阿得拉、兴奋剂与莫达非尼治疗多动症：短期与长期影响

而这一极其重要的特性就是我们所说的神经可塑性，即大脑和神经系统根据经验发生改变的能力。

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

我曾在《休伯曼实验室播客》中专门制作了多期节目讨论神经可塑性，包括它的定义以及如何在不同发育阶段和成年后激活它。

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.

顺便说一下，你可以在 hubermanlab.com 上通过搜索功能直接搜索 'plasticity' 找到这些节目。

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

但关于今天讨论中神经可塑性的一个关键点是，尽管有多种方式可以诱导神经可塑性，但几乎所有方式都涉及强烈激活某些大脑网络。

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, almost all of them involve strongly activating certain brain networks.

在这种情况下，也涉及某些神经调质的强烈或升高释放。

And in that case, also strong or elevated release of certain neuromodulators.

我们已经讨论过多巴胺和去甲肾上腺素，它们只是众多神经调质中的两种。

Now we've talked about dopamine and norepinephrine, they are but two of many neuromodulators.

其他还包括血清素、乙酰胆碱，每种神经调质在大脑的不同突触处发挥不同的作用。

Others include serotonin, acetylcholine, and each of the neuromodulators does different things at different synapses in the brain.

对于每种神经调质，我们都可以做出一些普遍性的概括。

And there's some global statements that can be made about each of them.

我们之前已经提到过一些，比如多巴胺广泛参与渴望和追求，而去甲肾上腺素则与信号检测以及对环境中、身体内或内在体验中的某些事物赋予注意力或显著性有关。

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

血清素有其他作用，乙酰胆碱也有其他作用。

Serotonin does other things, acetylcholine does other things.

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水平——也就是在此之前它们的水平——出现显著升高时，这种升高往往会促进特定突触的神经可塑性。

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.

因此，现在有必要提醒大家：神经调质不同于神经递质。

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

神经递质是像多巴胺和去甲肾上腺素一样的化学物质，它们在神经元之间释放，正是这些物质直接参与了神经元之间电信号的传递或抑制。

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.

而多巴胺和去甲肾上腺素则调节这种活动，例如使一定量的神经递质产生更强的效果。

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

因此，当我们听到多巴胺和去甲肾上腺素与动机、专注力等联系在一起时，这些说法固然没错，但同样重要的是要记住：当多巴胺和去甲肾上腺素水平升高时，这些区域突触连接被强化的可能性也会增加。

So when we hear about dopamine and norepinephrine and we hear about motivation or focus, etcetera, 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.

这意味着，即使后来多巴胺和去甲肾上腺素水平回落到基线，如果在我们过去的历史中，或者在大脑中某组神经元的历史中，曾经有过较高水平的多巴胺或去甲肾上腺素，那么那些曾经发生过这种升高现象的连接很可能已被强化，因而更容易被激活。

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.

这让我们回到了最初将这些拟交感神经兴奋剂用于发育中ADHD儿童的初衷。

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

它的目的确实是帮助他们集中注意力、减少多动并提升专注力，但同时也旨在帮助负责专注的大脑网络发生神经可塑性，即相关突触得以强化，从而在停药后这些网络仍能更高效地运作。

It was, yes, designed to try and help them focus, to reduce their hyperactivity and help them focus, but it was also designed to help the brain networks that are responsible for focus to undergo neuroplasticity, that is for the synapses involved to strengthen so that those networks could function more efficiently later on, even after cessation of the drug.

这是一个绝对关键的要点，我认为当人们讨论‘我该不该让孩子服用ADHD药物’时，往往忽略了这一点。

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?

或者当孩子从青春期过渡到青少年后期并进入大学时，我该不该让他们停用ADHD药物？

Or should I take my kid off of ADHD meds as they transition from adolescence to their later teen years and into college?

我的意思是，无论是孩子、家长，还是成年人，都不希望在药物带来一系列益处后，这些益处却在日后消失；同样，也没有任何家长或孩子愿意服用一种本可不必使用的药物，因为还有其他途径可以改善神经回路或身体某些系统的功能——我相信，除非别无选择，否则没有人真希望给孩子用药，我希望如此。

I mean, 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, 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, I would hope not.

我也认为，除非绝对必要，否则没有任何孩子愿意被用药。

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

因此，通过像阿得拉、Vyvanse、利他林等药物提升多巴胺和去甲肾上腺素水平，正在引发多种效应。

So increasing dopamine and norepinephrine with these drugs like Adderall, Vyvanse, Ritalin and similar is causing several things.

其中一些效应实际上为父母是否应首先让孩子服用这些药物提供了一些总体性的答案。

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.

