stuff.

神经细胞所拥有的就是它们有一个细胞体，其中包含它们的 DNA 和一堆其他东西。

They have a long wire-like process, which is referred to as an axon.

它们有一个长的线状突起，称为轴突。

And at the end of that axon, there are a bunch of proteins in there that do really interesting things.

在轴突的末端，有一堆蛋白质可以做非常有趣的事情。

So for instance, there are proteins down at the end of the axon that package neurotransmitter into little spherical things that we call vesicles.

例如，轴突末端的蛋白质将神经递质包装成小球形物体，我们称之为囊泡。

Those vesicles can fuse with the end of the axon and vomit the contents, those neurotransmitters, into the synaptic cleft, into that little space between neurons.

这些囊泡可以与轴突末端融合，并将内容物、那些神经递质吐到突触间隙、神经元之间的小空间中。

And then if enough of those neurotransmitters bind to receptors on what's called the postsynaptic side, which simply means the neuron on the other side, well then the next neuron will become active, and then the signal will propagate from one neuron to the next.

然后，如果足够多的神经递质与突触后侧的受体结合，即另一侧的神经元，那么下一个神经元将变得活跃，然后信号将从一个神经元传播到下一个神经元。

Now, I just described that whole process pretty quickly, and I like to think pretty simply, but it actually involves a lot of different protein bits and some pretty complex machinery in order to make that happen.

现在，我只是很快地描述了整个过程，我喜欢思考得非常简单，但它实际上涉及许多不同的蛋白质片段和一些非常复杂的机制才能实现这一点。

I don't want to overcomplicate our conversation, but what I will tell you is that down in the synapse, in the presynaptic terminal, the neuron that is going to release neurotransmitter, there are what are called transporters, which sit there and suck up or suck back up some of the neurotransmitter that's been released.

我不想让我们的谈话过于复杂，但我要告诉你的是，在突触下方，在突触前末梢，即将释放神经递质的神经元，有所谓的转运蛋白，它们坐在那里吸收或吸回一些已释放的神经递质。

There are dopamine transporters, and there are norepinephrine or noradrenergic transporters down in the synapse.

突触中有多巴胺转运蛋白，还有去甲肾上腺素或去甲肾上腺素能转运蛋白。

What Adderall does, and what other sympathomimetics do, is to inhibit or disrupt the action of those transporters.

阿德拉和其他拟交感神经药的作用是抑制或破坏这些转运蛋白的作用。

And the net consequence of that is that when dopamine and norepinephrine are released into the synapse, more of it is allowed to stick around and to bind to receptors on the postsynaptic cell than would be the case if Adderall or the other stimulant were not present in the system.

其最终结果是，当多巴胺和去甲肾上腺素释放到突触中时，与系统中不存在阿得拉或其他兴奋剂的情况相比，更多的多巴胺和去甲肾上腺素被允许粘附并与突触后细胞上的受体结合。

So one way that Adderall increases dopamine and norepinephrine is by disrupting the activity of these presynaptic transporters for dopamine and norepinephrine.

因此，阿得拉增加多巴胺和去甲肾上腺素的一种方法是破坏这些多巴胺和去甲肾上腺素的突触前转运蛋白的活性。

The other way that Adderall increases dopamine and norepinephrine is that it disrupts the activity of a different piece of machinery in the presynaptic neuron, which is called a VMAT, the vesicle monoamine transporter 2, if you really want to get specific.

Adderall 增加多巴胺和去甲肾上腺素的另一种方式是，它会破坏突触前神经元中另一部分机器的活动，如果你真的想具体了解的话，这部分机器被称为 VMAT，即囊泡单胺转运蛋白 2。

You don't have to remember these names, but what these VMATs do is actually really cool.

您不必记住这些名称，但这些 VMAT 所做的事情实际上非常酷。

What they do is they actually take whatever transmitter has been brought back up into the cell by transporters, and they package it into those vesicles that are then going to be released.

他们所做的实际上是，将转运蛋白带回细胞中的任何递质，将其包装到随后释放的囊泡中。

By disrupting the transporters that vacuum back up some of the dopamine or norepinephrine that's been released, and by also disrupting the packaging of dopamine and norepinephrine into vesicles themselves, what ends up happening is that there's a buildup of a lot more dopamine and norepinephrine in the presynaptic terminal, so that when an electrical signal travels down the neuron, now the total amount of dopamine and norepinephrine that's released is increased.

通过破坏真空回收一些已释放的多巴胺或去甲肾上腺素的转运蛋白，并破坏多巴胺和去甲肾上腺素本身包装到囊泡中，最终发生的情况是，突触前末端会积聚更多的多巴胺和去甲肾上腺素，因此，当电信号沿着神经元传播时，现在多巴胺和去甲肾上腺素的总量是释放量增加。

Okay?

好的？

So what's happening when you take Adderall is that you're getting more out of the dopamine and norepinephrine that you're releasing, and you're releasing more dopamine and norepinephrine altogether.

因此，当您服用阿得拉时，您会从释放的多巴胺和去甲肾上腺素中获得更多，并且总共释放更多的多巴胺和去甲肾上腺素。

And there's a third mechanism by which Adderall increases the amount of dopamine and norepinephrine present in synapses, and therefore can act on other neurons.

阿得拉还有第三种机制，可以增加突触中多巴胺和去甲肾上腺素的含量，从而作用于其他神经元。

And that has to do with disruption of the entire network between these different proteins.

这与这些不同蛋白质之间的整个网络的破坏有关。

I'm not going to go into that in any detail because it gets somewhat complicated in terms of the cell biology and some of the biochemistry down at the tips of these axons.

我不会详细讨论这一点，因为它在细胞生物学和这些轴突尖端的一些生物化学方面变得有些复杂。

But suffice to say that Adderall is such an effective sympathomimetic, that is, it can increase dopamine to such a great extent, especially compared to other treatments for ADHD, because of its ability to increase dopamine release and transmission, and therefore action, as well as noradrenergic release and transmission and action down there in the synapse.

但可以说，阿得拉是一种非常有效的拟交感神经药，也就是说，它可以在很大程度上增加多巴胺，特别是与其他治疗多动症的疗法相比，因为它能够增加多巴胺的释放和传输，从而增加作用，以及去甲肾上腺素能的释放和传输以及突触中的作用。

And it's worth pointing out that most of the effect of Adderall is in increasing dopamine as opposed to norepinephrine.

值得指出的是，阿得拉的大部分作用是增加多巴胺而不是去甲肾上腺素。

It does increase norepinephrine, but its major effects, or we should say the major effects that have made it such an attractive drug to so many people, both for the treatment of ADHD and for people to take recreationally or off prescription or for sake of studying or work simply because they want to focus more and longer, is because of its ability to increase dopamine to such a great extent.

它确实会增加去甲肾上腺素，但它的主要作用，或者我们应该说使它成为对这么多人如此有吸引力的药物的主要作用，无论是用于治疗多动症，还是人们为了娱乐或非处方或仅仅因为他们想要更多、更长时间地集中注意力而学习或工作，是因为它能够在很大程度上增加多巴胺。

Now, a bit earlier I mentioned that L-amphetamine, levoamphetamine, is present in Adderall, but at one-quarter the amount of D-amphetamine.

现在，早些时候我提到 L-安非他明（左旋安非他明）存在于阿得拉中，但含量仅为 D-安非他明的四分之一。

Okay, so there's a little bit of L-amphetamine and a lot of D-amphetamine in Adderall.

好的，阿得拉中含有少量 L-安非他明和大量 D-安非他明。

Many of you are probably familiar with Vyvanse.

你们中的许多人可能熟悉 Vyvanse。

Vyvanse is a commercial name for what many people think is extended-release Adderall, but actually, Vyvanse is not extended-release Adderall.

Vyvanse 是许多人认为是缓释阿德拉的商业名称，但实际上，Vyvanse 并不是缓释阿德拉。

Vyvanse is a drug in which the pharmaceutical industry has taken one component of Adderall, just the D-amphetamine component, and attached to it an amino acid called lysine.

Vyvanse 是一种药物，制药行业采用了 Adderall 的一个成分（即 D-安非他明成分），并在其上附加了一种称为赖氨酸的氨基酸。

Now, the amino acid lysine is a big amino acid, and the attaching of lysine to D-amphetamine, what we call Vyvanse, makes it what's called a prodrug.

现在，氨基酸赖氨酸是一种大氨基酸，赖氨酸与 D-安非他明（我们称之为 Vyvanse）的连接使其成为所谓的前药。

It actually can't have any effect on its own.

实际上它本身并不能产生任何效果。

But when one takes Vyvanse and it's broken down in the gut, but to a greater extent actually in the bloodstream, the lysines are cleaved off slowly over time.

但是，当服用 Vyvanse 时，它​​会在肠道中分解，但实际上在血液中分解的程度更大，随着时间的推移，赖氨酸会慢慢被裂解。

And as a consequence, Vyvanse is basically timed-release D-amphetamine.

因此，Vyvanse 基本上是定时释放的 D-安非他明。

Okay, this is important because I think a lot of people think that Adderall, which again, is D-amphetamine and L-amphetamine, and those two things operate quite a bit differently at the level of norepinephrine and epinephrine and cardiac versus brain effects.

好吧，这很重要，因为我认为很多人认为阿得拉（Adderall），也就是 D-安非他明和 L-安非他明，这两种物质在去甲肾上腺素和肾上腺素水平以及心脏与大脑作用方面的作用有很大不同。

A lot of people think Vyvanse is just slow-release Adderall, but it is not.

很多人认为 Vyvanse 只是缓释阿得拉，但事实并非如此。

What Vyvanse is, is D-amphetamine only, but in time-release form.

Vyvanse 只是 D-安非他明，但呈缓释形式。

And Vyvanse was actually developed as a way to try and get around, or rather prevent some of the abuse potential of Adderall and other drugs that contain D-amphetamine.

Vyvanse 实际上是作为一种尝试绕过或防止阿得拉和其他含有 D-安非他明的药物的滥用潜力而开发的。

D-amphetamine stands for dextroamphetamine, and in the '70s and '80s, there were a fair amount of movies, and there was a lot of trafficking, and there was a lot of criminal activity related to what was called Dexedrine.

D-安非他明代表右旋安非他明，在 70 年代和 80 年代，有相当多的电影，有大量的贩运活动，还有很多与所谓的 Dexedrine 相关的犯罪活动。

Dexedrine is pure D-amphetamine.

右旋苯丙胺是纯 D-安非他明。

So if we are going to be very direct, if I were going to just frame these things in the context of their neurochemistry, what I can tell you is that Vyvanse is time-release Dexedrine.

因此，如果我们要非常直接，如果我要在神经化学的背景下构建这些东西，我可以告诉你的是 Vyvanse 是缓释右旋糖苷。

Okay?

好的？

It's not time-release Adderall.

它不是缓释阿得拉。

Now, just because there were movies and reports of criminal activity related to Dexedrine, that doesn't necessarily mean that Dexedrine is not an effective and useful pharmaceutical.

现在，仅仅因为有与 Dexedrine 有关的犯罪活动的电影和报道，并不一定意味着 Dexedrine 不是一种有效且有用的药物。

And in fact, Vyvanse, which is time-release Dexedrine, has proved to be very effective in the treatment of ADHD for a lot of people.

事实上，Vyvanse（一种缓释右旋糖苷）已被证明对许多人的多动症治疗非常有效。

And the reason for that is this time release does indeed prevent abuse in the sense that despite people's many attempts, from what I hear, to increase the rate of entry of the dextroamphetamine into their system by either snorting it or, God forbid, even injecting it and things of that sort.

其原因是，这次释放确实防止了滥用，从某种意义上说，尽管人们多次尝试通过鼻吸或（上帝禁止）甚至注射之类的方式来增加右旋苯丙胺进入其系统的速度，但据我所知。

The attaching of that lysine to dextroamphetamine really does slow the absorption.

赖氨酸与右旋苯丙胺的结合确实会减慢吸收。

So when somebody takes Vyvanse, and hopefully people are taking it responsibly, when they take Vyvanse, what they're really getting is a slow trickle of dextroamphetamine into their system, and therefore a slow, long-lasting increase in dopamine and norepinephrine.

因此，当有人服用 Vyvanse 时，希望人们负责任地服用，当他们服用 Vyvanse 时，他们真正得到的是右旋苯丙胺缓慢滴入他们的系统，因此多巴胺和去甲肾上腺素缓慢而持久地增加。

And indeed, that's what happens.

事实上，事情就是这样发生的。

The effects of Vyvanse can extend over anywhere from 12 to 16, sometimes even 18 hours, depending on how quickly somebody metabolizes it.

Vyvanse 的效果可以持续 12 到 16 小时，有时甚至 18 小时，具体取决于某人代谢它的速度。

And I should say that there's no way to predict how quickly one will metabolize any of these drugs except by trying them.

我应该说，除了尝试之外，没有办法预测一个人代谢这些药物的速度有多快。

That's one of the sort of downsides of the state of things these days.

这是当今事态的缺点之一。

There's no blood test or enzymatic test that will tell you whether or not you're going to be a fast metabolizer or a slow metabolizer.

没有血液测试或酶测试可以告诉你你是一个快速代谢者还是一个慢速代谢者。

And that's why people just have to sort through different dosages, which we'll talk about in a little bit.

这就是为什么人们必须对不同的剂量进行分类，我们稍后会讨论这一点。

They have to sort through different types of sympathomimetics.

他们必须对不同类型的拟交感神经药进行分类。

Some people try Adderall, and they find that the quick time course of Adderall, or at least quick for them of about six to eight hours, is just too fast, and then it wears off, and they get into a slump in the afternoon.

有些人尝试阿得拉，他们发现阿得拉的快速疗程，或者至少对他们来说大约六到八小时的时间太快了，然后它就消失了，他们在下午陷入了低迷。

Other people find that one Adderall taken at 6:00 a.m.

其他人发现早上 6:00 服用一颗阿得拉 (Adderall)

will have them going all day long and into the night, and it's just too much stimulation, and they need to come way, way down in dose, or they need to think about other sympathomimetics for ADHD.

会让他们整天工作到晚上，这刺激太大了，他们需要大大降低剂量，或者他们需要考虑其他治疗多动症的拟交感神经药。

And we'll talk about what some of those other options are in a little bit as well.

我们还将讨论一些其他选项。

So the important thing to understand is that Adderall is really two drugs, dextroamphetamine.

因此，要了解的重要一点是，阿得拉实际上是两种药物：右旋苯丙胺。

Vyvanse is dextroamphetamine, which is also called Dexedrine, but with this time-released aspect created by lumping a lysine on there.

Vyvanse 是右旋苯丙胺，也称为 Dexedrine，但通过在其上聚集赖氨酸而产生延时释放的效果。

And you may notice that I haven't mentioned one of the major drugs used to treat ADHD, and that's Ritalin, or what's sometimes also called Concerta, depending on, again, the time-release forms, et cetera.

您可能会注意到，我没有提到用于治疗多动症的主要药物之一，那就是利他林，或者有时也称为 Concerta，这又取决于缓释形式等。

Ritalin was very commonly prescribed for the treatment of ADHD early in the days of using sympathomimetics in order to treat ADHD.

在使用拟交感神经药治疗 ADHD 的早期，利他林是非常常用的治疗 ADHD 的处方药。

So for instance, I went to college in the early '90s, so I started college in '93, and I graduated in '98.

举例来说，我在90年代初上大学，所以我在93年开始上大学，然后在98年毕业。

There was one year in there as a, let's call it a transition year.

其中有一年是过渡年。

I can recall hearing that Ritalin was being prescribed for ADHD in kids, and I, like many other people, were wondering, what are the long-term consequences of this going to be?

我记得听说利他林被用于治疗儿童多动症，我和许多其他人一样想知道，这会产生什么长期后果？

I also, like many other people, was very perplexed as to why a stimulant sympathomimetic like Ritalin was being prescribed for hyperactive kids.

和许多其他人一样，我也很困惑为什么要为多动症的孩子开出利他林这样的拟交感神经兴奋剂。

That will become clear in a moment, but we don't hear so much about Ritalin nowadays, and I think that's because Adderall and Vyvanse and things like them have become so popular for the treatment of ADHD.

这一点很快就会变得清楚，但现在我们很少听说利他林，我认为这是因为 Adderall 和 Vyvanse 以及类似的药物在治疗多动症方面变得如此流行。

It's worth noting that Ritalin is not actually amphetamine.

值得注意的是，利他林实际上并不是安非他明。

Ritalin is what's called methylphenidate, and methylphenidate works in a lot of ways that are similar to the way that Adderall and Vyvanse work, but there are certain ways in which it's different.

利他林就是所谓的哌醋甲酯，哌醋甲酯的作用方式在很多方面与 Adderall 和 Vyvanse 的作用方式相似，但也有某些方面不同。

Now, Ritalin, methylphenidate, does increase dopamine transmission at synapses, and it does so also by inhibiting the function of that presynaptic dopamine transporter that would otherwise suck more dopamine back up into the presynaptic cell.

现在，利他林（哌醋甲酯）确实增加了突触的多巴胺传递，而且它还通过抑制突触前多巴胺转运蛋白的功能来实现这一点，否则突触前多巴胺转运蛋白会将更多的多巴胺吸回突触前细胞。

Methylphenidate, Ritalin, also disrupts the activity of the noradrenergic transporter, leading to net increases in the amount of norepinephrine at the synapse.

哌醋甲酯、利他林也会破坏去甲肾上腺素转运蛋白的活性，导致突触去甲肾上腺素的量净增加。

But it is not as much a potent inhibitor of the noradrenergic transporter, and therefore, most of the effect of methylphenidate is to increase dopamine at synapses.

但它并不是去甲肾上腺素能转运蛋白的有效抑制剂，因此，哌醋甲酯的大部分作用是增加突触处的多巴胺。

A lot of people don't realize this.

很多人没有意识到这一点。

A lot of people think that Ritalin is just very short-acting Adderall, and that's not the case.

很多人认为利他林只是作用非常短的阿得拉，但事实并非如此。

It is true that Ritalin, at least in its standard form, tends to have a pretty short half-life, and therefore, its effects basically kick in about 20 to 40 minutes after taking it, sometimes a little bit sooner, sometimes a little later, and they last about four to six hours, as opposed to the six to eight hours typical of Adderall.

确实，利他林，至少在其标准形式下，往往具有相当短的半衰期，因此，其作用基本上在服用后约 20 至 40 分钟内生效，有时稍早，有时稍晚，持续约 4 至 6 小时，而不是典型的阿得拉 (Adderall) 的 6 至 8 小时。

But Ritalin is not short-acting Adderall.

但利他林并不是短效的阿得拉。

Ritalin is mainly increasing dopamine and, to some extent, norepinephrine at synapses, whereas Adderall and Vyvanse are increasing both dopamine and norepinephrine to a much greater extent.

利他林主要增加突触处的多巴胺，并在一定程度上增加去甲肾上腺素，而Adderall和Vyvanse则在更大程度上增加多巴胺和去甲肾上腺素。

And for those of you that are interested in the underlying cell biological reason for that, it has something to do with Ritalin's relatively lower affinity for the noradrenergic transporter, but it's also because, remember I listed off three mechanisms by which Adderall, and by extension Vyvanse, increase dopamine and norepinephrine transmission?

对于那些对潜在的细胞生物学原因感兴趣的人来说，这与利他林对去甲肾上腺素转运蛋白的亲和力相对较低有关，但这也是因为，还记得我列出了 Adderall 和 Vyvanse 增加多巴胺和去甲肾上腺素传输的三种机制吗？

Right, disruption of the transporter, disruption of the VMAT2, as well as a disruption of the whole kind of complex of communication between those proteins.

是的，转运蛋白的破坏，VMAT2 的破坏，以及这些蛋白质之间的整个通讯复合体的破坏。

Well, Ritalin is really only tapping into the drug's ability to disrupt the dopamine and noradrenergic transporter.

好吧，利他林实际上只是利用了药物破坏多巴胺和去甲肾上腺素转运蛋白的能力。

So it's three mechanisms of increasing dopamine and norepinephrine for Adderall and Vyvanse, and by extension, Dexedrine, and it's only one mechanism for Ritalin to increase dopamine and norepinephrine, and therein, mostly dopamine.

因此，Adderall 和 Vyvanse 以及 Dexedrine 是增加多巴胺和去甲肾上腺素的三种机制，而利他林只是增加多巴胺和去甲肾上腺素的一种机制，其中主要是多巴胺。

So if we take a step back for a moment from all these drugs and all this cell biology of neurons and so forth, and we go back to the brain networks involved in attention, remember the orchestra model or the teacher model, where the prefrontal cortex really sits in top seat in terms of coordinating the actions, both the shh, the quieting, and the yes, please speak actions of the brain, really bringing about what we think of as focused attention and task switching, all the stuff that goes along with learning and focus and cognition.

因此，如果我们从所有这些药物和神经元的细胞生物学等等中退一步，回到与注意力有关的大脑网络，记住管弦乐队模型或教师模型，其中前额叶皮层在协调动作方面确实处于最高位置，包括“嘘”、“安静”和“是的，请说话”大脑的动作，真正带来了我们所认为的集中注意力和任务切换，所有与学习和专注相关的东西以及认知。

Well, what we know is that dopamine and norepinephrine, which are differentially increased by these different drugs that we've been talking about, also differentially impact the various aspects of executive function of the prefrontal cortex, increasing our attention for specific things.

嗯，我们知道的是，我们一直在谈论的这些不同药物会不同程度地增加多巴胺和去甲肾上腺素，它们也会对前额皮质执行功能的各个方面产生不同的影响，从而增加我们对特定事物的注意力。

And while there is a lot of nuance in the literature about this, we can safely say a couple of things.

虽然文献中对此有很多细微差别，但我们可以有把握地说几件事。

First of all, increasing dopamine at particular synapses and networks in the brain can serve as what's called noise reduction.

首先，增加大脑中特定突触和网络的多巴胺可以起到所谓的降噪作用。

It can help further enhance the quieting of all that background stuff.

它可以帮助进一步增强所有背景的安静程度。

That background stuff can be attention to things in your environment, like noises or visual cues.

背景内容可以是对环境中事物的关注，例如噪音或视觉提示。

It could be some internal narrative that you had about yesterday or something that somebody said about you, or something that somebody you like would like to say about you, or whatever it may be that's happening in your head that's distracting you, as well as your representation of your internal bodily state, what we call interoception.

它可能是你昨天的一些内心叙述，或者某人对你说的一些话，或者你喜欢的人想说的关于你的事，或者任何发生在你头脑中分散你注意力的事情，以及你对你内部身体状态的表征，我们称之为内感受。

This is a really important aspect of attention that we don't often hear about, which is that we have the ability to attend to things outside of us, which is called exteroception, as well as an ability to attend to things inside of us, which include things like thoughts, but also includes, for instance, how empty or full our gut feels, whether or not we're comfortable in our chair.

这是注意力的一个非常重要的方面，但我们不经常听到，这就是我们有能力关注我们外部的事物，这被称为外感受，以及关注我们内部事物的能力，其中包括思想之类的东西，但也包括例如我们的肠道感觉有多空或多满，无论我们坐在椅子上是否舒服。

And when we think about the practice of focus and learning or focusing as a verb, it involves often forcing ourselves to sit still.

当我们将专注和学习或专注作为动词来思考时，它经常涉及强迫自己静坐。

It often involves us suppressing the fact that our foot is a little bit cramped or that we might need to use the restroom.

它常常让我们压抑自己的脚有点局促或者我们可能需要上厕所的事实。

We might want to delay that for 10, 15 minutes, even though it might be fairly urgent.

我们可能想推迟 10、15 分钟，尽管这可能相当紧急。

All these sorts of things are central to our ability to attend and focus.

所有这些事情对于我们参与和集中注意力的能力至关重要。

And so dopamine, while it does many different things in the brain, many, many different things, one of its main functions in the context of all this prefrontal cortex and attention stuff is to quiet the amount of noise.

因此，多巴胺虽然在大脑中起着许多不同的作用，很多很多不同的作用，但它在所有前额皮质和注意力方面的主要功能之一是消除噪音。

That is, it helps the prefrontal cortex suppress the signals that would otherwise distract us into thinking about, "Oh, yeah, I'm kind of thirsty right now," or, "I need to use the restroom," or, "I really want to make this call," or, "I really want to pick up my phone." All of that stuff, all of that suppression, that shh, that quieting down of all the background chatter related to things external and internal to us, in our head and our body, is greatly facilitated by having more dopamine present in the synapses that allow for what we call noise reduction.

也就是说，它帮助前额叶皮层抑制信号，否则这些信号会分散我们的注意力，让我们思考“哦，是的，我现在有点口渴”，或者“我需要使用洗手间”，或者“我真的很想打这个电话”，或者“我真的很想拿起我的电话”。所有这些东西，所有抑制，嘘，所有与我们外部和内部的事物有关的背景喋喋不休的安静，在我们的头脑和我们的身体中，通过在突触中存在更多的多巴胺来极大地促进我们所说的降噪。

Now, in parallel to that is norepinephrine.

现在，与此并行的是去甲肾上腺素。

Norepinephrine is released from multiple sites in the brain and body, but within the brain, there's one major site of neurons that manufacture norepinephrine, and the name of that site is locus coeruleus.

去甲肾上腺素从大脑和身体的多个部位释放，但在大脑内，有一个主要的神经元部位产生去甲肾上腺素，该部位的名称是蓝斑。

It sits in the back of the brain.

它位于大脑后部。

It's actually a relatively small collection of neurons, but they are very, very powerful.

它实际上是一个相对较小的神经元集合，但它们非常非常强大。

They extend their little axons, their wires, to multiple locations in the brain, and they release norepinephrine at those locations.

它们将小轴突、电线延伸到大脑的多个位置，并在这些位置释放去甲肾上腺素。

So think of them sort of as a sprinkler system that originates from one very focal location, but that can sprinkle norepinephrine at multiple locations in the brain.

因此，可以把它们想象成一种喷水系统，它起源于一个非常集中的位置，但可以在大脑的多个位置喷洒去甲肾上腺素。

And the amazing thing about locus coeruleus and that sprinkler system is that indeed, the sprinkler system can be pretty widespread, where everywhere there's a sprinkler head, somebody's getting norepinephrine, but it also can fairly focally release norepinephrine at particular sites.

蓝斑和喷水灭火系统的神奇之处在于，喷水灭火系统确实可以相当广泛，到处都有喷水喷头，有人会得到去甲肾上腺素，但它也可以在特定部位相当集中地释放去甲肾上腺素。

So while in the context of today's discussion, dopamine is acting largely to impart noise reduction, norepinephrine has the ability to boost signals at synapses to increase the amplitude and frequency of communication between neurons.

因此，在今天讨论的背景下，多巴胺主要起到降低噪音的作用，而去甲肾上腺素则能够增强突触信号，从而增加神经元之间通信的幅度和频率。

And in that way, in the context of today's discussion, norepinephrine, when released at the particular synapses in the particular brain networks that are related to attention and learning, is largely serving to increase signal.

这样，在今天讨论的背景下，去甲肾上腺素在与注意力和学习相关的特定大脑网络中的特定突触处释放时，在很大程度上有助于增加信号。

So what we have in the context of a drug like Adderall or Vyvanse, or to some extent methylphenidate, Ritalin does this as well, is an increase in dopamine and norepinephrine that is leading to two things, both a reduction in noise, a quieting of the circuitry that we don't want to hear so much from, and an increase in the signal of the networks that we do want to pay attention to.

因此，我们在阿得拉（Adderall）或维凡斯（Vyvanse），或者某种程度上哌醋甲酯（Ritalin）等药物的背景下，多巴胺和去甲肾上腺素的增加会导致两件事，一是减少噪音，使我们不想听到太多的电路安静下来，二是增加我们确实想要关注的网络信号。

And the net effect of that noise reduction and signal amplification is what the engineers refer to as increased signal-to-noise.

降噪和信号放大的净效应就是工程师所说的信噪比增加。

And the consequence of that is a heightened subjective sense or ability to decide what we want to focus on, sit down or stand there, and just focus on it.

其结果是增强了主观意识或能力来决定我们想要关注什么，坐下或站在那里，然后专注于它。

So the way that we've been discussing drugs to treat ADHD and their ability to increase dopamine and norepinephrine, and thereby to reduce the amount of noise, so to speak, in the brain, and to increase the amount of signal related to things that we want to attend to, all presumes that the amount of dopamine and the amount of norepinephrine that's being increased is perfect for what we want to accomplish, which is increased focus and reduced hyperactivity and impulsivity.

因此，我们一直在讨论治疗多动症的药物及其增加多巴胺和去甲肾上腺素的能力，从而减少大脑中的噪音量，并增加与我们想要关注的事情相关的信号量，所有这些都假设增加的多巴胺和去甲肾上腺素的量非常适合我们想要实现的目标，即增加注意力并减少多动和冲动。

But of course, in the real world, that's not always the case.

但当然，在现实世界中，情况并非总是如此。

Depending on the dosage of the drug, one's sensitivity to the drug, even what stage of development across the lifespan a person is at, things can really go haywire pretty fast.

根据药物的剂量、一个人对药物的敏感性，甚至一个人在一生中处于哪个发育阶段，事情可能会很快变得混乱。

And what I'm referring to when I say haywire is, if you think about dopamine and its ability to reduce noise, well, dopamine does a bunch of other things as well.

当我说混乱时，我指的是，如果你想到多巴胺及其减少噪音的能力，那么，多巴胺还有很多其他作用。

And in fact, we know that if dopamine is increased too much in the brain of somebody that has ADHD or somebody that doesn't have ADHD, people can become euphoric, people can become manic, people can even become psychotic.

事实上，我们知道，如果患有多动症的人或没有多动症的人大脑中的多巴胺过多，人们就会变得欣快，人们可能变得躁狂，人们甚至可能变得精神病。

Likewise, if norepinephrine is increased too much, people won't just become alert, they will become very anxious, have panic attacks, and depending on the drug they're taking, they may even experience very serious peripheral symptoms, meaning elevated heart rate and sweating that is super uncomfortable, and on and on.

同样，如果去甲肾上腺素增加太多，人们不仅会变得警觉，他们还会变得非常焦虑，惊恐发作，根据他们服用的药物，他们甚至可能会经历非常严重的外周症状，这意味着心率加快和出汗，非常不舒服，等等。

So everything I've been discussing up until now is true, but I want to make it clear that it's true in the context of appropriately dosed prescribed drug for a given condition.

因此，到目前为止我所讨论的一切都是正确的，但我想澄清的是，在针对特定情况服用适当剂量的处方药的情况下，这是正确的。

Which leads us to the next question, which is why would it be that giving these drugs, which are in fact stimulants, why would that calm a kid down?

这就引出了下一个问题，即为什么给予这些实际上是兴奋剂的药物，为什么会让孩子平静下来？

Why would that calm an adult with ADHD down?

为什么这会让患有多动症的成年人平静下来？

And the answer to that is not completely straightforward, and it is worth pointing out that not everyone with ADHD has impulsivity and hyperactivity, and therefore an inability to focus.

这个问题的答案并不完全简单，值得指出的是，并不是每个患有多动症的人都会冲动和多动，因此无法集中注意力。

Some kids and adults with ADHD do have challenges with impulsivity and hyperactivity.

一些患有多动症的儿童和成人确实面临着冲动和多动的挑战。

Some do not.

有些则不然。

Some just have challenges with focus.

有些人只是在专注方面遇到挑战。

And I did an entire episode about ADHD, and we are going to have an expert guest on this podcast who specializes in the treatment of ADHD to talk about some of these issues further.

我做了一整集关于多动症的节目，我们将在这个播客中邀请一位专门研究多动症治疗的专家来进一步讨论其中的一些问题。

But I just want to remind everybody that, as in the general population, children and adults with ADHD are capable of very concentrated periods of focus.

但我只是想提醒大家，与一般人群一样，患有注意力缺陷多动症的儿童和成人能够在一段时间内注意力高度集中。

The pattern, however, tends to be that children and adults with ADHD have a harder time getting into that state of focus.

然而，这种模式往往是患有多动症的儿童和成人更难进入那种专注状态。

And perhaps most importantly, they have a very hard time getting into a forced state of focus for things that they don't enjoy doing.

也许最重要的是，他们很难被迫专注于自己不喜欢做的事情。

I'm sure many of you are also thinking, "Wait, I don't like to do certain things, and it's harder to focus on those things than on the things I like.

我相信你们很多人也在想，“等等，我不喜欢做某些事情，而且专注于这些事情比专注于我喜欢的事情更难。

Of course.

当然。

Does that mean I have ADHD?" And the answer is not necessarily so.

这是否意味着我患有多动症？”而答案也不一定如此。

Kids and adults with ADHD exhibit an extreme variation in their ability to focus, such that if there's something they really, really like doing, they can indeed focus.

患有注意力缺陷多动症的儿童和成人在集中注意力的能力上表现出极大的差异，因此，如果他们真的非常喜欢做某件事，他们确实可以集中注意力。

However, for many, many other activities that are required in order to develop, I guess we'll just call it normal life advancement, so sitting still, listening to conversations that we may or may not be particularly interested in, that's where the challenges come about.

然而，对于发展所需的许多其他活动，我想我们只会称之为正常的生活进步，所以静静地坐着，听我们可能特别感兴趣或可能不特别感兴趣的对话，这就是挑战的来源。

So the point is that these brain networks and these neuromodulators like dopamine and norepinephrine that we've been talking about in fairly straightforward terms as it relates to a drug's ability to increase their transmission, and therefore an improved ability of focus, presumes two things.

所以重点是，这些大脑网络和这些神经调节剂（如多巴胺和去甲肾上腺素）我们一直在以相当简单的术语谈论，因为它与药物增加其传输的能力有关，因此提高了注意力的能力，假定了两件事。

It presumes that the dosing is right.

假定剂量是正确的。

That is, that the levels of increases in these neuromodulators is just right.

也就是说，这些神经调节剂的增加水平恰到好处。

And I also just want to acknowledge that ADHD is, first of all, not an inability to focus at all.

我也想承认，首先，注意力缺陷多动症根本不是无法集中注意力。

It is immense challenges in focusing on lots of different things as required for normal life progression.

关注正常生活发展所需的许多不同事物是巨大的挑战。

And it's also the case that there is no one specific pattern of ADHD that applies to everyone with ADHD.

而且，没有一种特定的 ADHD 模式适用于所有 ADHD 患者。

Some people, both kids and adults, will exhibit the hyperactivity, but not the impulsivity, although those two things tend to go hand in hand.

有些人，无论是儿童还是成人，都会表现出多动症，但不会表现出冲动，尽管这两件事往往是齐头并进的。

Some people will have a challenge in focus without hyperactivity, impulsivity, and so forth.

有些人会在注意力不集中的情况下遇到多动、冲动等问题。

And all this just really speaks to the complexity of ADHD.

所有这些都真正说明了多动症的复杂性。

And yet, we can confidently say that there are more drugs to treat ADHD than any other psychiatric condition.

然而，我们可以自信地说，治疗多动症的药物比任何其他精神疾病都多。

We've talked about a few of those now, but among those, Adderall, Vyvanse, Ritalin, also called methylphenidate, there are time-release versions.

我们现在已经讨论了其中的一些，但其中有阿得拉（Adderall）、维凡斯（Vyvanse）、利他林（也称为哌醋甲酯），有缓释版本。

There are different variations on those time-release versions.

这些临时发布版本有不同的变体。

There's even straight Dexedrine, which is prescribed for ADHD in some cases, and on and on.

甚至还有直接使用的 Dexedrine，在某些情况下用于治疗多动症，等等。

And you might also find it interesting to know that that very large kit of drugs, all of which, at least the ones we've talked about so far, are sympathomimetics or stimulants, are more effective at treating ADHD than are any other collection of drugs for treating other psychiatric disorders.

您可能还会发现有趣的是，这个非常大的药物套件，所有这些药物，至少是我们到目前为止讨论的那些，都是拟交感神经药或兴奋剂，在治疗多动症方面比任何其他治疗其他精神疾病的药物更有效。

So what all of that diversity of symptomology in ADHD, as well as differences in sensitivity to drugs and individual variation, what all of that speaks to is that the large kit of drugs that's out there is designed to be assessed with the careful consult of a very qualified psychiatrist in order to allow the child or adult to arrive at the specific drug and the specific dosage that's ideal for their particular pattern of ADHD.