显然，他们会在合格精神科医生的仔细指导下进行，我希望如此，而且仅在这些情况下，同时也要考虑孩子是否应该长期服用这些药物。

Obviously, they're going to do that under the careful consult of a qualified psychiatrist, I would hope, and only under those circumstances, but also whether or not the child should stay on those drugs over time.

而我们确切知道的是以下几点。

And here's what we do know for sure.

我曾对文献进行了广泛的检索，以得出一个非常明确的结论：那些被确诊为真正患有多动症（ADHD）、并接受适当剂量如阿得拉、利他林或维万斯等药物治疗的儿童，在童年时期以及成年后，无论是在学业表现、专注能力还是整体结果方面，都表现得更好。

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.

因此，许多人曾疑惑并担忧，童年早期使用这些药物是否会增加日后滥用非法药物或产生药物成瘾的倾向。

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.

而过去十五年，尤其是最近五年（因为大部分数据是在这期间出现的）的研究结果非常明确：那些未得到正确治疗（包括药物和行为干预）的多动症儿童，事实上，药物与行为治疗相结合才是最佳方案。

And it is very clear from the studies that have emerged over the last really fifteen 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.

因此，未接受药物和行为治疗的多动症儿童，在成年后更容易出现非法药物使用和药物成瘾倾向，明白吗？

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, okay?

因此，童年时期不治疗多动症确实存在真正的风险。

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

相反的情况也同样成立：患有多动症并服用拟交感神经药物（即，正如你所听到的，它们属于安非他明类）的儿童。

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.

安非他明就是兴奋剂。

Amphetamine is speed.

不过我应该说，如果他们服用的是哌甲酯、利他林或康泰特之类的药物，那并不是安非他明。

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

尽管如此，它仍然是一种兴奋剂。

Nonetheless, it's a stimulant.

它也是一种拟交感神经药。

It's a sympathomimetic also.

这些孩子在发育期间服用这些药物，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升高。

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.

你可能会说，那这会不会导致他们日后对这些药物产生渴望呢？

And you might say, well, wouldn't that lead to a craving for these things later in life?

但事实似乎并非如此。

And that does not appear to be the case.

事实上，有一些非常出色的神经影像学研究，主要是正电子发射断层扫描研究，我将在节目笔记的字幕中提供相关链接，这些研究表明，早期使用这些药物实际上能导致成年后前脑多巴胺传递能力增强，且所需阈值更低，换句话说，早期使用这些药物能随着时间推移使相关神经回路恢复正常。

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, 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.

再次强调，对于确诊为注意力缺陷多动障碍（ADHD）的儿童，我绝无意暗示所有儿童都应接受这些药物治疗。

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.

这显然不是一个好主意。

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

因此，这一切都凸显了准确诊断ADHD的关键重要性。

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

儿童的诊断标准包含许多方面。

Diagnostic criteria include many things in children.

每类症状——如冲动性、多动性等——都设有九项以上的诊断标准。

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

因此，一位合格的精神科医生会采取多项措施。

So a well qualified psychiatrist will do several things.

首先，他们会对孩子进行细致的诊断评估。

They will, first of all, do a careful diagnostic evaluation of a child.

此外，我们希望他们不仅考虑为ADHD开具合适的药物治疗，还能意识到并推荐其他类型的干预措施，即行为干预。

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.

因此，显然有一些学习工具和孩子可以做的事情，能够帮助他们提高专注力并减少冲动，这些方法尤其能与药物治疗相结合，同时营养和补充剂领域的最新进展也在不断涌现。

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 supplement ation that are constantly coming online.

最优秀的精神科医生会关注ADHD治疗的所有这些方面，而不仅仅是处方药物，还包括行为治疗、营养指导、补充剂，并且随着孩子从一个发展阶段进入下一个阶段，持续更新所有这些治疗方式。

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.

现在，另一个常见问题是：如果孩子在成长过程中接受了这些ADHD药物治疗，他们是否需要终身持续服药？

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

对此的简短回答是：视情况而定。我知道这个答案可能有些令人沮丧，但好消息是，这个问题可以通过一种相当直接的方式进行评估。

And the short answer to this is it depends, and that can be a somewhat frustrating answer, I realize, but the good news is it's something that can be assessed in a fairly straightforward way.

让我们回想一下，使用这些药物治疗ADHD的目的有两个。

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

其一是改善那些使孩子能够专注的神经回路的功能，其二是增强这些回路的强度，从而有效教会这些回路如何学习‘专注’。

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.

换句话说，在某些情况下，这些药物被设计为在使用一段时间后可以逐渐停用，因为它们帮助建立的神经回路已经能够良好运作。

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.

然而，在某些情况下，支撑专注力的神经回路如果没有持续使用药物，将无法达到正常健康生活所必需的功能水平。

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.