因此，ADHD 症状的多样性，以及对药物敏感性的差异和个体差异，所有这些都表明，现有的大量药物是经过非常合格的精神科医生的仔细咨询而设计的，以便让儿童或成人找到适合其特定 ADHD 模式的特定药物和特定剂量。

And that issue actually gives rise to the answer to that now somewhat age-old question as to why giving stimulants to a kid that is hyperactive would calm them down.

这个问题实际上回答了一个现在有些古老的问题，即为什么给一个多动的孩子服用兴奋剂会让他们平静下来。

And the answer is that the hyperactivity, impulsivity, and focus issues present in ADHD in children and adults are the consequence not necessarily of deficient activity of neural circuits in the prefrontal cortex or deficient activity of the default mode network or deficient activity of the salience network, et cetera.

答案是，儿童和成人 ADHD 中存在的多动、冲动和注意力问题不一定是前额皮质神经回路活动不足、默认模式网络活动不足或显着网络活动不足等造成的。

What appears to be the case, based on a lot of high-quality neuroimaging data, is that the brains of children and adults with ADHD have all of these networks functioning, but those networks are actually hyper-connected.

根据大量高质量的神经影像数据，事实似乎是，患有多动症的儿童和成人的大脑中所有这些网络都在发挥作用，但这些网络实际上是超连接的。

That is, they tend to be co-active at times when ordinarily, meaning in kids and adults without ADHD, they would not be co-active.

也就是说，他们有时会表现出积极的态度，而通常情况下，对于没有多动症的儿童和成人来说，他们不会表现出积极的态度。

So that's an important point because it's easy to get the impression that ADHD is just a deficiency in dopamine and norepinephrine, and that's simply not the case.

所以这一点很重要，因为人们很容易认为多动症只是多巴胺和去甲肾上腺素缺乏，但事实并非如此。

If you recall, dopamine and norepinephrine are neuromodulators.

如果您还记得的话，多巴胺和去甲肾上腺素是神经调节剂。

They modulate the activity of other neural circuits, and they can both increase and decrease activity within those circuits.

它们调节其他神经回路的活动，并且可以增加或减少这些回路内的活动。

So you don't necessarily want to think about dopamine and norepinephrine just as molecules that increase neural activity.

因此，您不一定要将多巴胺和去甲肾上腺素视为增加神经活动的分子。

And you certainly don't want to think about ADHD as just a deficiency in dopamine or a deficiency in norepinephrine.

您当然不想将注意力缺陷多动症仅仅视为多巴胺或去甲肾上腺素缺乏。

The way these drugs work when they are used effectively to treat ADHD is to tune the amount of dopamine and norepinephrine that are present in particular brain networks in order to allow the person to arrive at just the right balance between the activation of these different neural circuits, causing them largely to be less synchronous in their firing.

当这些药物有效地用于治疗多动症时，其作用方式是调节特定大脑网络中存在的多巴胺和去甲肾上腺素的量，以便使人在这些不同神经回路的激活之间达到适当的平衡，从而导致它们在很大程度上不那么同步。

So this takes us back to this question of why giving stimulants to a kid would calm them down.

所以这让我们回到这个问题：为什么给孩子服用兴奋剂会让他们平静下来。

It's not so much that you're giving a stimulant to a kid to place them into a state of calm.

这并不是说你给孩子注射兴奋剂，让他们进入平静的状态。

I think that's a common misconception.

我认为这是一个常见的误解。

Rather, by increasing dopamine and norepinephrine, these drugs, yes, increase levels of overall autonomic arousal.

相反，通过增加多巴胺和去甲肾上腺素，这些药物确实可以提高整体自主神经兴奋水平。

They are, after all, sympathomimetics.

毕竟，它们是拟交感神经药。

But more importantly to the treatment of ADHD symptoms, you are activating the prefrontal cortex in a way that allows it to be more of a coordinator of that orchestra conductor, or if you prefer the analogy to a teacher in the classroom, to ramp up the activity of certain neural circuits in a given moment and shh, quiet down the activity of other neural circuits such that the default mode network can still perform its incredible actions.

但对于治疗多动症症状更重要的是，你正在激活前额皮质，使其更像是管弦乐队指挥的协调员，或者如果你更喜欢课堂上老师的类比，在给定时刻增强某些神经回路的活动，嘘，安静其他神经回路的活动，这样默认模式网络仍然可以执行其令人难以置信的动作。

After all, the default mode network is involved not just in self-referencing and kind of daydreaming, but also creativity and imagination.

毕竟，默认模式网络不仅涉及自我参照和白日梦，还涉及创造力和想象力。

That's been well described in the literature, as well as the salience network and these other networks that are designed to drop us into very narrow trenches of attention These drugs for the treatment of ADHD are indeed stimulants, but the goal of prescribing these drugs to a child or adult with ADHD is to adjust dosage, timing, and the duration over which somebody takes it in their lifespan in order to allow those neural circuits to work in the proper way.

文献中已经对此进行了很好的描述，显着网络和其他网络旨在让我们陷入非常狭窄的注意力范围。这些治疗多动症的药物确实是兴奋剂，但给患有多动症的儿童或成人开这些药物的目的是调整剂量、时间和某人在其一生中服用药物的持续时间，以便让这些神经回路以正确的方式工作。

Meaning for the conductor to activate the instruments in that little symphony or band in the appropriate order in order to arrive at the right music, as opposed to all the instruments playing at once, which would just be complete noise.

这意味着指挥家以适当的顺序激活小型交响乐或乐队中的乐器，以便达到正确的音乐，而不是同时演奏所有乐器，这只是完全的噪音。

Or again, if you prefer the classroom teaching analogy, for the teacher to call on one student while the others are quiet, and then to call on a different student, have one student return to their seats to have the students work in small groups.

或者，如果你更喜欢课堂教学的类比，老师可以在其他学生安静的时候点名一名学生，然后再点名另一名学生，让一名学生回到座位上，让学生分成小组。

Again, all of this by analogy, the point being that dopamine and norepinephrine are all allowing these networks to be activated to the precisely correct levels and in the precisely correct sequence.

同样，所有这些都是类推的，重点是多巴胺和去甲肾上腺素都允许这些网络被激活到精确正确的水平并以精确正确的顺序激活。

Now, the other key aspect of drugs like Adderall, Vyvanse, Ritalin, and similar to treat ADHD, has everything to do with these neuromodulators, dopamine and norepinephrine, but it has to do with their other incredible feature besides just their ability to reduce noise and increase signal within these brain networks.

现在，Adderall、Vyvanse、Ritalin 等治疗多动症的药物的另一个关键方面与这些神经调节剂、多巴胺和去甲肾上腺素有关，但除了减少大脑网络中的噪音和增加信号的能力之外，还与它们的其他令人难以置信的功能有关。

And that incredibly important feature is what we call neuroplasticity, or the brain and nervous system's ability to change in response to experience.

这个极其重要的特征就是我们所说的神经可塑性，或者大脑和神经系统根据经验而改变的能力。

I've done entire episodes of the Huberman Lab podcast on neuroplasticity, what it is, and how to access it at different stages of development and in adulthood.

我已经完成了胡伯曼实验室播客的整集，内容涉及神经可塑性、它是什么以及如何在不同的发展阶段和成年期访问它。

By the way, you can find those episodes at hubermanlab.com by simply searching plasticity in the search function.

顺便说一句，您只需在搜索功能中搜索可塑性即可在 hubermanlab.com 上找到这些剧集。

But the important thing to understand about plasticity in the context of today's discussion is that while there are many different ways to induce neuroplasticity, almost all of them involve strongly activating certain brain networks, and in that case, also strong or elevated release of certain neuromodulators.

但在今天讨论的背景下，理解可塑性的重要一点是，虽然有许多不同的方法来诱导神经可塑性，但几乎所有方法都涉及强烈激活某些大脑网络，在这种情况下，还涉及某些神经调节剂的强烈或升高的释放。

Now, we've talked about dopamine and norepinephrine.

现在，我们讨论了多巴胺和去甲肾上腺素。

They are but two of many neuromodulators.

它们只是众多神经调节剂中的两种。

Others include serotonin, acetylcholine, and each of the neuromodulators does different things at different synapses in the brain, and there's some global statements that can be made about each of them.

其他包括血清素、乙酰胆碱，每种神经调节剂在大脑的不同突触中发挥不同的作用，并且可以对它们中的每一种进行一些全局陈述。

We made some of those earlier, like dopamine is broadly involved in motivation, craving, and pursuit, and norepinephrine in signal detection and drawing of focus or salience to something in our environment or in our body or inner experience.

我们之前做了一些研究，比如多巴胺广泛参与动机、渴望和追求，去甲肾上腺素参与信号检测以及对我们环境、身体或内在体验中的某些事物进行聚焦或突出。

Serotonin does other things, acetylcholine does other things.

血清素还有其他作用，乙酰胆碱也有其他作用。

But what's really important to understand is that any time there is a dramatic elevation in dopamine and norepinephrine relative to baseline, relative to what was happening with dopamine and norepinephrine just prior to that, that has a tendency to promote neuroplasticity at particular synapses.

但真正重要的是要理解，每当多巴胺和去甲肾上腺素相对于基线显着升高时，相对于在此之前发生的多巴胺和去甲肾上腺素，就会有促进特定突触神经可塑性的趋势。

So here's where it's appropriate to remind everybody that neuromodulators are different than neurotransmitters.

因此，在这里有必要提醒大家，神经调节剂与神经递质不同。

Neurotransmitters are chemicals that, just like dopamine and norepinephrine, are released between neurons, and they are what actually contribute to the electrical signals going up or down between different neurons.

神经递质是一种化学物质，就像多巴胺和去甲肾上腺素一样，在神经元之间释放，它们实际上有助于不同神经元之间电信号的上升或下降。

And again, dopamine and norepinephrine modulate that activity, causing a given amount of neurotransmitter to have an even greater effect, for instance.

例如，多巴胺和去甲肾上腺素再次调节这种活动，导致一定量的神经递质产生更大的效果。

So when we hear about dopamine and norepinephrine and we hear about motivation or focus, et cetera, that's all fine and good, but it's also important to remember that when dopamine and norepinephrine are increased, there is a higher probability of strengthening connections where dopamine and norepinephrine are increased.

因此，当我们听到多巴胺和去甲肾上腺素以及动机或注意力等时，这一切都很好，但同样重要的是要记住，当多巴胺和去甲肾上腺素增加时，在多巴胺和去甲肾上腺素增加的地方加强联系的可能性更高。

And what that means is that later, even if levels of dopamine and norepinephrine are not increased, if they go back to baseline, it's often the case that if in our prior history or the history of a given set of neurons in our brain, there was more dopamine or norepinephrine around, it's very likely that the connections where that took place are strengthened and therefore more easily activated.

这意味着，即使多巴胺和去甲肾上腺素的水平没有增加，如果它们回到基线，通常的情况是，如果在我们之前的历史或我们大脑中一组给定神经元的历史中，周围存在更多的多巴胺或去甲肾上腺素，那么发生这种情况的连接很可能会得到加强，因此更容易被激活。

And this takes us back to the really original purpose of prescribing these sympathomimetic stimulants to children with ADHD during development.

这让我们回到了给发育期间的多动症儿童开这些拟交感神经兴奋剂的真正初衷。

It was, yes, designed to try and help them focus, to reduce their hyperactivity and help them focus.

是的，它的目的是试图帮助他们集中注意力，减少他们的多动症并帮助他们集中注意力。

But it was also designed to help the brain networks that are responsible for focus to undergo neuroplasticity.

但它也旨在帮助负责集中注意力的大脑网络实现神经可塑性。

That is, for the synapses involved to strengthen so that those networks could function more efficiently later on, even after cessation of the drug.

也就是说，所涉及的突触得到加强，以便这些网络以后能够更有效地发挥作用，即使在停药后也是如此。

This is an absolutely crucial point that I think is not often discussed when people, for instance, say, "Should I put my kid on ADHD meds?" Or, "Should I take my kid off of ADHD meds as they transition from adolescence to their later teen years and into college?" I mean, after all, no child or parent, or adult for that matter, wants to achieve a bunch of benefits with a drug and then lose those benefits later.

这是一个绝对关键的一点，我认为当人们问“我应该让我的孩子服用多动症药物吗？”时，人们不会经常讨论这一点。或者，“当我的孩子从青春期过渡到青少年后期并进入大学时，我应该停止服用多动症药物吗？”我的意思是，毕竟，没有哪个孩子、父母或成年人希望通过药物获得一系列好处，然后又失去这些好处。

Nor does any parent or child want to take a drug that they don't need to take when they could access other routes to improving the neural circuitry or the function of some health system in the body, because I don't think anyone really wants to medicate their kids unless they have to.

当父母或孩子可以通过其他途径来改善神经回路或体内某些健康系统的功能时，也没有任何父母或孩子愿意服用他们不需要服用的药物，因为我认为除非迫不得已，否则没有人真的愿意给他们的孩子用药。

I would hope not.

我希望不会。

And I don't think any kid wants to be medicated unless they absolutely need to be medicated.

我认为任何孩子都不想接受药物治疗，除非他们绝对需要接受药物治疗。

So increasing dopamine and norepinephrine with these drugs like Adderall, Vyvanse, Ritalin, and similar, is causing several things, and some of those things actually provide some general answers as to whether or not parents should put their kids on these compounds in the first place.

因此，使用阿得拉（Adderall）、维凡斯（Vyvanse）、利他林（Ritalin）等药物增加多巴胺和去甲肾上腺素会导致一些问题，其中一些问题实际上为父母是否应该首先让孩子服用这些化合物提供了一些一般性答案。

Obviously, they're going to do that under the careful consult of a qualified psychiatrist, I would hope, and only under those circumstances.

显然，我希望他们会在合格的精神科医生的仔细咨询下这样做，而且只有在这种情况下。

But also whether or not the child should stay on those drugs over time.

还有孩子是否应该长期服用这些药物。

And here's what we do know for sure.

这是我们确实知道的。

I did a vast search within the literature in order to arrive at what is very clear, which is that children with ADHD, true ADHD, who are diagnosed with ADHD and are treated with appropriate doses of drugs like Adderall, Ritalin, or Vyvanse, fare far better both in childhood and later in life when it comes to performance in school, performance in terms of focusing on anything, and in terms of general outcomes.

我在文献中进行了广泛的搜索，以获得非常明确的结论，即患有注意力缺陷多动症（真正的注意力缺陷多动症）的儿童，如果被诊断患有注意力缺陷多动症，并接受适当剂量的药物（如阿得拉、利他林或维万斯）治疗，无论是在童年时期还是在以后的生活中，无论是在学校表现、在专注于任何事情方面的表现还是在总体结果方面，都表现得更好。

So, for instance, a lot of people have wondered and worried about whether or not treatment with these drugs early in life will set up a predisposition for illicit drug abuse or craving an addictive potential later.

例如，许多人想知道并担心在生命早期接受这些药物治疗是否会产生非法药物滥用的倾向或日后渴望成瘾的可能性。

And it is very clear from the studies that have emerged over the last really 15 years, but mainly within the last five years, because that's when most of the data have arrived, that children with ADHD who are not treated correctly, both with drugs and behavioral treatments, because really the combination of drugs and behavioral treatments is the optimal situation.

从过去15年的研究中可以清楚地看出，但主要是在过去五年内，因为大多数数据都是在那时得出的，患有多动症的儿童没有得到正确的治疗，无论是药物还是行为治疗，因为实际上药物和行为治疗的结合才是最佳情况。

So kids with ADHD who are not treated with drugs and behavioral treatments to deal with their ADHD have a much higher tendency towards illicit drug use and addictive drug potential in their adulthood.

因此，患有多动症的孩子如果没有接受药物和行为治疗来治疗多动症，他们在成年后更容易使用非法药物和成瘾药物。

Okay?

好的？

So there is a real danger to not treating ADHD during childhood.

因此，在儿童时期不治疗多动症确实存在危险。

And the reverse is also true, which is that children with ADHD who take prescription drugs that are sympathomimetics, so yes, as you've heard, they are speed.

反之亦然，患有多动症的儿童服用拟交感神经药的处方药，所以是的，正如你所听到的，它们是速度。

Amphetamine is speed, although I should say if they take methylphenidate, Ritalin or Concerta or something of that sort, that's not amphetamine.

安非他明是速度，尽管我应该说如果他们服用哌醋甲酯、利他林或Concerta或类似的东西，那不是安非他明。

Nonetheless, it's a stimulant.

不管怎样，它是一种兴奋剂。

It's a sympathomimetic also.

这也是一种拟交感神经药。

These are kids that are taking these drugs during development, and therefore levels of dopamine, levels of norepinephrine are being increased in their brain and body.

这些孩子在发育过程中服用这些药物，因此他们大脑和身体中的多巴胺和去甲肾上腺素水平正在增加。

And you might say, "Well, wouldn't that lead to a craving for these things later in life?" And that does not appear to be the case.

你可能会说，“好吧，这不会导致以后的生活中对这些东西的渴望吗？”但事实似乎并非如此。

In fact, there's some very nice neuroimaging studies, mainly positron emission tomography studies that I'll provide a link to in the show note captions that show that early treatment with these drugs actually leads to combinations of increased dopamine transmission in the forebrain later in life at a lower level or a lower threshold, I should say, in a way that essentially says there's normalization of the circuits across time by the application of these drugs early in life.

事实上，有一些非常好的神经影像学研究，主要是正电子发射断层扫描研究，我将在节目注释标题中提供链接，这些研究表明，这些药物的早期治疗实际上会导致晚年前脑中多巴胺传输增加，处于较低水平或较低阈值，我应该说，从本质上说，通过在生命早期应用这些药物，可以使电路随着时间的推移而正常化。

Again, in the case of children that have diagnosed ADHD, I in no way, shape, or form want to imply that all children should be treated with these drugs.

再次强调，对于被诊断为多动症的儿童，我绝不是想暗示所有儿童都应该接受这些药物治疗。

That is quite clearly not going to be a good idea.

这显然不是一个好主意。

So all of this really speaks to the critical importance of getting an accurate diagnosis of ADHD.

因此，所有这些确实说明了准确诊断 ADHD 的至关重要性。

Diagnostic criteria include many things.

诊断标准包括很多内容。

In children, there are multiple, there are more than nine diagnostic criteria for each of the categories relating to impulsivity, hyperactivity, and so on.

在儿童中，与冲动、多动等相关的每个类别都有多种、九种以上的诊断标准。

So a well-qualified psychiatrist will do several things.

因此，一名合格的精神科医生会做几件事。

They will, first of all, do a careful diagnostic evaluation of a child, and in addition, one would hope that they would think about prescribing both appropriate pharmacologic treatments for ADHD, but also be aware of and prescribe the various other types of prescriptions, meaning behavioral prescriptions.

首先，他们会对孩子进行仔细的诊断评估，此外，人们会希望他们考虑为多动症开出适当的药物治疗方法，但也要了解并开出各种其他类型的处方，即行为处方。

So there are clearly certain learning tools and things that kids can do in order to improve their ability to focus and to be less impulsive that combine especially well with drug treatments, as well as new advancements in the realm of nutrition and supplementation that are constantly coming online.

因此，孩子们显然可以使用某些学习工具和事情来提高他们的注意力和减少冲动的能力，这些工具和事情与药物治疗以及不断出现的营养和补充剂领域的新进展结合得特别好。

And the best psychiatrists are going to be tuned into all of those aspects of treatment for ADHD, not just prescription drugs, but also behavioral treatments, also nutritional guidelines, also supplementation, and also updating each and all of those things as a child matures from each stage of development to the next.

最好的精神科医生将关注多动症治疗的所有这些方面，不仅仅是处方药，还有行为治疗、营养指南、补充剂，以及随着孩子从每个发展阶段到下一个发展阶段的成熟，更新所有这些内容。

Now, the other common question is: If a child has been treated with these ADHD meds during development, do they need to continue on those drugs indefinitely?

现在，另一个常见问题是：如果孩子在发育过程中接受了这些多动症药物治疗，他们是否需要无限期地继续服用这些药物？

And the short answer to this is it depends, and that can be a somewhat frustrating answer, I realize.

对此的简短回答是这取决于情况，我意识到这可能是一个有点令人沮丧的答案。

But the good news is it's something that can be assessed in a fairly straightforward way.

但好消息是它可以以相当简单的方式进行评估。

Let's recall that the use of these drugs to treat ADHD is designed to accomplish two things.

让我们回想一下，使用这些药物治疗多动症的目的是为了完成两件事。

It's designed to improve the function of those neural circuits that allow a child to focus, and it's also designed to increase the strength of those circuits to effectively teach the circuits how to learn what focus is.

它旨在改善那些让孩子集中注意力的神经回路的功能，并且还旨在增强这些回路的强度，以有效地教导神经回路如何学习注意力是什么。

In other words, these drugs are designed, in some cases, to be used and then withdrawn later because the circuits that they helped build up are functioning well.

换句话说，在某些情况下，这些药物被设计为先使用后撤回，因为它们帮助建立的回路运转良好。

In some cases, however, the circuits that underlie focus are not going to be able to function at the level required for normal, healthy life progression unless there's continued application of the drug.

然而，在某些情况下，除非持续使用药物，否则集中注意力的回路将无法达到正常、健康的生活进展所需的水平。

So how would this work in the real-world context?

那么这在现实世界中会如何运作呢？

Well, I think any child or adolescent or person younger than 25 that's taken these drugs has no doubt achieved some level of neuroplasticity of the neural circuits related to all the things we call focus.

嗯，我认为任何服用这些药物的儿童、青少年或 25 岁以下的人无疑都已经实现了与我们称之为注意力的所有事物相关的神经回路的某种程度的神经可塑性。

And I want to be very clear.

我想说得很清楚。

There's no single brain area or set of brain circuits for what I'm referring to as focus, because after all, focus involves task switching, focus involves all sorts of different cognitive operations depending on what we're focusing on.

我所说的专注并不存在单一的大脑区域或一组大脑回路，因为毕竟，专注涉及任务切换，专注涉及各种不同的认知操作，具体取决于我们所关注的内容。

Right?

正确的？

Focusing on a sport is basically a practice of directing one's attention in different locations at different moments.

专注于一项运动基本上是一种在不同时刻将注意力集中在不同位置的练习。

Focusing on studying is an entirely different pattern of focus altogether.

专注于学习是一种完全不同的专注模式。

But the point being, if a person 25 years or younger takes a drug that increases dopamine and norepinephrine and Assuming that things are working, meaning the dose is right, they're achieving better ability to focus, et cetera, those circuits are going to get stronger.

但重点是，如果一个 25 岁或更年轻的人​​服用一种增加多巴胺和去甲肾上腺素的药物，并且假设一切正常，意味着剂量正确，他们就会获得更好的专注能力，等等​​，这些回路将会变得更强。

And it seems entirely reasonable, in fact, it was supported by the psychiatrist that I spoke to prior to this episode, that people who have been on ADHD meds for any point of time prior to 25, talk to their psychiatrist about what tapering off those drugs in order to examine whether or not they still need those drugs would look like.

事实上，这似乎是完全合理的，事实上，我在本集之前采访过的精神科医生也支持这一点，即那些在 25 岁之前任何时间点服用 ADHD 药物的人，都会与他们的精神科医生讨论逐渐减少这些药物的情况，以检查他们是否仍然需要这些药物。

Now, I mention the word taper because there is a withdrawal potential of simply stopping these drugs very quickly, because they do ramp up dopamine and norepinephrine.

现在，我提到逐渐减少这个词，因为快速停止这些药物就有可能产生戒断反应，因为它们确实会增加多巴胺和去甲肾上腺素。

Even though they increase plasticity of the neural circuits for focus and mood and motivation, if one very abruptly ceases taking any of these drugs, it does not feel good.

尽管它们增加了注意力、情绪和动机的神经回路的可塑性，但如果一个人突然停止服用这些药物中的任何一种，感觉都不会好。

That drop in dopamine that one inevitably experiences is almost always associated with lethargy, with depressed mood, with feeling not good in a number of ways, and of course, challenges in focus.

一个人不可避免地经历的多巴胺下降几乎总是与昏昏欲睡、情绪低落、在很多方面感觉不好，当然还有注意力集中的挑战有关。

So anytime one is going to go off one of these drugs or sample what it is to even reduce dosage, that has to be done in close communication with a board-certified psychiatrist.

因此，任何时候当一个人想要停用其中一种药物或尝试减少剂量时，都必须与经过委员会认证的精神科医生密切沟通。

At the same time, it was made very clear to me from ADHD expert psychiatrists that reductions in dosage over time often are optimal for a patient.

与此同时，多动症专家精神科医生向我明确表示，随着时间的推移减少剂量通常对患者来说是最佳选择。

Okay?

好的？

And this gets to the whole issue of dosage generally.

这涉及到整个剂量问题。

I spent a good amount of time talking to somebody who prescribes these drugs, both to children and adults, about dosage ranges.

我花了很多时间与给儿童和成人开这些药物的人讨论剂量范围。

And I don't want to spend too much time on this from the perspective of how much one should take.

从应该花多少的角度来看，我不想在这上面花太多时间。

In fact, I don't want anyone to think that what I'm about to say should dictate what they should take specifically, because that's something that really has to be worked out on an individual basis.

事实上，我不希望任何人认为我接下来要说的内容应该决定他们具体应该采取什么措施，因为这确实需要根据个人情况来解决。

But it is worth noting that if you look at the studies on Adderall and methylphenidate, what you'll see is a pretty broad range in those studies, and that's because some of the studies used people that were already taking these drugs and asked them to participate in neuroimaging studies.

但值得注意的是，如果你看一下关于阿得拉和哌醋甲酯的研究，你会发现这些研究的范围相当广泛，这是因为有些研究使用了已经服用这些药物的人，并要求他们参与神经影像学研究。

Other studies actually put people on these drugs for the very first time or adjusted their dosage.

其他研究实际上是让人们第一次服用这些药物或调整他们的剂量。

And so you'll see a tremendous range of drug doses explored.

因此，您将看到各种药物剂量的探索。

For instance, you will see anywhere from 10 to 40 milligrams of Adderall per day.

例如，您每天会看到 10 至 40 毫克的阿得拉。

You'll see anywhere from 10 to 60 milligrams of Ritalin per day.

您每天会看到 10 至 60 毫克的利他林。

And here we could easily be talking about studies on children or adults.

在这里我们可以很容易地谈论针对儿童或成人的研究。

With respect to Vyvanse, you'll see that the dosages tend to be much higher.

对于 Vyvanse，您会发现剂量往往要高得多。

In part, that's because Vyvanse has, if you recall, it's that lysine, which is a big molecule, stuck on d-amphetamine, which is a smaller molecule.

部分原因是，如果你还记得的话，Vyvanse 是将赖氨酸（一种大分子）附着在 d-安非他明（一种较小的分子）上。

And so the dosages of Vyvanse tend to be in the hundreds of milligram ranges, but most of that 100 milligrams of Vyvanse is not going to be the d-amphetamine, it's going to be the lysine, which doesn't do anything in the context of treating the brain.

因此，Vyvanse 的剂量往往在数百毫克范围内，但这 100 毫克的 Vyvanse 中的大部分不是 d-苯丙胺，而是赖氨酸，赖氨酸在治疗大脑方面没有任何作用。

It's just there to control the slow release.

它只是为了控制缓慢释放。

So it's thought that 100 milligrams of Vyvanse translates to roughly nine milligrams of Adderall and on and on.

因此，人们认为 100 毫克的 Vyvanse 大约相当于 9 毫克的 Adderall 等等。

And actually, it's pretty hard to translate between dosages of different drugs in any direct way.

事实上，很难以任何直接的方式在不同药物的剂量之间进行转换。

And in speaking with a psychiatrist expert in ADHD in preparation for this episode, he made very clear that it is extremely difficult to predict how a child or adult will react to a given dosage of any of these drugs.

在为这一事件做准备时，在与多动症方面的精神病专家交谈时，他非常明确地表示，很难预测儿童或成人对给定剂量的这些药物的反应如何。

So much so, in fact, that he anecdotally reported to me that one of his patients is a male, 300 pounds, diagnosed with ADHD, and who achieves tremendous relief from just 2.5 milligrams of Adderall per day.

事实上，他曾向我透露，他的一位患者是一名男性，体重 300 磅，被诊断患有多动症，每天仅服用 2.5 毫克阿得拉，症状就得到了巨大缓解。

And at the same time, he has two patients, both of whom are sisters, so they're genetically related, who are in the 120 to 140 pound range, who did not respond well at all for the treatment of their ADHD until their dosages were very, very high.

与此同时，他还有两名患者，她们都是姐妹，所以她们有遗传关系，她们的体重在 120 到 140 磅之间，在剂量非常非常高之前，她们对 ADHD 的治疗根本没有很好的反应。

And if I tell you these dosages, I just want to warn you in advance, I am not suggesting anyone explore these dosages without, of course, the approval of their psychiatrist.

如果我告诉你这些剂量，我只是想提前警告你，我并不是建议任何人在没有精神病医生批准的情况下探索这些剂量。

Turns out that neither of these two young women responded at all to ADHD medication until they achieved dosages in the range of 180, in the case of one sister, and 240 milligrams, in the case of the other sister, per day, which is an astronomically high dose on the face of it.

事实证明，这两位年轻女性对多动症药物都没有任何反应，直到她们的一个姐妹的剂量达到每天 180 毫克，另一个姐妹的剂量达到每天 240 毫克，这从表面上看是一个天文数字般的高剂量。

But this physician, again, board-certified physician, expert in ADHD, verified for me that indeed, neither of them experienced any discomfort or side effects that led them to not want to take the drug.

但这位医生，再一次，委员会认证的医生，多动症专家，向我证实，确实，他们俩都没有经历过任何导致他们不想服用该药物的不适或副作用。

But of course, that amount of Adderall could send somebody else into an absolute psychotic fit, could potentially even cause cardiac arrest.

但当然，大量的阿德拉可能会让其他人陷入绝对的精神病状态，甚至可能导致心脏骤停。

It's remarkable the ranges of Adderall that are used effectively in children and adults.

值得注意的是，阿得拉在儿童和成人中的使用范围非常广泛。

And this is true for a lot of the other sympathomimetics used to treat ADHD.

对于许多用于治疗多动症的其他拟交感神经药来说也是如此。

And of course, a good psychiatrist will always assess dosage as it relates to positive benefits, relief of symptoms.

当然，优秀的精神科医生总是会评估剂量，因为它与积极的益处和症状的缓解有关。

So relief of impulsivity, relief of hyperactivity, improvements in ability to focus, and of course, they are going to consider side effects, any uncomfortable adverse effects that come from taking the drug at a given dosage or taking the drug at all.

因此，缓解冲动、缓解多动症、提高注意力集中能力，当然，他们会考虑副作用，即按给定剂量服用药物或根本服用药物所产生的任何不舒服的副作用。

Now, of course, this all begs the question of why such tremendous variation?

当然，现在这一切都引出了一个问题：为什么会有如此巨大的变化？

Is this due to genetic differences in the amount of dopamine or norepinephrine that people make?

这是由于人们产生的多巴胺或去甲肾上腺素的数量存在遗传差异吗？

It appears that the major underlying factor for why people require such vastly different dosages of these sympathomimetics for the relief of ADHD has to do with the different enzymes or levels of enzymes that people make which metabolize these drugs, both in the brain and body.

人们为什么需要如此不同剂量的拟交感神经药来缓解多动症，这似乎与人们在大脑和身体中代谢这些药物所产生的不同酶或酶水平有关。

And unfortunately, there is no simple blood test or saliva test or test of any kind that can predict how someone will respond to these drugs.

不幸的是，没有简单的血液测试或唾液测试或任何类型的测试可以预测某人对这些药物的反应。

So the most logical and safe way to assess dosage is to start with the lowest Possible effective dose and to increase only as necessary in order to achieve the positive benefits, while, of course, paying attention to any side effects that might arise.

因此，评估剂量的最合乎逻辑和最安全的方法是从尽可能低的有效剂量开始，并仅在必要时增加剂量，以实现积极的效果，同时当然要注意可能出现的任何副作用。

A question that comes up from time to time when discussing the long-term effects of drugs like Adderall, Ritalin, and Vyvanse is whether or not they can negatively impact height or growth or development in some other way.

在讨论阿得拉、利他林和 Vyvanse 等药物的长期影响时，不时出现的一个问题是它们是否会以其他方式对身高、生长或发育产生负面影响。

This is a logical question to ask because, after all, these drugs are effectively mimicking stress in the body.

这是一个合乎逻辑的问题，因为毕竟这些药物可以有效地模拟体内的压力。

And most everyone has heard by now that while stress can help us in the short term, it helps us deploy immune molecules to protect us against infection, it sharpens our visual focus and our ability to respond to things for survival.

现在大多数人都听说过，虽然压力可以在短期内帮助我们，但它可以帮助我们部署免疫分子来保护我们免受感染，它可以增强我们的视觉焦点和我们对生存做出反应的能力。

Chronically elevating our stress over long periods of time, we know reduces the effectiveness of our immune system and can actually cause certain forms of brain degeneration.

我们知道，长期长期增加压力会降低免疫系统的有效性，实际上会导致某些形式的大脑退化。

And while there aren't a lot of longitudinal studies on the heights of kids with ADHD, and of course, we never can tell how tall someone would have grown to be if they were treated with a drug because we don't have a perfect control experiment, even in the case of identical twin experiments, and therein, there aren't that many of those examples where one twin was treated for ADHD and the other wasn't, et cetera.

虽然关于患有多动症的孩子身高的纵向研究并不多，当然，我们永远无法判断一个人如果接受药物治疗会长到多高，因为我们没有完美的对照实验，即使是在同卵双胞胎实验中，而且其中一个双胞胎接受多动症治疗而另一个没有接受治疗的例子并不多，等等。

But here's what we know.

但这就是我们所知道的。

It does not appear that treatment with sympathomimetics during development, provided the dosages are kept in the appropriate ranges, is going to limit overall height.

如果剂量保持在适当的范围内，在发育过程中使用拟交感神经药治疗似乎不会限制整体身高。

In fact, if you look at the data, it appears that children with ADHD who are treated with ADHD meds actually arrive at slightly higher BMIs, body mass indexes, compared to age-matched peers.

事实上，如果你看一下数据，就会发现，与同龄同龄人相比，接受 ADHD 药物治疗的 ADHD 儿童的 BMI（体重指数）实际上略高。

Now, of course, body mass index doesn't necessarily correlate with height, right?

当然，体重指数不一定与身高相关，对吧？

Someone could not achieve a full height but could be heavier, either through bone or fat or muscle or a combination of all three.

有些人无法达到完整的高度，但可以通过骨骼、脂肪、肌肉或三者的组合而变得更重。

But what we know is that the appropriate use of ADHD meds during development is not stunting development in any kind of overall way.

但我们知道，在发育过程中适当使用多动症药物不会以任何方式阻碍发育。

It's not preventing maturation of the body in ways that are leading to reduced weight or somehow impaired growth overall.

它并不会阻止身体成熟，从而导致体重减轻或整体生长受损。

With that said, long-term elevations of sympathetic nervous system activity does carry some risk.

话虽如此，交感神经系统活动的长期升高确实会带来一些风险。

And one of the primary risks that people have wondered about is cardiovascular risk.

人们想知道的主要风险之一是心血管风险。

And this makes perfect sense, right?

这很有道理，对吧？

When you increase the activity of the sympathetic nervous system, you increase blood pressure, you increase heart rate, you increase, in some cases, peripheral sweating, all the things that we associate with stress.

当交感神经系统的活动增加时，血压就会升高，心率会加快，在某些情况下还会增加末梢出汗，所有这些都与压力有关。

So you can imagine that a child or adult with ADHD that takes these sympathomimetics every day, even if the dosage is kept in a range that doesn't allow them to experience any immediate untoward side effects, so they're not feeling miserable, they're just feeling like they can focus better.

所以你可以想象一个患有注意力缺陷多动症的儿童或成人每天服用这些拟交感神经药，即使剂量保持在一个不会让他们立即出现任何不良副作用的范围内，所以他们不会感到痛苦，他们只是觉得自己可以更好地集中注意力。

But one always wonders what's going on under the hood, so to speak.

但可以这么说，人们总是想知道幕后发生了什么。

There is, as far as I know, one major study that's addressed this, and the conclusions of that study were a little bit hard to put into a single category.

据我所知，有一项主要研究解决了这个问题，该研究的结论有点难以归入单一类别。

It did point to a subtle increase in cardiovascular risk, but the results did not point to anything so dramatic that the authors of the study warned against taking these drugs or encouraging people to cease taking these drugs, again, provided they're being prescribed by a board-certified physician for ADHD and at the appropriate dosage for that person.