那么，在现实世界中这会如何运作呢？

So how would this work in the real world context?

我认为，任何在25岁以下服用过这些药物的儿童、青少年或成年人，都无疑在与我们所称的专注力相关的神经回路中实现了某种程度的神经可塑性。

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.

我想明确一点，我所指的‘专注力’并不存在单一的大脑区域或一组神经回路，因为专注力涉及任务切换，还涉及各种不同的认知活动，具体取决于我们专注的内容，对吧？

And I want to be very clear, there's no single brain area or set of brain circuits for what I'm referring to as focus, because after all, focus involves tasks switching, focus involves all sorts of different cognitive operations, depending on what we're focusing on, right?

专注于运动基本上是一种在不同时间将注意力导向不同位置的练习。

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

专注于学习则是完全不同的专注模式。

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

但关键是，如果一个25岁或以下的人服用了一种能增加多巴胺和去甲肾上腺素的药物，并且假设一切正常——即剂量合适，他们的专注能力得到了提升——那么这些神经回路就会变得更强大。

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, etcetera, those circuits are going to get stronger.

而且，根据我在这集之前访谈过的精神科医生的观点，对于在25岁之前任何时间段服用过ADHD药物的人，与精神科医生讨论逐步停药以评估是否仍需继续服药，是完全合理且值得推荐的。

And it seems entirely reasonable, in fact, it was supported by the psychiatrist that I spoke to prior to this episode, that people who've 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.

我提到‘逐步减量’这个词，是因为如果突然停止服用这些药物，可能会出现戒断反应，因为它们确实会提升多巴胺和去甲肾上腺素水平；尽管它们能增强与专注、情绪和动机相关的神经回路的可塑性，但如果突然完全停药，人会感觉非常不舒服。

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

这种多巴胺水平的下降几乎总会伴随着倦怠、情绪低落、多种不适感，当然还有注意力方面的挑战。

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 and focus.

因此，任何打算停用这些药物，或尝试减少剂量的人，都必须与经过认证的精神科医生保持密切沟通。

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.

同时，来自ADHD专家精神科医生的明确意见是，随着时间推移，逐步减少剂量通常对患者最为理想，对吧？

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, okay?

这引出了关于剂量问题的整体讨论。

And this gets to the whole issue of dosage generally.

我花了不少时间与开这些药的医生交流，他们既为儿童也为成人开药，讨论剂量范围。

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

我不希望从‘应该服用多少’的角度花费太多时间讨论这个问题。

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

事实上，我不希望任何人认为我接下来要说的内容能直接决定他们该服用多少，因为这必须根据个人情况具体确定。

In fact, 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.

但值得注意的是，如果你查阅关于阿得拉和哌甲酯的研究，会发现这些研究中的剂量范围相当广泛。

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.

这是因为一些研究使用了已经服用这些药物的人，并邀请他们参与神经影像学研究。

And that's because some of the studies used people that were already taking these drugs and asked them to participate in neuroimaging studies.

其他研究则首次让受试者服用这些药物，或调整他们的剂量。

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

因此，你将看到研究中探索的药物剂量范围非常广泛。

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

例如，每天服用的阿得拉尔剂量范围从10毫克到40毫克不等。

For instance, you will see anywhere from ten to forty milligrams of Adderall per day.

每天服用的利他林剂量范围从10毫克到60毫克不等。

You'll see anywhere from ten to sixty milligrams of Ritalin per day.

在这里，我们讨论的可能是针对儿童或成人的研究。

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

关于阿得拉尔，你会发现其剂量通常要高得多。

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

部分原因是，如果你还记得，阿得拉尔含有赖氨酸——一个大分子连接在安非他明（一个小分子）上。

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.

因此，Vyvanse的剂量通常在几百毫克范围内，但其中一百毫克的Vyvanse大部分是赖氨酸，并不参与大脑治疗，它只是用来控制药物的缓慢释放。

And so the dosages of Vyvanse tend to be in the hundreds of milligram ranges, but most of that a hundred milligrams of Vyvanse is not going to be the d amphetamine, it's going to be the lysine, doesn't do anything in the context of treating the brain, it's just there to control the slow release.

因此，人们认为一百毫克的Vyvanse大约相当于九毫克的Adderall，以此类推。

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

实际上，很难直接将不同药物的剂量相互转换。

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

在为本集内容准备时，我与一位专注于ADHD的精神科专家交流，他明确指出，预测儿童或成人对任何这些药物特定剂量的反应极其困难。

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

事实上，他向我 anecdotal 地提到，他的一位患者是一名体重300磅的男性，确诊为ADHD，但仅每天服用2.5毫克的Adderall就获得了显著缓解。

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

与此同时，他还有两位患者，是姐妹俩，基因相关，体重在120到140磅之间，她们的ADHD症状在剂量极低时完全无反应，直到剂量被大幅提升才有效。

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

如果我告诉你们这些剂量，我必须提前警告：切勿在未经精神科医生批准的情况下自行尝试这些剂量。

And if I tell you these dosages, I just want to warn you in advance, I'm suggesting anyone explore these dosages without of course the approval of their psychiatrist.