它确实表明心血管风险略有增加，但结果并没有表明任何戏剧性的事情，以至于该研究的作者再次警告不要服用这些药物或鼓励人们停止服用这些药物，前提是这些药物是由经过委员会认证的多动症医生开出的，并且剂量适合该人。

That said, I think this all, again, speaks to the importance of arriving at minimal effective dosage.

也就是说，我认为这一切再次说明了达到最低有效剂量的重要性。

And it stands to reason that if you're somebody who's taking ADHD meds or if your child is taking ADHD meds, that one would want to do all the other things that they could do in order to try and improve cardiovascular health or at least not put it at additional risk.

按理说，如果您正在服用多动症药物，或者您的孩子正在服用多动症药物，那么您会想要做所有他们可以做的其他事情，以尝试改善心血管健康，或者至少不使其面临额外的风险。

So those are going to be the obvious things like avoiding smoking or vaping nicotine.

所以这些都是显而易见的事情，比如避免吸烟或吸尼古丁。

Regular exercise is going to be encouraged and things of that sort.

将鼓励定期锻炼之类的事情。

And that dovetails into a bunch of other questions that are often asked any time the topic of Adderall or Ritalin comes up, which is, what about alcohol?

这与每当提到阿得拉或利他林的话题时经常被问到的一系列其他问题相吻合，那就是，酒精怎么样？

Is drinking alcohol at the same time or at different times even going to be problematic if one is taking these drugs?

如果服用这些药物，同时或不同时间饮酒是否会出现问题？

Is taking benzodiazepines going to be a problem, et cetera?

服用苯二氮卓类药物会成为问题吗？

There's a very straightforward answer to this, which is, it's very clear that alcohol, certainly in children, but also in adults, is best not consumed.

对此有一个非常直接的答案，那就是，很明显，最好不要饮酒，尤其是儿童，而且成人也是如此。

I did an entire episode about alcohol, which got into this and the data for this.

我做了一整集关于酒精的节目，其中涉及到这个和这个的数据。

If you've heard that having some alcohol, in particular red wine, is better for you than no alcohol, that is simply not true.

如果您听说喝点酒，尤其是红酒，比不喝酒对身体更好，那根本不是事实。

Sorry, it's not true.

抱歉，这不是真的。

Most adults who are not alcoholics can probably have up to two, that's right, two drinks per week and still be on the safe side of health, although zero is better than two.

大多数不酗酒的成年人可能每周最多喝两杯，没错，喝两杯，并且仍然保持健康安全，尽管零比两杯要好。

And once you get past two, you start seeing effects on various systems, including increased cancer risk, especially brain neuron loss and degeneration risk.

一旦超过两个，您就会开始看到对各种系统的影响，包括癌症风险增加，尤其是脑神经元损失和退化风险。

I covered all of those data in the episode on alcohol that you can find at hubermanlab.com.

我在有关酒精的一集中介绍了所有这些数据，您可以在 hubermanlab.com 上找到这些数据。

Combining alcohol with sympathomimetics, even though they reside in very different pathways within the brain, in fact, the sympathomimetics are driving up sympathetic nervous system activity, whereas alcohol is actually doing the opposite.

将酒精与拟交感神经药结合起来，尽管它们存在于大脑内非常不同的通路中，但事实上，拟交感神经药正在推动交感神经系统的活动，而酒精实际上起着相反的作用。

It's depressing it.

真是郁闷啊

And yet all the data point to the fact that combining alcohol with sympathomimetics such as Vyvanse, Adderall, Ritalin, or any kind of amphetamine is going to be more detrimental to the brain and body than simply taking those drugs on their own.

然而所有的数据都表明，将酒精与拟交感神经药（如 Vyvanse、Adderall、利他林或任何一种安非他明）结合使用，对大脑和身体的危害比简单地单独服用这些药物更大。

Put differently and more directly, if you are taking any of the drugs that we've been talking about to treat ADHD, or if you just happen to be taking them for whatever reason, you are going to want to avoid drinking alcohol at any time, and you're going to want to avoid benzodiazepines and similar, unless they've been prescribed to you by your physician.

换句话说，更直接地说，如果您正在服用我们一直在谈论的任何治疗多动症的药物，或者您只是出于某种原因正在服用这些药物，那么您将需要随时避免饮酒，并且您将需要避免使用苯二氮卓类药物和类似药物，除非您的医生给您开了这些药物。

In advance of this episode, I put a call out on social media for questions about Adderall, et cetera, and I got a lot of questions about whether or not there are impacts of these drugs on the hormone systems of the body, and if they impact the reproductive system in particular.

在这一集之前，我在社交媒体上呼吁人们询问有关阿得拉等的问题，我收到了很多关于这些药物是否对身体激素系统有影响，以及它们是否特别影响生殖系统的问题。

I also got questions about whether or not these drugs impact sexual behavior or libido or anything of that sort.

我还被问到这些药物是否会影响性行为或性欲或类似的东西。

In reviewing the literature, what I can tell you is that there are very few studies, unfortunately, of the long-term effects of these drugs on the endocrine or hormone systems of the body.

不幸的是，在回顾文献时，我可以告诉你的是，关于这些药物对身体内分泌或激素系统的长期影响的研究很少。

But we do know a few things for sure.

但我们确实知道一些事情。

First of all, when you increase the activity of the sympathetic nervous system for long periods of time, you are very likely increasing levels of cortisol.

首先，当你长时间增加交感神经系统的活动时，你很可能会增加皮质醇的水平。

Cortisol is a "stress hormone," but cortisol also plays some really important positive roles in your body.

皮质醇是一种“压力荷尔蒙”，但皮质醇还在您的身体中发挥着一些非常重要的积极作用。

In fact, you want cortisol released, especially early in the day.

事实上，您希望释放皮质醇，尤其是在一天的早些时候。

You don't want cortisol released so much late in the day.

你不希望皮质醇在一天的晚些时候释放得如此之多。

This actually relates back to timing and schedules of taking drugs.

这实际上与服药的时间和时间表有关。

This is something, again, that needs to be worked out with your psychiatrist or your child's psychiatrist.

同样，这需要与您的精神科医生或您孩子的精神科医生一起解决。

But one of the reasons why there are so many different drugs for the treatment of ADHD is that each and all of them has a different time course of action.

但治疗多动症的药物如此之多的原因之一是，每种药物都有不同的作用时间。

So Ritalin is very short-lived, which might sound bad because then you have to take it multiple times throughout the day.

所以利他林的作用非常短暂，这可能听起来很糟糕，因为你必须在一天中多次服用它。

But if you think about from the perspective of sleep and the importance of having low cortisol at night, and these drugs increase cortisol, and the importance of getting sleep, because after all, sleep is the foundation of mental health, physical health, and performance in kids and adults.

但如果你从睡眠的角度考虑，以及夜间皮质醇水平较低的重要性，而这些药物会增加皮质醇，以及睡眠的重要性，因为毕竟，睡眠是儿童和成人心理健康、身体健康和表现的基础。

It's responsible for growth.

它负责增长。

It's when neuroplasticity happens.

这是神经可塑性发生的时候。

It's just so vitally important.

这实在是太重要了。

A lot of the drugs that we've been talking about can severely limit one's ability to fall and stay asleep.

我们一直在谈论的许多药物都会严重限制一个人入睡和保持睡眠的能力。

And so a short-acting drug like Ritalin is actually attractive from the perspective of being able to take it in the morning and still get to sleep at night, or taking it in the morning and in the afternoon, and maybe even again in the evening, depending on the person, and then still being able to fall asleep at night.

因此，像利他林这样的短效药物实际上很有吸引力，因为它可以早上服用，晚上仍然可以入睡，或者早上和下午服用，甚至晚上再服用一次，这取决于个人，然后晚上仍然可以入睡。

Whereas long-duration release of d-amphetamine, which is what you get when you take Vyvanse, for some people, is going to inhibit their sleep.

然而，对于某些人来说，服用 Vyvanse 时会长时间释放 d-苯丙胺，这会抑制他们的睡眠。

They'll get a nice, steady rise and improvement in focus and reduction in hyperactivity, but they might have a lot of trouble falling asleep at night.

他们的注意力会得到良好、稳定的提高和改善，多动现象也会减少，但他们在晚上可能会很难入睡。

And Adderall, having a somewhat intermediate time course of action between Ritalin, which is short-lived, and Vyvanse, which is very long-lived, perhaps is going to be the best solution for somebody else, where they can take it early in the day, perhaps at a low dose, maybe again later in the day, low dose, and then still fall asleep at night.

Adderall 的作用时间介于短暂的利他林和非常长效的 Vyvanse 之间，也许对其他人来说是最好的解决方案，他们可以在白天早些时候服用，也许以低剂量，也许在当天晚些时候再次服用，低剂量，然后在晚上仍然可以入睡。

But I've spoken to people, and I spoke to this clinician expert in ADHD, who told me that some people will take as little as 2.5 milligrams of Adderall at 6:00 a.m.

但我和人们交谈过，我和这位多动症临床专家交谈过，他告诉我，有些人会在早上 6:00 服用仅 2.5 毫克的阿得拉 (Adderall)。

and have a hard time falling asleep later that night at 11:00 p.m.

那天晚上 11:00 很难入睡。

So again, vastly different sensitivities to these drugs, leading to vastly different requirements of dosage and timing of intake and which particular drug somebody might choose to or choose not to take.

同样，对这些药物的敏感性差异很大，导致对剂量和服用时间的要求以及人们可能选择服用或选择不服用哪种特定药物的要求差异很大。

So how does that relate to hormones and sex and reproduction?

那么这与激素、性和生殖有何关系呢？

Well, cortisol itself is a hormone.

嗯，皮质醇本身就是一种激素。

It can act as a bit of a hormone and a neurotransmitter in the brain.

它可以充当大脑中的一种激素和神经递质。

But for the most part, it's acting as a hormone in the brain and body, and it does a number of things.

但在大多数情况下，它在大脑和身体中充当一种激素，并且有很多作用。

First of all, it can enhance your levels of focus and alertness.

首先，它可以提高你的注意力和警觉性。

It can activate your immune system.

它可以激活你的免疫系统。

I know the immunologists out there just cringe when I say activate the immune system.

我知道当我说激活免疫系统时，免疫学家们会感到畏缩。

Your immune system is always doing various things, so it's always active, just as your nervous system is always active.

您的免疫系统始终在做各种事情，因此它始终处于活跃状态，就像您的神经系统始终处于活跃状态一样。

But to be specific, it can amplify or mobilize the release of anti-inflammatory molecules in your brain and body to combat different types of bacterial, viral, and fungal infections.

但具体来说，它可以放大或动员大脑和身体中抗炎分子的释放，以对抗不同类型的细菌、病毒和真菌感染。

It's doing an enormous number of positive things.

它正在做大量积极的事情。

It's also involved in setting mood.

它还涉及调节情绪。

It has interactions with thyroid hormone pathways.

它与甲状腺激素途径有相互作用。

I've done entire episodes about cortisol and cortisol regulation.

我已经完成了有关皮质醇和皮质醇调节的整集。

To paint all of that with a very broad brush and briefly now, it's advantageous to have your cortisol release high in the early part of the day and to taper off toward the end of the day.

现在用大笔简单地描绘所有这些，让你的皮质醇在一天的早些时候释放大量并在一天结束时逐渐减少是有利的。

In fact, late day elevations in cortisol are a strong correlate of depressive symptoms.

事实上，白天皮质醇的升高与抑郁症状有很强的相关性。

This was demonstrated by my colleagues David Spiegel and Robert Sapolsky at Stanford School of Medicine.

我在斯坦福大学医学院的同事戴维·斯皮格尔（David Spiegel）和罗伯特·萨波尔斯基（Robert Sapolsky）证明了这一点。

But that is not to say that cortisol is bad.

但这并不是说皮质醇不好。

It's to say that the timing of cortisol release is key.

这就是说，皮质醇释放的时机是关键。

So do these sympathomimetic drugs disrupt the endocrine system?

那么这些拟交感神经药会扰乱内分泌系统吗？

Well, they can.

嗯，他们可以。

If you are very awake and very alert, regardless of whether or not you're taking your sympathomimetic treatment for ADHD early in the day or late in the day, you are very likely experiencing elevations in cortisol late in the day.

如果您非常清醒且警觉，无论您是否在当天早些时候或当天晚些时候接受拟交感神经治疗多动症，您很可能会在当天晚些时候经历皮质醇升高。

So it is important, even for those of you that like to study and need to focus in the evening and nighttime hours, that you try and limit your levels of overall alertness and certainly stress late in the day, because doing that day after day after day for several weeks or months or years can indeed disrupt other hormones in the endocrine system.

因此，即使对于那些喜欢学习、需要在晚间和夜间集中注意力的人来说，尝试限制自己的整体警觉性水平和在一天晚些时候的压力也很重要，因为日复一日、持续数周、数月或数年的这样做确实会扰乱内分泌系统中的其他激素。

And again, that's because cortisol is interacting with thyroid hormone and testosterone and estrogen.

再说一遍，这是因为皮质醇与甲状腺激素、睾酮和雌激素相互作用。

In fact, cortisol in many ways competes with or can outcompete for the production of testosterone and other so-called steroid hormones.

事实上，皮质醇在许多方面与睾酮和其他所谓类固醇激素的产生竞争或可能胜过睾酮和其他所谓的类固醇激素。

Remember, cortisol itself is a corticosteroid hormone.

请记住，皮质醇本身是一种皮质类固醇激素。

So when we hear the word steroids, oftentimes people just think about athletes and steroid abuse in sports.

因此，当我们听到类固醇这个词时，人们通常只会想到运动员和运动中类固醇的滥用。

But steroid hormones includes a lot of different types of hormones, which are good for us.

但类固醇激素包括许多不同类型的激素，这些激素对我们都有好处。

Our endogenous steroid hormones are vital for all sorts of things, vitality, reproduction, et cetera.

我们的内源性类固醇激素对于各种事物、活力、繁殖等都至关重要。

And the way this works, in general terms, is that the cholesterol molecule is used to create testosterone and cortisol and estrogen.

一般来说，其工作原理是胆固醇分子被用来产生睾酮、皮质醇和雌激素。

If we make too much cortisol, we, in many ways, are reducing the total amount of testosterone that we make or that is active.

如果我们产生过多的皮质醇，我们就会在很多方面减少我们产生的或活跃的睾酮总量。

It's not Exactly that straightforward, but we can make that statement with confidence.

事情并不那么简单，但我们可以充满信心地做出这样的声明。

For instance, if you spike your cortisol just briefly during the day because you have some sort of stressful event, that's not going to inhibit your testosterone.

例如，如果你在白天因为某种压力事件而短暂地升高皮质醇，这不会抑制你的睾丸激素。

In fact, it probably is going to boost your testosterone levels somewhat.

事实上，它可能会在一定程度上提高你的睾丸激素水平。

However, if your cortisol levels are chronically elevated, yes, indeed, it's likely that you're going to suppress your total and/or free unbound forms of testosterone, and downstream to that, you will experience effects such as reductions in libido, reductions in muscle and bone mass, reductions in all sorts of aspects of testosterone-related psychology and bodily biology.

然而，如果你的皮质醇水平长期升高，是的，确实，你很可能会抑制你的总睾酮和/或游离未结合形式的睾酮，而在其下游，你会经历诸如性欲降低、肌肉和骨质减少、与睾酮相关的心理和身体生物学各方面降低等影响。

This is true for both males and females, and the same thing could be said for estrogen.

对于男性和女性来说都是如此，雌激素也是如此。

Now, what's impossible for us to say is whether or not taking a given treatment for ADHD is going to, for instance, prevent a woman from ovulating.

现在，我们不可能说的是，采取某种治疗多动症的方法是否会阻止女性排卵。

That could happen through chronic elevations in cortisol, but there's no direct link, meaning there are no studies, at least that I'm aware of, showing that people that take Adderall have irregular ovulatory cycles or that they cease menstruating entirely.

这可能是通过皮质醇的慢性升高而发生的，但没有直接的联系，这意味着没有研究，至少据我所知，表明服用阿得拉的人有不规则的排卵周期或完全停止月经。

I don't think there's any evidence for that whatsoever, nor is there any evidence that people that take Adderall or other sympathomimetics for the treatment of ADHD have lower overall testosterone.

我认为没有任何证据表明这一点，也没有任何证据表明服用阿得拉或其他拟交感神经药治疗多动症的人总体睾酮水平较低。

In fact, you can imagine all sorts of instances in which the opposite was true, that a child or young adult or adult who has ADHD but then goes on these meds to improve their symptoms is now focusing and achieving more in life.

事实上，你可以想象各种相反的情况，一个患有多动症的儿童、年轻人或成年人，但后来通过服用这些药物来改善症状，现在可以集中注意力并在生活中取得更多成就。

We know that happiness can impact dopamine and vice versa, and testosterone levels and productivity itself, and reaching our goals can feed back on the hormone system.

我们知道幸福会影响多巴胺，反之亦然，睾酮水平和生产力本身也会影响，而实现我们的目标可以反馈给激素系统。

So anytime there's a discussion about hormones or a study that shows that doing X or not doing Y impacts hormone levels of a given type, we have to be very careful to make sure that we're talking about causality because all of these hormones are in a very intricate crosstalk with one another.

因此，每当有关于激素的讨论或一项研究表明做 X 或不做 Y 会影响特定类型的激素水平时，我们都必须非常小心，以确保我们正在谈论因果关系，因为所有这些激素都处于非常复杂的相互影响中。

We can, however, make a very general statement, which is that when you are in states of stress for long periods of time, that is not a favorable condition for your immune system, your hormone system, or frankly, any other system in the brain and body.

然而，我们可以做一个非常笼统的说法，那就是，当你长时间处于压力状态时，这对你的免疫系统、激素系统，或者坦率地说，对大脑和身体的任何其他系统都不是一个有利的条件。

So the treatment of ADHD with these drugs should never be done at the expense of these other critical biological systems.

因此，用这些药物治疗多动症绝不应该以牺牲其他重要的生物系统为代价。

Another common question and concern is whether or not kids, and I suppose for that matter, adults, that take medication for ADHD are basically being predisposed to psychosis and/or other forms of addiction.

另一个常见的问题和担忧是，服用多动症药物的儿童（我想是成年人）是否基本上容易患上精神病和/或其他形式的成瘾。

And earlier, we talked a bit about the risk for addiction and the take-home message there is very clear that kids and adults that are treated for ADHD appropriately, so with the appropriate dosage of the appropriate drugs under the supervision of a board-certified qualified psychiatrist, are at less risk for forming addictions to other substances in adulthood or other substances generally.

早些时候，我们讨论了一些成瘾的风险和带回家的信息，很明显，接受适当多动症治疗的儿童和成人，因此在经过委员会认证的合格精神科医生的监督下使用适当剂量的适当药物，在成年后或一般情况下对其他物质形成成瘾的风险较小。

I think a lot of people also wonder whether or not those kids and those adults that take these ADHD meds become addicted to the medications themselves.

我想很多人也想知道服用这些多动症药物的孩子和成年人是否会对药物上瘾。

It's a bit of a tricky issue to resolve.

这是一个需要解决的有点棘手的问题。

Anytime one stops taking a drug or even tapers off a drug that's used to treat something where they feel better on the drug, they are going to experience two sets of effects, and these two sets of effects are often confounded with one another.

每当一个人停止服用药物，甚至逐渐减少用于治疗某种药物而感觉更好的药物时，他们都会经历两组效应，而这两组效应常常相互混淆。

One is the withdrawal effects, so the effects of removing the drug that makes somebody feel less good than baseline.

一是戒断效应，即戒断药物后让人感觉不如基线的效应。

So for instance, a kid that takes ADHD meds until their late teens or early 20s decides they're going to taper off.

举例来说，一个孩子在十几岁或二十岁出头时一直服用治疗多动症的药物，并决定逐渐减少剂量。

They do that, and they're feeling lousy during the taper, or when they reduce their dosage to zero, they're foggy brain, they can't focus, they feel a little bit depressed mood.

他们这样做了，在减量期间他们感觉很糟糕，或者当他们将剂量减少到零时，他们的大脑变得模糊，他们无法集中注意力，他们感到情绪有点沮丧。

It's unclear whether or not those are withdrawal symptoms or whether or not those are the consequence of not having the systems in their brain activated the way that those systems were activated before.

目前还不清楚这些是否是戒断症状，​​或者是否是由于大脑中的系统没有像以前那样激活的结果。

I realize that for some of you, that might seem like the same thing, but that's not necessarily the same thing.

我意识到对于你们中的一些人来说，这可能看起来是同一件事，但不一定是同一件事。

And probably the best analogy would be something along the lines of a hangover, right?

也许最好的类比就是宿醉，对吧？

If somebody drinks too much on a given night, the next morning, they have a hangover.

如果有人在某一晚喝得太多，第二天早上，他们就会宿醉。

The hangover makes them feel lousy.

宿醉让他们感觉很糟糕。

It is actually a withdrawal from alcohol effect.

这实际上是一种戒酒效应。

But then when they recover from the hangover, they realize that their sober state, it feels pretty good.

但当他们从宿醉中恢复过来时，他们发现自己清醒的状态，感觉还不错。

It doesn't obviously feel the same as being on alcohol, but that sober state is not a state of withdrawal.

明显感觉和喝酒不一样，但清醒状态并不是戒断状态。

Okay, if we were to look at removal or tapering off of ADHD meds, there's going to be a period of withdrawal symptoms, but then the real question is, how does somebody feel after they get through those withdrawal symptoms?

好吧，如果我们要考虑去除或逐渐减少多动症药物，就会有一段时间的戒断症状，​​但真正的问题是，人们在经历了这些戒断症状后感觉如何？

So that's an important issue to highlight.

所以这是一个需要强调的重要问题。

Now, in terms of psychosis, this is a very interesting and very important literature.

现在，就精神病而言，这是一篇非常有趣且非常重要的文献。

First of all, any amphetamine, whether or not it's d-amphetamine, L-amphetamine, and also methylphenidate for that matter, Ritalin, can induce psychosis.

首先，任何安非他明，无论是d-安非他明、L-安非他明，还是哌醋甲酯、利他林，都可能诱发精神病。

Now, there are a number of different factors that are going to predispose somebody to psychosis.

现在，有许多不同的因素会使人容易患上精神病。

Having a first relative who's had psychotic episodes, either schizophrenic episodes or bipolar episodes, is certainly a strong predisposition.

有一个患有精神病发作的第一亲属，无论是精神分裂症发作还是双相情感障碍发作，无疑是一种强烈的倾向。

Of course, if an individual themselves have had psychotic episodes, that's the strongest predisposition that one could imagine.

当然，如果一个人本身患有精神病，那么这是人们可以想象的最强烈的倾向。

So having a first relative with schizophrenia or with bipolar depression, or it's sometimes called bipolar disorder, sometimes it's also just called bipolar these days, is going to be a strong predisposition for psychotic episodes, made much greater anytime one takes a sympathomimetic drug such as amphetamine, but also methylphenidate, Ritalin, is going to increase that likelihood of psychotic episodes.

因此，如果第一个亲戚患有精神分裂症或双相抑郁症，或者有时被称为双相情感障碍，有时也被称为双相情感障碍，那么，这将是精神病发作的强烈倾向，每当服用拟交感神经药物（如安非他明）以及哌醋甲酯、利他林时，这种倾向就会增加，这会增加精神病发作的可能性。

Then comes the question of, if somebody has a psychotic episode as the consequence of taking any of these drugs, whether or not it's been prescribed for ADHD or not, will those psychotic symptoms go away after the person stops taking the drug?

接下来的问题是，如果某人因服用任何这些药物而出现精神病发作，无论该药物是否用于治疗多动症，在该人停止服用药物后，这些精神病症状会消失吗？

There appears to be a divide in the literature, or rather a divide according to drug, such that people that take Ritalin, methylphenidate, and have a psychotic episode, often, not always, but most often, if they stop taking methylphenidate, the psychotic episode will cease.

文献中似乎存在分歧，或者更确切地说，根据药物存在分歧，例如，服用利他林、哌醋甲酯的人经常（并非总是）出现精神病发作，但最常见的是，如果他们停止服用哌醋甲酯，精神病发作就会停止。

It's not always the case, but most often times it will cease.

情况并非总是如此，但大多数时候它会停止。

Whereas in individuals who have a predisposition to psychosis, or even if they're not aware of a predisposition to psychosis and they take Adderall, which as you recall is a combination of D and L-amphetamine, they can have psychotic episodes that sometimes are very long-lasting, even after the cessation of the drug.

然而，对于有精神病倾向的人，或者即使他们不知道有精神病倾向并且服用阿得拉（你记得是 D 和 L-安非他明的组合），他们可能会出现精神病发作，有时甚至在停药后也会持续很长时间。

And while that might sound kind of shocking and really scary, and indeed it is scary, it perhaps shouldn't shock us that much because if you recall D-amphetamine, which there's a lot of in Adderall, it's a very potent way of increasing dopamine, and anytime you potently increase dopamine in a person who has a predisposition to psychotic episodes, you are shifting the whole system toward a greater propensity for psychosis.

虽然这可能听起来有点令人震惊和可怕，而且确实很可怕，但它也许不应该让我们感到那么震惊，因为如果你回想起阿得拉中含有大量的D-安非他明，它是增加多巴胺的一种非常有效的方法，每当你有效地增加一个有精神病发作倾向的人的多巴胺时，你正在将整个系统转向更容易患精神病的倾向。

This would also be the appropriate time to talk about meth, methamphetamine.

这也是谈论冰毒、冰毒的合适时机。

Again, methamphetamine is considered an illicit drug, a drug of abuse.

同样，甲基苯丙胺被认为是一种非法药物，一种滥用药物。

It is responsible for a lot of the misfortune and tragedy that you see on the streets of major cities and even outside of major cities in rural areas.

在大城市的街道上，甚至在大城市以外的农村地区，你所看到的许多不幸和悲剧都是它造成的。

It has all sorts of negative effects on health, including oral health, cardiovascular health.

它对健康有各种负面影响，包括口腔健康、心血管健康。

It is neurotoxic to serotonergic neurons, so it kills serotonin neurons.

它对血清素能神经元具有神经毒性，因此会杀死血清素神经元。

That is absolutely clear.

这是绝对清楚的。

It kills dopaminergic neurons.

它杀死多巴胺能神经元。

That is absolutely clear.

这是绝对清楚的。

One of the ways that methamphetamine creates so many of the problems that it does, meaning effects on the body, abuse potential, addictive potential, the fact that methamphetamine can spark psychosis in those that have a predisposition to psychosis, but also that it can create psychosis in individuals who have no predisposition to psychosis.

甲基苯丙胺造成如此多问题的方式之一，即对身体的影响、滥用潜力、成瘾潜力，事实上，甲基苯丙胺可以在那些有精神病倾向的人中引发精神病，但它也可以在没有精神病倾向的人中产生精神病。

Right, all of this points to methamphetamine just being a terrible drug all around, and yet, if you recall back to the beginning of the episode, there is one form of prescription methamphetamine, but its uses are extremely narrow, and it's probably best left out of this conversation because its uses are so narrow in the clinical sense.

是的，所有这些都表明甲基苯丙胺是一种可怕的药物，然而，如果你回想起这一集的开头，有一种形式的处方甲基苯丙胺，但它的用途非常狭窄，并且最好将其排除在这次讨论之外，因为它的用途在临床意义上非常狭窄。

I managed to talk to one expert.

我设法与一位专家交谈。

This is a board-certified psychiatrist who's expert in ADHD, who is also very familiar with the psychosis symptoms induced by methamphetamine and by various ADHD drugs in people who have the predisposition.

这是一位经过委员会认证的精神科医生，是多动症方面的专家，他也非常熟悉甲基苯丙胺和各种多动症药物对有易动症倾向的人引起的精神病症状。

They made it very clear that any of the sympathomimetic ADHD drugs that are of the amphetamine variety, so that would be Adderall and extended release Adderall, that would be pure Dexedrine, or any variants that include amphetamine are going to have higher likelihood of inducing psychosis in people that have a predisposition to psychosis.

他们非常明确地表示，任何属于安非他明品种的拟交感神经多动症药物，即阿德拉和缓释阿德拉，即纯右旋糖苷，或任何包含安非他明的变体，都更有可能在有精神病倾向的人中诱发精神病。

And yet they did assure me that at appropriately prescribed and safe dosages, that the total incidence of psychosis in people that take those drugs is still fairly low and not that much greater than in the general population.

然而他们确实向我保证，在适当的处方和安全剂量下，服用这些药物的人的精神病总发病率仍然相当低，并不比一般人群高很多。

Although there is an increased risk, it's not that severe.

虽然风险有所增加，但并没有那么严重。

And they also highlighted the fact that methylphenidate, Ritalin, carries a lower potential for inducing psychosis.

他们还强调了哌醋甲酯、利他林诱发精神病的可能性较低的事实。

Not zero, but a lower level of inducing psychosis than for the amphetamine-type sympathomimetics.

不是零，而是比安非他明类交感神经药诱发精神病的水平更低。

Now, one exception is Vyvanse, that long-release D-amphetamine that we talked about earlier.

现在，一个例外是 Vyvanse，我们之前讨论过的一种长释 D-安非他明。

There does seem to be something protective about that long-duration release of D-amphetamine that occurs with Vyvanse, which is not to say that there's zero abuse or addictive potential with Vyvanse.

Vyvanse 发生的 D-安非他明的长期释放似乎确实具有某种保护作用，这并不是说 Vyvanse 的滥用或成瘾潜力为零。

I was told by the same individual that indeed, they've had knowledge of patients trying to increase the rate of absorption of Vyvanse and release of Vyvanse, or technically of the D-amphetamine, in order to get more of a high from Vyvanse as opposed to just the extended release.

同一个人告诉我，事实上，他们知道患者试图提高 Vyvanse 的吸收率和 Vyvanse 的释放率，或者从技术上讲是 D-安非他明，以便从 Vyvanse 中获得更多的快感，而不仅仅是延长释放。

But they did assure me, however, that Vyvanse seems to be associated with fewer psychotic episodes and less abuse and addictive potential overall.

但他们确实向我保证，Vyvanse 似乎与较少的精神病发作、较少的滥用和成瘾潜力有关。

Which, again, is not to say that it's a perfectly safe drug, but really this just highlights the fact that the kinetics or the time course of dopamine and norepinephrine release that's caused by a given drug is going to correlate very strongly with its abuse potential and addictive potential and its potential to induce psychotic episodes.

再说一次，这并不是说它是一种完全安全的药物，但这实际上只是强调了一个事实，即由给定药物引起的多巴胺和去甲肾上腺素释放的动力学或时间过程将与其滥用潜力、成瘾潜力以及诱发精神病发作的潜力密切相关。

And this is where the discussion about meth becomes especially relevant.

这就是关于冰毒的讨论变得特别重要的地方。

One of the reasons why meth is so dangerous in terms of its addictive potential and its potential to induce psychotic episodes is, first of all, how much dopamine it releases, again, five times more than any of the other drugs that we've been talking about, but also how fast that peak comes on.

就其成瘾潜力和诱发精神病发作的潜力而言，冰毒如此危险的原因之一是，首先，它释放的多巴胺量比我们一直在谈论的任何其他药物都要多五倍，而且多巴胺高峰出现的速度有多快。

It's a very fast onset, and that's true whether or not people are snorting it, whether or not they're taking it orally, or especially if they inject it intravenously.

它起效非常快，无论人们是否通过鼻吸、口服或静脉注射，情况都是如此。

But meth, because it increases dopamine so fast and to such a great degree, and then the peak in dopamine comes down very fast as well, and it drops below the baseline levels of dopamine that were present initially.

但是冰毒，因为它增加多巴胺的速度如此之快，程度如此之大，然后多巴胺的峰值也很快下降，并且下降到最初存在的多巴胺基线水平以下。

That's one of the reasons why methamphetamine is so dangerous in terms of addiction and in terms of psychotic episodes.

这就是甲基苯丙胺在成瘾和精神病发作方面如此危险的原因之一。

This gets back to a bunch of issues we've talked about before on the Huberman Lab podcast about dopamine kinetics, and I've done two episodes on dopamine that I'll refer you to.

这又回到了我们之前在 Huberman 实验室播客上讨论过的关于多巴胺动力学的一系列问题，我已经做了两集关于多巴胺的节目，我将向您推荐。

One is called Dopamine, Motivation, and Drive, which is all about dopamine and regulating dopamine, and the other one is about optimizing dopamine.

一个叫做“多巴胺、动机和驱动力”，都是关于多巴胺和调节多巴胺的，另一个是关于优化多巴胺的。

It's more of a toolkit-focused episode.

这更像是一个以工具包为中心的剧集。

Both those you can find at hubermanlab.com.

您可以在 hubermanlab.com 上找到这两个内容。

But the general takeaway that's relevant for what we're talking about now is that with dopamine, it's not just about the absolute levels of dopamine that are reached, but how long-lasting those increases in dopamine are.

但与我们现在讨论的内容相关的一般要点是，对于多巴胺，这不仅仅是达到的多巴胺的绝对水平，而是多巴胺增加的持续时间。

So with Vyvanse, even though Vyvanse is D-amphetamine, it's fairly potent, not as potent as meth, but fairly potent at increasing dopamine and norepinephrine.

因此，对于 Vyvanse，尽管 Vyvanse 是 D-安非他明，但它的效力相当强，不如冰毒那么强，但在增加多巴胺和去甲肾上腺素方面相当有效。

It's a long extended release in dopamine and norepinephrine, which reduces its overall abuse potential because it doesn't tend to create that immediate euphoria and high and then crash below baseline.

它是多巴胺和去甲肾上腺素的长期缓释，这降低了其整体滥用潜力，因为它不会立即产生欣快感和高度，然后跌至基​​线以下。

A lot of you will hear that it increases dopamine a lot and then stays up as translating to, okay, well then you're just euphoric for 16 hours.

很多人都会听说它会大量增加多巴胺，然后熬夜，意思是，好吧，那么你就会欣快地度过 16 个小时。

But that's not the case.

但事实并非如此。

When it comes to dopamine, it's an issue of how high that peak is and whether or not that peak is stable, or whether or not it comes down again.

当谈到多巴胺时，问题在于峰值有多高，峰值是否稳定，或者是否会再次下降。

And when it comes to psychotic episodes or addictive potential, it seems that any drug or behavior that increases dopamine very quickly and then brings dopamine down very quickly is what sets the high potential for addiction and abuse and for inducing psychotic episodes.

当谈到精神病发作或成瘾潜力时，似乎任何快速增加多巴胺然后又迅速降低多巴胺的药物或行为都极有可能导致成瘾和滥用以及诱发精神病发作。

So that's why I'm talking about these two things in parallel.

这就是为什么我同时讨论这两件事。

And now it should be very clear why Vyvanse doesn't have so much addictive and abuse potential and has at least lower potential for inducing psychotic episodes.

现在应该很清楚为什么 Vyvanse 没有那么大的成瘾和滥用潜力，并且至少诱发精神病发作的可能性较低。

And it should also be clear to you that for people who do not have ADHD as a child, or for people that do not have ADHD in adulthood, if they were to take any, truly any of the compounds that we're talking about thus far, methylphenidate, Ritalin, Adderall, Vyvanse, Dexedrine, and certainly methamphetamine, what we observe from neuroimaging studies is that these people get enormous increases in dopamine.

你还应该清楚，对于儿童时期没有多动症的人，或者成年后没有多动症的人来说，如果他们服用我们迄今为止讨论的任何一种化合物，哌醋甲酯、利他林、阿得拉、Vyvanse、右旋糖胺，当然还有甲基苯丙胺，我们从神经影像学研究中观察到，这些人的多巴胺会大幅增加。

They're not familiar with these drugs, so the increases in dopamine are just cosmic for them.

他们对这些药物并不熟悉，所以多巴胺的增加对他们来说简直是天大的事。

They experience a lot of euphoria.

他们体验到很多欣快感。

Even if the dosages are low, the euphoria is associated with a very heightened degree of focus they've never really felt before.

即使剂量很低，欣快感也会带来他们以前从未真正感受到的高度专注。

Here, what I'm talking about is a lot of the recreational and off-prescription use of Adderall and things like it.

在这里，我所说的是阿得拉和类似药物的许多娱乐性和非处方用途。

And what we know is that that sets in motion both a potential for abuse and addiction to that feeling and substance, as well as a higher potential for psychotic episodes down the road.