结果发现，这两名年轻女性在达到极高的剂量前对ADHD药物完全无反应——其中一位姐妹每日剂量为180毫克，另一位则达到240毫克，从表面上看，这是极其惊人的高剂量。

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

但这位医生，再次强调，是一位认证的 ADHD 专家，向我证实，这两位患者都没有出现任何不适或副作用，导致她们不愿继续服药。

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.

当然，如此高剂量的阿得拉尔可能会让其他人陷入完全的精神病性发作，甚至可能引发心脏骤停。

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

我的意思是，儿童和成人有效使用的阿得拉尔剂量范围真是令人惊叹。

I mean, it's remarkable the ranges of Adderall that are used effectively in children and adults.

对于其他许多用于治疗 ADHD 的拟交感神经药来说，情况也是如此。

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

当然，一位好的精神科医生会始终根据药物带来的正面效益和症状缓解情况来评估剂量。

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

比如缓解冲动行为、减轻多动、提升专注能力。

So relief of impulsivity, relief of hyperactivity, improvements in ability to focus.

同时，他们也会考虑副作用，即服用特定剂量或任何剂量时可能出现的任何不适或不良反应。

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.

当然，这一切都引出了一个问题：为什么会有如此巨大的个体差异？

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

这是由于人们体内多巴胺或去甲肾上腺素的生成量存在遗传差异吗？

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

看起来，人们需要如此不同的拟交感神经药物剂量来缓解ADHD症状，其主要根本原因在于个体体内代谢这些药物的酶或酶水平不同，这些酶在大脑和身体中都会发挥作用。

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.

遗憾的是，目前没有任何简单的血液检测、唾液检测或任何其他检测方法可以预测个体对这些药物的反应。

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.

因此，评估剂量最合理且安全的方式是从最低有效剂量开始，仅在必要时逐步增加，以实现积极疗效，同时密切关注可能出现的任何副作用。

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.

在讨论像阿得拉、利他林和维万斯这类药物的长期影响时，一个时常出现的问题是：它们是否会负面影响身高、生长或其他方面的发育。

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.

这是一个合乎逻辑的问题，因为毕竟这些药物本质上是在模拟身体的应激反应。

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

如今，大多数人已经知道，虽然短期应激有助于我们调动免疫分子以抵御感染，增强视觉专注力和应对威胁的生存能力，但长期持续处于应激状态，却会削弱免疫系统的有效性，甚至可能导致某些形式的脑部退化。

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, 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.

尽管关于ADHD儿童身高的纵向研究并不多，而且我们永远无法确切知道，如果不使用药物，一个人本会长到多高——因为我们无法进行完美的对照实验，即便在同卵双胞胎实验中也是如此，而其中真正符合‘一个双胞胎接受ADHD治疗，另一个未接受’的案例也极为稀少，等等。

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, etcetera.

但这是我们所知道的。

But here's what we know.

事实上，只要剂量保持在适当范围内，在发育期间使用拟交感神经药物并不会限制总体身高。

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.

事实上，如果你查看数据，会发现接受ADHD药物治疗的儿童相比同龄人，其体重指数（BMI）略高一些。

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 BMI's, body mass indexes, compared to age matched peers.

当然，体重指数并不一定与身高相关，对吧？

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

一个人可能没有达到应有的身高，但体重却更重，这可能是由于骨骼、脂肪、肌肉或三者兼有所致。

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

但我们知道，在发育期间合理使用ADHD药物并不会以任何整体方式抑制发育。

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

它不会阻止身体成熟，也不会导致体重下降或整体生长受损。

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

尽管如此，长期交感神经系统活动的升高仍存在一定风险。

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

人们一直担心的一个主要风险是心血管风险。

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

这完全说得通，对吧？

And this makes perfect sense, right?

当你增加交感神经系统的活性时，血压会升高，心率会加快，在某些情况下还会增加外周出汗，这些都是我们与压力相关的反应。

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.

因此，你可以想象，一个患有ADHD的儿童或成人每天服用这些拟交感神经药物，即使剂量控制在不会引起任何明显不良反应的范围内。

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.

他们不会感到痛苦，只是觉得注意力更集中了，但人们总会好奇体内究竟发生了什么。

So they're not feeling miserable, they're just feeling like they can focus better, but one always wonders what's going on under the hood, so to speak.

据我所知，有一项大型研究对此进行了探讨，而该研究的结论很难归为单一类别。

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.

研究确实指出心血管风险有轻微增加，但结果并未显示任何足以让研究作者警告患者停药或劝阻人们停药的显著风险——前提是这些药物由经过认证的医生为ADHD患者开具，并使用适合该患者的适当剂量。

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.

尽管如此，我认为这一切再次强调了使用最低有效剂量的重要性。

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

因此，如果你或你的孩子正在服用注意力缺陷多动障碍药物，那么理所当然应该尽可能采取其他措施来改善心血管健康，或至少避免增加额外风险。

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.

这些显然是些显而易见的做法，比如避免吸烟或使用尼古丁电子烟，鼓励规律锻炼，以及其他类似的行为。

So those are going to be the obvious things like avoiding smoking or vaping nicotine, regular exercise is going to be encouraged and things of that sort.

这引出了另一个经常被问到的问题，每当提到阿得拉或利他林时都会出现：那么酒精呢？

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

你知道吗，如果在服用这些药物的同时或不同时间饮酒，会不会有问题？

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

服用苯二氮䓬类药物会不会有风险，等等等等？

Is taking benzodiazepines going to be a problem, etcetera, etcetera?

对此有一个非常明确的答案：酒精，尤其是在儿童中，但成人也是如此，最好完全避免饮用。

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.

我曾经专门做了一期节目讨论酒精，其中详细探讨了相关数据和研究。

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

如果你曾听说适量饮酒，尤其是红葡萄酒，比完全不喝酒更健康，那完全是错误的。

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

抱歉，这并不正确。

Sorry, it's not true.

大多数非酗酒的成年人每周饮用两杯酒可能仍处于健康安全范围内，尽管零杯比两杯更好，一旦超过两杯，就会开始对多个系统产生影响，包括增加癌症风险，尤其是大脑神经元的损失和退化风险。

Most adults who are not alcoholics can probably have up to two drinks per week and still be on the safe side of health, although zero is better than two, and once you get past two, you start seeing effects on various systems, including increased cancer risk, especially brain neuron loss and degeneration risk.

我在关于酒精的那期节目中详细介绍了所有这些数据，你可以在 hubermanlab.com 上找到。

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

将酒精与拟交感神经药结合使用，尽管它们在大脑中的通路完全不同——拟交感神经药会增强交感神经系统活性，而酒精则恰恰相反，它会抑制这种活性。

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, it's depressing it.

但所有数据都表明，将酒精与芬他明、阿得拉、利他林或任何类型的安非他明类药物结合使用，对大脑和身体的损害，会比单独服用这些药物更严重。

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.

换句话说，更直接地说：如果你正在服用我们之前讨论的用于治疗注意力缺陷多动障碍的药物，或者出于任何其他原因服用这些药物，你都应该避免在任何时候饮酒，并且应避免使用苯二氮䓬类药物及类似物质，除非它们由你的医生开具处方。

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.

在本节目播出前，我在社交媒体上征集了关于阿得拉等问题的提问。

In advance of this episode, I put a call out on social media for questions about Adderall, etcetera.

我收到了大量关于这些药物是否会影响人体激素系统，特别是是否影响生殖系统的问题。

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.

我还收到了一些问题，询问这些药物是否会影响性行为、性欲或类似方面。

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

在查阅文献后，我可以告诉你们的是，不幸的是，关于这些药物对内分泌或激素系统长期影响的研究非常少，但我们确实知道一些确定的事情。

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, but we do know a few things for sure.

首先，当你长期提高交感神经系统的活性时，很可能会增加皮质醇的水平。

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.

皮质醇是一种压力激素，但它也在你的身体中发挥着一些非常重要的积极作用。

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

事实上，你希望在一天的早些时候释放皮质醇吗？

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

你并不希望在一天的晚些时候释放过多的皮质醇。

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

这实际上与服药的时间和作息安排有关。

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

这同样需要你与你的精神科医生，或你孩子的精神科医生共同商讨确定。

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

但治疗多动症的药物有这么多不同种类，原因之一是每种药物的作用时间不同。

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.

所以利他林的作用时间非常短，这听起来可能不太好，因为你需要在一天中多次服用。

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

但从睡眠的角度来看，考虑到夜间皮质醇水平应保持较低，而这些药物会升高皮质醇，以及睡眠对儿童和成人心理健康、身体健康和表现至关重要，这一点就显得很重要。

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.

睡眠负责生长，也是神经可塑性发生的时候，它对健康至关重要。

It's responsible for growth, it's when neuroplasticity happens, it's just so vitally important.