我们所知道的是，这会引发对这种感觉和物质的滥用和成瘾，以及未来更高的精神病发作可能性。

Okay, so put differently, children who have ADHD and are prescribed any of these drugs, or adults who have ADHD and are prescribed any of these drugs, who take them for some period of time, are actually at lesser risk to all of the issues related to having chronically elevated and greatly elevated dopamine as a kind of first-time event or as a rare event.

好吧，换句话来说，患有注意力缺陷多动症并服用任何这些药物的儿童，或者患有注意力缺陷多动症并服用任何这些药物的成年人，服用一段时间后，实际上患与长期升高和大幅升高的多巴胺作为一种首次事件或罕见事件相关的所有问题的风险较小。

Whereas anyone who takes these drugs without a prescription and decides, okay, I want to focus more, or I'm going to use this to stay up for a couple of days, in other words, using it recreationally or using it for, quote-unquote, performance enhancement, is at far greater risk for addiction to these substances because of the amplitude and the time course of dopamine that results when one takes these drugs just out of the blue.

然而，如果任何人在没有处方的情况下服用这些药物并决定，好吧，我想更加集中注意力，或者我要用它来熬夜几天，换句话说，使用它来娱乐或使用它来提高性能，那么对这些物质上瘾的风险要大得多，因为当一个人突然服用这些药物时，会产生多巴胺的幅度和时间过程。

And so, for that reason, I really want to caution everybody against using any of the compounds that I've discussed thus far unless it's been prescribed to you by a physician for the specific purpose of ADHD.

因此，出于这个原因，我真的想提醒大家不要使用我迄今为止讨论过的任何化合物，除非医生为您开了用于治疗多动症的特定药物。

Now, I'm sure someone out there is screaming from the back, "Wait, if a kid takes these drugs because they're prescribed them for ADHD, the very first time they take them, they're going to have a huge amplitude dopamine response."

现在，我确信有人在后面尖叫，“等等，如果一个孩子因为治疗多动症而服用这些药物，那么他们第一次服用这些药物时，他们将会产生大幅的多巴胺反应。”

Or if an adult goes in and talks to their psychiatrist and says, "I'm having issues with focusing," and they're prescribed one of these meds for ADHD, and they take it, they're going to have a huge amplitude dopamine response.

或者，如果一个成年人进去与他们的精神科医生交谈并说：“我的注意力有问题”，然后他们被开了其中一种治疗多动症的药物，并且他们服用了它，他们将会产生大幅的多巴胺反应。

Isn't that going to set in motion all the same things that somebody who is using these drugs recreationally would have?

难道这不会引发与那些消遣性使用这些药物的人会发生的同样的事情吗？

And indeed, that's one of the reasons why a lot of psychiatrists will start with a very low dosage, or the lowest possible dosage, to see how somebody responds to that low dosage, and then over time might or might not increase that dosage.

事实上，这就是为什么许多精神科医生会从非常低的剂量或尽可能低的剂量开始，看看某人对低剂量的反应如何，然后随着时间的推移可能会或可能不会增加该剂量的原因之一。

In fact, they might even bring it down further, depending on how sensitive somebody is to the drug.

事实上，他们甚至可能进一步降低，这取决于某人对药物的敏感程度。

But equally important is the fact that it is the repeated taking of that drug by the child with ADHD or by the adult with ADHD that actually leads to lesser and lesser peaks in dopamine each time.

但同样重要的是，患有多动症的儿童或患有多动症的成人重复服用该药物实际上导致每次多巴胺的峰值越来越小。

Which is not to say that the person becomes entirely desensitized to the effects of the drug, but rather that the system equilibrates through what's called homeostatic plasticity.

这并不是说人对药物的作用完全不敏感，而是说系统通过所谓的稳态可塑性达到平衡。

It's sometimes referred to broadly as habituation to a drug.

有时它被广泛地称为对药物的习惯。

But there are systems in the brain and body that regulate the connections between neurons so that if dopamine and norepinephrine are elevated above baseline levels for a while, the system normalizes so that instead, the connections between neurons become stronger, and there isn't the critical requirement for all that increase in dopamine and norepinephrine.

但大脑和身体中有一些系统可以调节神经元之间的连接，因此，如果多巴胺和去甲肾上腺素在一段时间内升高到基线水平以上，系统就会恢复正常，从而神经元之间的连接变得更强，并且不需要多巴胺和去甲肾上腺素的增加。

I realize that might sound a little bit technical, but basically what I'm saying is the response that somebody has to taking a drug for the first time is far and away different than the response to a drug that somebody has if they are taking the same drug day after day after day.

我意识到这听起来可能有点技术性，但基本上我想说的是，某人第一次服用药物的反应与日复一日服用同一种药物的人对药物的反应截然不同。

This gets to another issue, which is not discussed that often these days, but that is really important.

这就涉及到另一个问题，虽然现在不经常讨论这个问题，但这确实很重要。

If you go back to the original clinical literature on the sympathomimetics, what you'll find is that the original use of these sympathomimetics to treat childhood ADHD suggested that children not take these drugs every single day.

如果您回顾有关拟交感神经药的原始临床文献，您会发现这些拟交感神经药最初用于治疗儿童多动症时建议儿童不要每天服用这些药物。

Now, I'm not recommending that kids take drug holidays because I'm not a clinician.

现在，我不建议孩子们休药物假期，因为我不是临床医生。

I'm not promoting any specific dose or dosing regimen.

我不提倡任何特定剂量或给药方案。

But in speaking, again, to a psychiatrist expert in ADHD, who by the way, is going to be a guest on this podcast in the not-too-distant future, what he told me was that many of these drugs were designed to be taken during the school week for children with weekends off, or during the school year with weekends off, but then also with vacations during the summer holidays.

但在与一位多动症精神病学专家交谈时，顺便说一下，他将在不久的将来成为这个播客的嘉宾，他告诉我，这些药物中有许多是设计为在周末休息的孩子在学周期间服用的，或者是在周末休息的学年期间服用的，但也可以在暑假期间服用。

And that these days, rarely, if ever, is that the pattern of intake that these kids are following.

如今，这些孩子很少遵循这种摄入模式。

And why that is has interesting sociological and financial explanations.

其原因有有趣的社会学和金融解释。

I'm not alluding to any kind of conspiracy here, but this is an aspect of the dosing with these drugs that has sort of fallen away in recent years.

我在这里并不是指任何形式的阴谋，但这是近年来这些药物剂量的一个方面，已经逐渐消失。

But I think is really interesting, and it's something that actually was supported for the treatment of adult ADHD as well.

但我认为这真的很有趣，而且它实际上也被支持用于治疗成人多动症。

Again, there is a very Different biological and neuroplastic response to taking a drug once versus taking a drug for, say, five days and then taking weekends off, to taking a drug over and over again every single day for a pattern of years.

同样，服用一次药物与服用药物（例如服用五天，然后周末休息），与连续几年每天重复服用药物相比，存在非常不同的生物和神经塑性反应。

And when exploring the literature in preparation for this episode, I confess it was a bit dizzying to find answers to what are the long-term effects of taking Adderall, or what are the long-term effects of taking Vyvanse, et cetera.

在为这一集做准备时探索文献时，我承认，寻找服用 Adderall 的长期影响是什么，或者服用 Vyvanse 的长期影响是什么等问题的答案有点令人眼花缭乱。

In fact, most of the literature on the long-term effects of taking drugs to treat ADHD has focused on methylphenidate, on Ritalin.

事实上，大多数关于服用药物治疗多动症的长期影响的文献都集中在哌醋甲酯和利他林上。

There are studies on Vyvanse and Adderall, and actually, those were the studies that I will link in the show note captions primarily, because that's where most of the interest is these days.

有一些关于 Vyvanse 和 Adderall 的研究，实际上，我将主要在节目注释标题中链接这些研究，因为这是目前最受关注的地方。

The reason why so many of the studies have focused on methylphenidate, on Ritalin, is largely because that was one of the first drugs used to treat ADHD.

如此多的研究之所以集中在哌醋甲酯、利他林上，很大程度上是因为它是最早用于治疗多动症的药物之一。

So in terms of addressing long-term effects of kids treated with ADHD meds, those kids are now adults, and therefore can be neuroimaged and assessed, whereas a lot of kids that have been prescribed Adderall or Vyvanse or similar have not yet made it to stages of life in which we can answer that question directly.

因此，就解决接受 ADHD 药物治疗的儿童的长期影响而言，这些孩子现在已经是成年人，因此可以进行神​​经影像和评估，而许多服用 Adderall 或 Vyvanse 或类似药物的孩子尚未达到我们可以直接回答这个问题的人生阶段。

There are a few studies, and I've made it clear to include those studies in my description of results today.

有一些研究，我已经明确表示将这些研究纳入我今天的结果描述中。

In particular, the result I talked about earlier, where there's an improvement in executive function in kids that have taken ADHD meds or adults that have taken ADHD meds for a longer period of time, anywhere from months to years.

特别是我之前提到的结果，服用多动症药物的儿童或长期服用多动症药物的成年人（从几个月到几年）的执行功能有所改善。

Those studies did include both Adderall and Vyvanse and methylphenidate, and again, I'll link to those studies.

这些研究确实包括了 Adderall、Vyvanse 和哌醋甲酯，我将再次链接到这些研究。

But by and large, most of what we know about the long-term effects of any of these drugs has to do primarily with studies of methylphenidate.

但总的来说，我们对这些药物的长期影响的大部分了解主要与哌醋甲酯的研究有关。

I'd like to spend a little bit of time talking about some compounds that are not considered amphetamines at all, but that are now being used to treat ADHD, both in children and adults more frequently.

我想花一点时间讨论一些根本不被视为安非他明的化合物，但它们现在更频繁地用于治疗儿童和成人的多动症。

The major drug in this category of non-amphetamine treatments for ADHD is modafinil, which is also called by its commercial name, Provigil.

此类非安非他明治疗多动症的主要药物是莫达非尼，其商业名称也称为 Provigil。

There's a variant on this, which is armodafinil, which goes by the brand name Nuvigil.

它有一个变体，即阿莫达非尼（armodafinil），其品牌名称为 Nuvigil。

The major difference between modafinil and armodafinil, aside from having a slight chemical difference, is that modafinil was released first.

莫达非尼和阿莫达非尼之间的主要区别除了轻微的化学差异外，还在于莫达非尼首先被释放。

Armodafinil is the second in the generation of these drugs.

阿莫达非尼是这些药物中的第二个。

And modafinil tends to be very expensive.

而且莫达非尼往往非常昂贵。

That's one of the reasons why it's prohibitive for some people to take.

这就是为什么有些人禁止服用的原因之一。

It can be as expensive as $25 a pill or more, so more than $1,000 per month.

它的价格可能高达每片 25 美元或更多，因此每月超过 1,000 美元。

And armodafinil tends to be far, far less expensive.

而且阿莫达非尼往往要便宜得多。

I've talked to a couple experts about whether or not there are any genuine differences between these two drugs, and they report no, although consumers of these drugs, for whatever reason, whether or not it's placebo or not, report yes, there is a difference.

我曾与几位专家讨论过这两种药物之间是否存在任何真正的差异，他们报告没有，尽管这些药物的消费者，无论出于何种原因，无论是否是安慰剂，报告是的，存在差异。

When I say placebo, I in no way mean that these drugs are just acting as placebo.

当我说安慰剂时，我绝不是说这些药物只是充当安慰剂。

I just mean that people tend to get very attached to certain drugs and whether or not the brand name or the generic version works better for them.

我只是说，人们往往对某些药物非常执着，无论品牌药还是仿制药对他们来说效果更好。

There's all sorts of lore about this.

关于这一点有各种各样的传说。

In fact, there are a lot of people out there who strongly feel that brand name Adderall works better than generic Adderall for them.

事实上，有很多人强烈认为品牌阿得拉比普通阿得拉更适合他们。

There are a lot of people out there who say the same thing about Vyvanse.

有很多人对 Vyvanse 也有同样的看法。

There are a lot of people out there who say the same thing about Ritalin and all sorts of drugs.

有很多人对利他林和各种药物都持同样的看法。

Whether or not that's true or not is unclear.

这是否属实尚不清楚。

It is clear that generic versions of drugs can use binders and other things that are in the pill or capsule that are different than what the brand name pill or capsule uses as binders to hold the drug together, and that can impact rates of release and metabolism, et cetera.

显然，仿制药可以使用药丸或胶囊中的粘合剂和其他物质，这些物质与品牌药丸或胶囊用作粘合剂将药物固定在一起的物质不同，这可能会影响释放和代谢速率等。

But a lot of this is just lore.

但其中很多只是传说。

In fact, I went into the literature to try and find any real concrete support for the idea that generic Adderall is less potent or less effective than brand name Adderall.

事实上，我查阅了文献，试图找到任何真正具体的证据来支持这一观点，即仿制药阿得拉的效力或效果不如品牌阿得拉。

And despite the tens of thousands of people who will say to the contrary, I could not find any peer-reviewed published data about that.

尽管有成千上万的人会提出相反的观点，但我找不到任何经过同行评审的已发布数据。

So who knows?

那么谁知道呢？

Maybe it's a belief effect, as it's called.

也许这就是所谓的“信念效应”。

Maybe there's a real difference there.

也许那里确实存在差异。

Nowadays, modafinil and armodafinil are prescribed for a huge range of daytime sleepiness issues.

如今，莫达非尼和阿莫达非尼被用于治疗多种白天嗜睡问题。

We're talking about narcolepsy, but there are also people who suffer from daytime sleepiness related to dementia, daytime sleepiness related to post-surgery anesthesia.

我们谈论的是发作性睡病，但也有人患有与痴呆症相关的白天嗜睡、与手术后麻醉相关的白天嗜睡。

So there's this thing where people have surgery, and then they come out of surgery, and they feel better for a few days, but then they find that they aren't recovering their normal levels of wakefulness.

因此，人们在接受手术后，在手术结束后几天感觉好一些，但随后他们发现自己没有恢复正常的清醒水平。

So it's prescribed sometimes to try and get people back into a normal state of wakefulness.

因此，有时会尝试让人们恢复正常的清醒状态。

It's been prescribed for traumatic head injury, after stroke.

它被用于治疗中风后的头部外伤。

Again, all of these prescribed uses have to be carried out by a certified physician.

同样，所有这些规定的用途都必须由经过认证的医生进行。

You really don't want to start cowboying the use of modafinil or armodafinil or any other prescription drug for that matter.

您真的不想开始使用莫达非尼或阿莫达非尼或任何其他处方药。

I must say that in discussing all these different drugs during today's episode, I have zero knowledge of any of these drugs from a firsthand experience, except for armodafinil.

我必须说，在今天的节目中讨论所有这些不同的药物时，除了阿莫达非尼之外，我对这些药物的第一手经验了解为零。

Back in 2017, I was prescribed a very, very low dose of armodafinil for jet lag, for daytime sleepiness issues, really, when I was traveling overseas to give a talk.

早在 2017 年，当我去海外演讲时，医生给我开了非常非常低剂量的阿莫达非尼，以缓解时差反应和白天嗜睡问题。

So armodafinil was given to me in a 25 milligram tablet It was advised to me that I take a half or even a quarter of that, so I started with a quarter.

所以我给了我 25 毫克的阿莫达非尼片剂。有人建议我服用一半甚至四分之一，所以我开始服用四分之一。

I am a believer in minimal effective dose.

我坚信最小有效剂量。

I'm also somebody who's fairly hypersensitive to most medication, so I took what I measured out to be five to seven milligrams of armodafinil, and what I experienced was pretty profound.

我也是一个对大多数药物都相当过敏的人，所以我测量了五到七毫克的阿莫达非尼，我的经历非常深刻。

Certainly, it relieved any daytime sleepiness.

当然，它缓解了白天的困倦。

In fact, it made me feel extremely alert for a period of about four to six hours.

事实上，它让我在大约四到六个小时的时间内感到极度警觉。

I can't say it was the most comfortable state, although I did not feel as if I had a racing heart or anything of that sort.

我不能说这是最舒服的状态，尽管我并不觉得自己有心跳加速或类似的感觉。

I basically felt as if I was in a narrow tunnel of attention for that entire period.

在那整个时期，我基本上感觉自己好像处于一个狭窄的注意力隧道中。

One thing I did not like about the experience is that it was a very hard experience to come down from.

我不喜欢这次经历的一件事是，这是一次非常艰难的经历。

There was no crash, but I found that that high arousal state didn't taper off for many hours later.

没有发生崩溃，但我发现这种高度兴奋状态在几个小时后并没有逐渐减弱。

Even though it was most heightened for four hours, I would say anywhere from eight to 12 hours later, I still felt like I was blinking once every four minutes or so.

尽管它在四个小时内达到最高，我想说的是八到十二小时后，我仍然感觉自己每四分钟左右眨眼一次。

And I've certainly been accused on this podcast and at other times of blinking too seldom.

在这个播客和其他时候，我肯定被指责眨眼太少。

To my knowledge, I don't have ADHD.

据我所知，我没有多动症。

I've never been prescribed ADHD meds.

我从未被开过治疗多动症的药物。

I've never been tested for ADHD.

我从未接受过多动症测试。

I don't think I have ADHD, and yet taking armodafinil certainly increased my levels of attention, but at least by that one experience, it's not something that I would want to repeat again.

我不认为我患有注意力缺陷多动症，但服用阿莫达非尼确实提高了我的注意力水平，但至少通过那一次经历，我不想再次重复这件事。

I certainly would not want to be in that state for learning new material.

我当然不想处于那种学习新材料的状态。

When I sit down to research a podcast or research papers in my lab or forage for information or learn from people or books or lectures or podcasts, I want to be in a state of alertness but calm, where I can really consider the ideas, where I can script things out by hand.

当我坐下来在实验室里研究播客或研究论文，或者寻找信息，或者向人、书籍、讲座或播客学习时，我希望处于一种警觉但冷静的状态，这样我可以真正考虑想法，可以手动编写脚本。

I'm a big believer in writing things out by hand to remember them later, drawing little diagrams.

我非常相信用手写下来以便以后记住它们，画一些小图表。

I would not want to be in the state that even that very low dose of armodafinil put me in, in order to learn.