我们所讨论的许多药物会严重妨碍人入睡和保持睡眠的能力。

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

因此，像利他林这样的短效药物反而具有吸引力，因为它可以在早上服用，仍能在夜间入睡；或者早上、下午服用，甚至在某些情况下晚上再服一次，但仍能顺利入睡。

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.

而像阿德拉这样的长效苯丙胺制剂——你服用维思通时获得的就是这种效果——对某些人来说会抑制睡眠。

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.

他们可能会获得稳定的情绪提升、注意力改善和多动减少，但晚上却可能很难入睡。

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.

而阿得拉尔的作用时间介于利他林（作用时间短）和维拉辛（作用时间长）之间，或许对某些人来说是最佳选择：他们可以在早上服用，剂量较低，可能下午再服一次低剂量，但仍能顺利入睡。

And Adderall having a somewhat intermediate time course of action between Ritalin, which 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.

但我曾与一些人交谈，也咨询过一位ADHD临床专家，他们告诉我，有些人早上6点只服用2.5毫克的阿得拉尔，当晚11点仍难以入睡。

But I've spoken to people and I've spoke to this clinician expert in ADHD who told me that some people will take as little as two point five milligrams of Adderall at 6AM and have a hard time falling asleep later that night at 11PM.

因此，人们对这些药物的敏感性差异极大，导致对剂量、服药时间以及选择哪种药物的个体需求也截然不同。

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.

那么，这与激素、性欲和生殖有什么关系呢？

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

皮质醇本身是一种激素。

Well, cortisol itself is a hormone.

它在大脑中既可以作为激素，也可以作为神经递质发挥作用，但大部分情况下，它在大脑和身体中主要作为激素起作用，并发挥多种功能。

It can act as a bit of a hormone and a neurotransmitter in the brain, but for the most part, it's acting as a hormone in the brain and body, and it does a number of things.

首先，它可以增强你的专注力和警觉性。

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

它可以激活你的免疫系统。

It can activate your immune system.

我知道那些免疫学家听到我说‘激活免疫系统’时都会皱眉。

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

你的免疫系统一直在进行各种活动，所以它始终处于活跃状态，就像你的神经系统始终活跃一样，但具体来说，它可以放大或动员释放抗炎分子，以对抗不同类型的细菌、病毒和真菌感染。

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

它在许多方面都发挥着积极的作用。

It's doing an enormous number of positive things.

它还参与情绪的调节。

It's also involved in setting mood.

它与甲状腺激素通路有相互作用。

It has interactions with thyroid hormone pathways.

我曾经做过整个节目专门讨论皮质醇和皮质醇的调节。

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

用一个非常宽泛的视角简要概括一下，早晨早期皮质醇水平较高是有益的，而到了一天结束时则应逐渐下降。

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.

事实上，傍晚时段皮质醇水平升高与抑郁症状密切相关。

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

这一发现由我的同事大卫·斯皮格尔和罗伯特·萨波尔斯基在斯坦福大学医学院完成，但这并不意味着皮质醇是坏的，而是说皮质醇释放的时间点至关重要。

This was demonstrated by my colleagues, David Spiegel and Robert Sapolsky at Stanford School of Medicine, but that is not to say that cortisol is bad, it's to say that the timing of cortisol release is key.

那么，这些拟交感神经药物会干扰内分泌系统吗？

So do these sympathomimetic drugs disrupt the endocrine system?

嗯，它们可能会。

Well, they can.

无论你是在白天早期还是晚期服用用于治疗注意力缺陷多动障碍的拟交感神经药物，只要你处于高度清醒和警觉状态，就很可能在一天后期经历皮质醇水平升高。

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.

因此，即使你喜欢在晚上和夜间学习并需要集中注意力，也务必尽量限制傍晚和夜间的整体警觉性和压力水平，因为日复一日、周复一周、年复一年地如此，确实会扰乱内分泌系统的其他激素。

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.

再次强调，这是因为皮质醇会与甲状腺激素、睾酮和雌激素相互作用。

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

事实上，皮质醇在许多方面会与睾酮及其他所谓的类固醇激素竞争，甚至可能占据优势。

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

请记住，皮质醇本身也是一种糖皮质激素。

Remember cortisol itself is a corticosteroid hormone.

当我们听到‘类固醇’这个词时，人们常常只想到运动员和体育中的类固醇滥用，但实际上类固醇激素包含许多对我们有益的不同类型激素。

So when we hear the word steroids, oftentimes people just think about athletes and steroid abuse in sports, but steroid hormones includes a lot of different types of hormones, which are good for us.

我们体内的内源性类固醇激素对各种功能至关重要，比如活力、繁殖等。

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

总体而言，这一过程是通过胆固醇分子来合成睾酮、皮质醇和雌激素。

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

如果我们产生过多的皮质醇，就在很大程度上减少了我们体内睾酮的总量或活性水平。

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

这并非完全那么简单，但我们能有把握地做出这一陈述。

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

例如，如果你在一天中因某种压力事件而短暂地升高了皮质醇水平，这并不会抑制你的睾酮水平。

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.

事实上，它可能还会在一定程度上提升你的睾酮水平。

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

然而，如果你的皮质醇水平长期处于高位，确实很可能抑制你的总睾酮或游离未结合形式的睾酮。

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.

由此产生的下游效应包括性欲下降、肌肉和骨质流失，以及与睾酮相关的心理和生理功能的全面衰退。

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.

这对男性和女性都适用。

This is true for both males and females.

同样的情况也适用于雌激素。

And the same thing could be said for estrogen.

然而，我们无法断言某种治疗注意力缺陷多动障碍（ADHD）的药物是否会，例如，阻止女性排卵。

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.

这可能是由于皮质醇长期升高所致，但并没有直接关联——至少据我所知，目前没有任何研究显示服用阿得拉（Adderall）的人会出现排卵周期不规律或完全停经的情况。

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.

我认为根本没有任何证据表明服用阿得拉或其他拟交感神经药物治疗ADHD的人睾酮水平会整体降低。

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.

事实上，你可以想象许多相反的情况：一个患有ADHD的儿童、青少年或成年人，在服用药物改善症状后，能够更专注并取得更多人生成就。

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.

我们知道，幸福感会影响多巴胺，反之亦然；睾酮水平、生产力以及实现目标本身，也会反过来影响激素系统。

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.

因此，每当讨论激素或有研究显示做X或不做Y会影响某种激素水平时，我们必须非常谨慎，确保我们讨论的是因果关系，因为这些激素之间存在着极其复杂的相互作用。

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.

然而，我们可以做出一个非常概括性的陈述：当你长期处于压力状态时，这对你的免疫系统、激素系统，以及大脑和身体的其他任何系统都不是有利的条件。

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.

因此，使用这些药物治疗ADHD绝不能以牺牲这些其他关键生物系统为代价。

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

另一个常见问题和担忧是，儿童，以及相应的成年人，在服用ADHD药物时，是否会被 predisposed（易感）于精神病或其他形式的成瘾。

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.

之前我们讨论过成瘾风险，核心结论非常明确：那些接受适当治疗的儿童和成年人——即在经过认证的合格精神科医生监督下，使用适当剂量的合适药物——成年后对其他物质形成成瘾的风险更低，或总体上成瘾风险更低。

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.

我想很多人也想知道，这些服用ADHD药物的儿童和成年人是否会对自己所服用的药物本身产生依赖。

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.

这是一个有点难以厘清的问题。

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

每当一个人停止服用药物，甚至逐渐减停一种能让自己感觉更好的药物时，都会经历两组效应。

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're going to experience two sets of effects.

这两组效应常常相互混淆。

And these two sets of effects are often confounded with one another.

一组是戒断效应。

One is the withdrawal effects.

也就是停用药物后，使人感觉比基线状态更差的影响。

So the effects of removing the drug that makes somebody feel less good than baseline.

例如，一个服用ADHD药物直到青少年晚期或二十岁出头的孩子决定逐渐停药，他们在减量过程中或当剂量降至零时感到状态糟糕、头脑昏沉、无法集中注意力，甚至情绪低落，但这些症状究竟是戒断反应，还是因为大脑中原本被药物激活的系统不再以原有方式被激活所导致的结果，尚不明确。

So for instance, a kid that takes ADHD meds until their late teens or early twenties decides they're going to taper off, they do that, and they're feeling lousy during the taper or when they reduce their dosage to zero, their foggy brain, they can't focus, that you feel a little bit depressed mood, 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.

我知道对你们中的一些人来说，这可能看起来像是同一件事，但其实未必如此。

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

最贴切的类比可能是宿醉，对吧？

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

如果一个人某晚饮酒过量，第二天早上就会宿醉，感到状态很差。

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

这确实是酒精戒断的表现，但当他们从宿醉中恢复后，会发现清醒状态其实感觉还不错。

It is actually a withdrawal from alcohol effect, but then when they recover from the hangover, they realize that their sober state feels pretty good.

这显然不像喝酒时的感觉，但这种清醒状态并不是一种戒断状态，明白吗？

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

如果我们观察停用或逐渐减少ADHD药物的情况，会有一段戒断症状期，但真正关键的问题是，当人们度过这些戒断症状后，他们的感觉如何？

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?

因此，这是一个需要强调的重要问题。

So that's an important issue to highlight.