我不想为了学习而处于这样的状态，即使是非常低剂量的阿莫达非尼也让我陷入这样的状态。

And I should mention that both modafinil and armodafinil are associated with a good number of side effects if they don't agree with you or if the dosage is too high, things like decreased appetite.

我应该提到的是，如果莫达非尼和阿莫达非尼与您的观点不一致或者剂量太高，例如食欲下降，它们都会产生很多副作用。

People can get a runny nose, headache.

人们可能会流鼻涕、头痛。

There's this instance of skin rashes.

有一个皮疹的例子。

In fact, one of the reasons why modafinil and armodafinil aren't more broadly prescribed is that there's a very rare skin condition in which people who have taken certain drugs, not just modafinil or armodafinil, have developed these very severe burn type blisters, and in some cases, this can be fatal.

事实上，莫达非尼和阿莫达非尼没有得到更广泛处方的原因之一是，有一种非常罕见的皮肤病，服用某些药物（而不仅仅是莫达非尼或阿莫达非尼）的人会出现这些非常严重的烧伤型水泡，在某些情况下，这可能是致命的。

This is, again, very rare, and it was observed in at least one patient who took modafinil as part of a trial for modafinil as a treatment for ADHD.

这种情况再次非常罕见，至少在一名服用莫达非尼作为莫达非尼治疗多动症试验的一部分的患者中观察到了这种情况。

It's called Stevens-Johnson syndrome.

这被称为史蒂文斯-约翰逊综合症。

Please, if you are squeamish to images of skin abrasions and lesions and things of that sort, please don't look it up on the internet unless you're able to handle that, and maybe not at all.

拜托，如果您对皮肤擦伤、损伤和类似事物的图像感到反感​​，请不要在互联网上查找，除非您能够处理，也许根本无法处理。

But the point here is that one of the reasons that modafinil and armodafinil are not more widely prescribed for ADHD and that it's still only prescribed off-label, is that Stevens-Johnson syndrome was flagged as kind of a potential risk.

但这里的要点是，莫达非尼和阿莫达非尼没有更广泛地用于治疗多动症，而且仍然只是在标签外使用，原因之一是史蒂文斯-约翰逊综合征被标记为一种潜在风险。

Although the ADHD specialists that I spoke to are somewhat frustrated with that because they insist that the frequency of this syndrome that causes this skin rash that's sometimes fatal is no more frequent in those that took modafinil in this trial than with other drugs that have been approved.

尽管我采访过的多动症专家对此有些沮丧，因为他们坚持认为，在本次试验中服用莫达非尼的患者中，这种导致有时致命的皮疹的综合征的发生频率并不比使用其他已批准药物的患者更频繁。

So this gets into all sorts of issues around what drugs make it to approval and which ones don't.

因此，这涉及到哪些药物能够获得批准、哪些药物不能获得批准的各种问题。

And as we know, modafinil and armodafinil are already being prescribed in the general population for other things.

据我们所知，莫达非尼和阿莫达非尼已经在普通人群中用于其他用途。

This was dealing specifically with the question of whether or not it should be prescribed in kids with ADHD.

这是专门处理是否应该给患有多动症的孩子开处方的问题。

And certainly, I am a proponent of exerting extreme caution when thinking about which drugs should be approved for the treatment of anybody, but especially kids.

当然，我支持在考虑哪些药物应该被批准用于治疗任何人（尤其是儿童）时要格外谨慎。

And to round out our discussion of drugs used for the treatment of ADHD that fall into, let's call it the atypical category.

为了完善我们对用于治疗多动症的药物的讨论，我们将其称为非典型类别。

The typical category being Adderall, Vyvanse, methylphenidate, and things of that variety.

典型的类别是 Adderall、Vyvanse、哌醋甲酯以及此类物质。

The less typical would be modafinil, armodafinil, provigil, Wellbutrin, and so forth.

不太典型的是莫达非尼、阿莫达非尼、普罗维吉尔、维布特林等。

The last in this category of atypical is guanfacine.

此类非典型药物中的最后一个是胍法辛。

Guanfacine is an interesting compound.

胍法辛是一种有趣的化合物。

It's a compound that was developed to lower blood pressure, and indeed it does lower blood pressure, and it is an alpha-2a agonist, alpha-2a being a receptor for norepinephrine.

它是一种为降低血压而开发的化合物，确实可以降低血压，它是一种 α-2a 激动剂，α-2a 是去甲肾上腺素的受体。

So guanfacine is a non-stimulant medication to treat ADHD, and it's also used to treat some other conditions as well, that is only working on the noradrenergic system and is not tapping into the dopamine system.

因此，胍法辛是一种治疗多动症的非刺激性药物，它也可用于治疗其他一些疾病，它仅对去甲肾上腺素能系统起作用，而不能利用多巴胺系统。

But all the other stuff that we talked about is really ramping up dopamine and norepinephrine.

但我们谈论的所有其他东西确实会增加多巴胺和去甲肾上腺素。

Guanfacine is only increasing norepinephrine, and it's doing so by what we say agonizing or stimulating one particular aspect of the noradrenergic system, and that's the alpha-2a system.

胍法辛只是增加去甲肾上腺素，它是通过我们所说的痛苦或刺激去甲肾上腺素能系统的某一特定方面（即 α-2a 系统）来达到这一目的。

What's interesting about guanfacine is that it has a bunch of pathways that it activates that feed back onto the autonomic nervous system to dampen down the activation of the sympathetic nervous system.

胍法辛的有趣之处在于，它激活了一系列通路，这些通路反馈到自主神经系统，以抑制交感神经系统的激活。

So whereas most of what we talked about today are sympathomimetics, they tend to make us more ramped up, more aroused and alert, guanfacine is doing the opposite.

因此，尽管我们今天讨论的大部分内容都是拟交感神经药，它们往往会让我们更加兴奋、更加兴奋和警觉，而胍法辛则恰恰相反。

And as a consequence, it's not prescribed that often because a lot of times when people take guanfacine, it either has no effect on ADHD symptoms, or it tends to make people feel very sleepy.

因此，人们并不经常服用胍法辛，因为很多时候，人们服用胍法辛时，它要么对多动症症状没有影响，要么会让人们感到非常困倦。

However, there's a small subset of individuals, probably about five to 10% of people that try it, including kids, that do get some significant relief from their ADHD symptoms, and they seem to tolerate guanfacine better than they're tolerating some of the other drugs that we've talked about up until now.

然而，有一小部分人，可能是大约 5% 到 10% 的尝试过的人，包括儿童，他们的多动症症状确实得到了一些显着缓解，而且他们对胍法辛的耐受性似乎比对我们迄今为止讨论过的其他一些药物的耐受性更好。

The way guanfacine works is also really interesting.

胍法辛的作用方式也很有趣。

You're now familiar with the locus coeruleus, this packet, or we call it a nucleus of neurons in the back of the brain that release norepinephrine at other sites in the brain, and they're going to be those alpha-2a receptors that guanfacine works on and stimulates lots of different places in the brain related to increasing salience and relevance of particular stimuli that we see and that we need to attend to.

你现在已经熟悉了蓝斑，这个包，或者我们称之为大脑后部的神经元核，它们在大脑的其他部位释放去甲肾上腺素，它们将是胍法辛起作用并刺激大脑中许多不同部位的α-2a受体，这些部位与增加我们看到的和需要注意的特定刺激的显着性和相关性有关。

It appears that guanfacine can activate the prefrontal cortical networks in ways that are above their normal baseline, so that's good.

看来胍法辛可以以高于正常基线的方式激活前额皮质网络，所以这很好。

So improvements in executive function, that orchestra or teacher-like function we talked about before, and can increase the efficacy of that output from locus coeruleus.

因此，执行功能的改善，即我们之前讨论过的管弦乐队或教师般的功能，可以提高蓝斑输出的效率。

And what that seems to do is increase the coordinated firing of locus coeruleus neurons with prefrontal cortex.

这似乎是增加了蓝斑神经元与前额皮质的协调放电。

So in many ways, it's acting like a fine-tuning of that orchestra conductor operation that is so valuable in teaching these brain circuits during childhood of how to attend to one thing and ignore everything else.

因此，从很多方面来说，它就像是对管弦乐队指挥操作的微调，这对于在童年时期教导这些大脑回路如何关注一件事而忽略其他一切非常有价值。

So this is one reason why guanfacine is now approved, not just for adults with ADHD, but is primarily used in kids aged six to 17 years old for the treatment of ADHD.

因此，这就是为什么胍法辛现在被批准不仅用于患有 ADHD 的成人，而且主要用于 6 至 17 岁儿童的 ADHD 治疗。

Again, with the hope that these kids can take the drug and these circuits can learn how to focus and how to attend to certain things and limit impulsivity and hyperactivity, and then perhaps come off the drugs.

再次，希望这些孩子能够服用药物，并且这些回路能够学习如何集中注意力以及如何关注某些事情并限制冲动和多动，然后也许可以摆脱药物。

Although sometimes, again, people have to stay on them indefinitely.

尽管有时候，人们不得不无限期地继续使用它们。

The other thing about guanfacine is that because it lowers blood pressure and it has this effect of kind of dampening down overall sympathetic arousal, sometimes it is prescribed in conjunction with other ADHD meds.

关于胍法辛的另一件事是，因为它可以降低血压，并且具有抑制整体交感神经兴奋的作用，所以有时它与其他多动症药物结合使用。

So yes, there are kids out there and adults out there who are taking Adderall and guanfacine, or they're taking Vyvanse and guanfacine, and this is where it starts to get into drug cocktails and a bunch of other things that gets everybody a little bit uncomfortable, I think, because the idea of taking one drug to dampen down the side effects of another drug and to offset things and compensate is getting towards what's called polypharmacology.

所以，是的，有些孩子和成年人正在服用 Adderall 和 guanfacine，或者他们正在服用 Vyvanse 和 guanfacine，这就是它开始进入药物鸡尾酒和其他一些让每个人都有点不舒服的东西的地方，我认为，因为服用一种药物来抑制另一种药物的副作用并抵消和补偿的想法正在走向所谓的多药理学。

And I think it's understandable that people would be concerned about that, and yet, again, in viewing this with some of the experts on ADHD, there do seem to be a certain category of children out there and adults who really struggle with the standard ADHD meds, and in that case, guanfacine has provided a certain number of these individuals tremendous relief.

我认为人们对此感到担忧是可以理解的，然而，再一次，在与一些多动症专家一起观察这一问题时，似乎确实有一类儿童和成年人确实在与标准多动症药物作斗争，在这种情况下，胍法辛为其中一定数量的人提供了巨大的缓解。

One note about guanfacine.

关于胍法辛的一点说明。

In no way, shape, or form am I encouraging anyone who's not prescribed guanfacine to take it.

我绝不鼓励任何没有服用胍法辛的人服用它。

But should you know someone who's taking guanfacine off-label in order to improve their focus or enhance any aspect of their biology or psychology, please let them know that it has a profound effect on lowering the tolerance for alcohol, such that even small amounts of alcohol can lead to really serious problems and even potentially death.

但是，如果您认识有人为了提高注意力或增强生物学或心理学的任何方面而超说明书服用胍法辛，请让他们知道，它对降低酒精耐受性具有深远的影响，因此即使少量的酒精也可能导致真正严重的问题，甚至可能导致死亡。

So that's a very serious warning with guanfacine.

所以这是对胍法辛的非常严重的警告。

So today we discussed a lot of different compounds for the treatment of ADHD, and it now should become clear what the general themes of those compounds is.

因此，今天我们讨论了许多用于治疗多动症的不同化合物，现在应该清楚这些化合物的一般主题是什么。

The general theme is that they tend to increase overall levels of arousal and wakefulness, which leads to decreased levels of hyperactivity, impulsivity, and focus.

总的主题是，它们往往会提高整体的觉醒和觉醒水平，从而导致多动、冲动和注意力水平下降。

And on the face of it, that might seem counterintuitive.

从表面上看，这似乎违反直觉。

Raise arousal to reduce hyperactivity and impulsivity?

提高警觉性以减少多动和冲动？

Indeed, that's the case because these compounds, because they act on neuromodulator systems like dopamine and norepinephrine, are effective in creating neuroplasticity.

事实上，情况确实如此，因为这些化合物作用于多巴胺和去甲肾上腺素等神经调节系统，可以有效地产生神经可塑性。

They change the strength of the connections in the neural circuits of the brain that lead to states of heightened focus and reduced impulsivity and reduced hyperactivity.

它们改变大脑神经回路中连接的强度，从而导致高度专注、减少冲动和减少多动的状态。

So we talked about the different mechanisms by which the different medications for ADHD accomplish this, both the typical sort like methylphenidate and Adderall and Vyvanse, and some of the atypical compounds that are now being used in addition, such as modafinil, armodafinil, guanfacine, and Wellbutrin.

因此，我们讨论了治疗多动症的不同药物实现这一目标的不同机制，包括哌醋甲酯、阿得拉和 Vyvanse 等典型药物，以及现在另外使用的一些非典型化合物，如莫达非尼、阿莫达非尼、胍法辛和维布特林。

And where possible, I tried to highlight both the short and long-term effects of these various compounds, and I tried to address some of the major concerns about these compounds, most notably the question of why are we putting so many kids on amphetamine and what is the long-term consequence of that?

在可能的情况下，我试图强调这些不同化合物的短期和长期影响，并试图解决有关这些化合物的一些主要问题，最值得注意的问题是我们为什么让这么多孩子服用安非他命，以及这样做的长期后果是什么？

And throughout today's episode, I tried to highlight both the immediate and long-term benefits, but also the immediate and long-term risks that can exist with these compounds.

在今天的整个节目中，我试图强调这些化合物的直接和长期好处，以及可能存在的直接和长期风险。

Certainly, when taken without a prescription, recreationally, there is a real risk for abuse and addiction, as well as even a risk for psychotic episodes, but also the risks that accompany long-term use of these drugs in people with ADHD.

当然，如果没有处方、为了娱乐而服用，确实存在滥用和成瘾的风险，甚至还有精神病发作的风险，而且多动症患者长期使用这些药物也存在风险。

And yet, it is also clear that not treating the symptoms of ADHD carries significant risk as well.

然而，同样明显的是，不治疗多动症的症状也会带来巨大的风险。

And what's very clear from the scientific and clinical literature, and is covered in a significant amount of detail in the episode that I did about ADHD, which you can find at hubermanlab.com, is that combinations of drug treatments and behavioral protocols seem to surpass either drug treatments or behavioral protocols alone, speaking to the tremendous importance of combining multiple methodologies when treating ADHD and working with a board-certified psychiatrist who really understands ADHD and is really up to date on all the latest scientific and clinical literature.

从科学和临床文献中可以清楚地看出，在我关于 ADHD 的那一集（您可以在 hubermanlab.com 上找到）中，药物治疗和行为方案的结合似乎超越了单独的药物治疗或行为方案，这说明了在治疗 ADHD 时结合多种方法的巨大重要性，并与真正了解 ADHD 并真正了解所有最新科学和临床文献的经过委员会认证的精神科医生合作。

If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.

如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。

That's a terrific zero-cost way to support us.

这是支持我们的绝佳零成本方式。

In addition, please subscribe to the podcast on both Spotify and Apple.

此外，请在 Spotify 和 Apple 上订阅该播客。

And on both Spotify and Apple, you can also leave us up to a five-star review.

在 Spotify 和 Apple 上，您还可以给我们留下五星级的评价。

Please also check out the sponsors mentioned at the beginning and throughout today's episode.

另请查看今天节目开头和整个节目中提到的赞助商。

That's the best way to support this podcast.

这是支持这个播客的最佳方式。

If you have questions for me or comments about the podcast or suggestions about guests you'd like me to include on the Huberman Lab podcast, please put those in the comments section on YouTube.

如果您对我有疑问或对播客有意见，或者对您希望我在 Huberman Lab 播客中加入的嘉宾提出建议，请将这些内容放入 YouTube 的评论部分。

I do read all the comments.

我确实阅读了所有评论。

Not so much on today's episode, but on many previous episodes of the Huberman Lab podcast, we discuss supplements.

今天的节目不多，但在 Huberman 实验室播客的许多以前的节目中，我们讨论了补充剂。

While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like improving sleep, hormone support, as well as focus.

虽然补充剂并不是每个人都需要的，但许多人从它们中获得了巨大的益处，例如改善睡眠、激素支持以及注意力集中。

The Huberman Lab podcast is proud to have partnered with Momentous Supplements.

Huberman Lab 播客很荣幸与 Momentous Supplements 合作。

If you'd like to see the supplements discussed on the Huberman Lab podcast, you can go to livemomentous, spelled O-U-S, so it's livemomentous.com/huberman.

如果您想查看 Huberman Lab 播客上讨论的补充剂，您可以访问 livemomentous，拼写为 O-U-S，即 livemomentous.com/huberman。

If you're not already following me on social media, I am hubermanlab on all platforms.

如果您还没有在社交媒体上关注我，我是所有平台上的 hubermanlab。

So that's Facebook, LinkedIn, Twitter, and Instagram.

这就是 Facebook、LinkedIn、Twitter 和 Instagram。

And on all those platforms, I post about science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the content on the Huberman Lab podcast.

在所有这些平台上，我发布了有关科学和科学相关工具的内容，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客的内容不同。

So again, it's hubermanlab on all social media platforms.

再说一遍，所有社交媒体平台上都是 hubermanlab。

If you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a monthly newsletter in which we distill down the essential points of particular podcasts and we list out toolkits, such as toolkits for sleep, toolkits for neuroplasticity, toolkits for optimizing dopamine, and on and on.

如果您还没有订阅我们的神经网络时事通讯，神经网络时事通讯是一份月度时事通讯，我们在其中提炼出特定播客的要点，并列出了工具包，例如睡眠工具包、神经可塑性工具包、优化多巴胺工具包等等。

All of which is available at zero cost.

所有这些都可以零成本获得。

You simply go to hubermanlab.com, go to the menu, scroll down to Newsletter, and supply your email, and we do not share your email with anybody.

您只需访问 hubermanlab.com，进入菜单，向下滚动到时事通讯，然后提供您的电子邮件，我们不会与任何人共享您的电子邮件。

Thank you for joining me for today's discussion all about pharmaceutical interventions for the treatment of ADHD.

感谢您参加今天关于治疗多动症的药物干预的讨论。

And last but certainly not least, thank you for your interest in science.

最后但并非最不重要的一点是，感谢您对科学的兴趣。