现在，关于精神病，这是一片非常有趣且重要的研究领域。

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

首先，任何苯丙胺类药物，无论是右苯丙胺、左苯丙胺，还是哌甲酯（如利他林），都可能引发精神病。

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

现在，有许多不同的因素会使人更容易出现精神病。

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

如果一级亲属曾出现过精神病发作，无论是精神分裂症还是双相情感障碍发作，这无疑是强烈的易感因素。

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

当然，如果个体本人曾有过精神病发作，那就是最强烈的易感因素了。

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

因此，如果一级亲属患有精神分裂症或双相情感障碍（有时也称为双相障碍，如今也常简称为双相），这将显著增加出现精神病发作的风险，尤其是在服用拟交感神经药物如安非他明或哌甲酯（利他林）时，这种风险会进一步升高。

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.

接下来的问题是，如果某人因服用这些药物（无论是否为治疗ADHD而处方）而出现精神病发作，那么在停药后，这些精神病症状是否会消失？

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?

文献中似乎存在一种以药物为依据的分歧：服用利他林（哌甲酯）并出现精神病发作的人，通常——虽然并非总是——在停用哌甲酯后，精神病发作会停止。

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.

并非总是如此，但大多数情况下症状会消失。

Not always the case, but most oftentimes it will cease.

然而，对于那些具有精神病倾向的人，或者即使他们自己并未意识到有这种倾向，但服用了阿得拉（Adderall，由D型和L型安非他明组成）的人，他们可能会出现持续时间很长的精神病发作，即使在停药后仍可能持续。

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.

虽然这听起来可能令人震惊且非常可怕，确实如此，但考虑到阿得拉中含有大量D型安非他明，而D型安非他明是极强的多巴胺提升剂，我们或许不应太过惊讶。

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.

因为每当在具有精神病倾向的人体内强力提升多巴胺水平时，都会使整个系统更倾向于发生精神病。

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.

现在也是时候谈谈甲基苯丙胺了。

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

再次强调，冰毒被视为非法药物，一种滥用药物。

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

它导致了大城市乃至非大城市和农村地区街头随处可见的诸多不幸与悲剧。

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 and rural areas.

它对健康有各种负面影响，包括口腔健康和心血管健康。

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

它对血清素神经元具有神经毒性，会杀死血清素神经元，这一点是明确无疑的。

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

它也会杀死多巴胺神经元，这一点也是明确无疑的。

It kills dopaminergic neurons, that is absolutely clear.

冰毒造成诸多问题的一种方式，包括对身体的影响、滥用潜力、成瘾潜力，以及它既能诱发有精神病倾向者的精神病，也能在无精神病倾向的个体中引发精神病。

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.

所有这些都表明，冰毒简直就是一种彻头彻尾的糟糕药物。

And all of this points to methamphetamine just being a terrible drug all around.

然而，如果你还记得本集开头提到的，有一种处方形式的甲基苯丙胺，但其用途极其有限，或许最好不在这里讨论，因为其临床用途非常狭窄。

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.

我设法采访了一位专家。

I managed to talk to one expert.

这是一位获得认证的精神科医生，专长于注意力缺陷多动障碍（ADHD），同时也非常熟悉甲基苯丙胺和各种ADHD药物诱发的精神病症状，以及那些具有易感性的人群。

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 and people who have the predisposition.

他们明确指出，任何属于苯丙胺类的拟交感神经ADHD药物，比如阿得拉（Adderall）和长效阿得拉、纯右旋苯丙胺（Dexedrine）或任何含苯丙胺的变体，都会增加有精神病易感性人群诱发精神病的风险。

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, it'll 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.

但他们向我保证，在适当处方和安全剂量下，服用这些药物的人群中精神病的总体发生率仍然较低，与普通人群相比并没有显著更高，尽管风险有所增加，但并不严重。

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

他们还强调，哌甲酯（利他林）诱发精神病的潜力较低，虽然并非为零，但比苯丙胺类拟交感神经药物诱发精神病的风险要低。

And they also highlight the fact that methylphenidate Ritalin carries a lower potential for inducing psychosis, not zero, but a lower level of inducing psychosis than for the amphetamine type sympathomimetics.

现在，有一个例外是Vyvanse，也就是我们前面提到的长效右旋苯丙胺。

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

Vyvanse所释放的长效右旋苯丙胺似乎具有某种保护作用，但这并不意味着Vyvanse完全没有滥用或成瘾的可能。

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.

我从同一位专家那里得知，确实有患者试图提高Vyvanse的吸收速率和右旋苯丙胺的释放速度，以获得比单纯长效释放更强的快感。

I was told by this 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.

但他们确实向我保证，Vyvanse似乎与较少的精神病发作以及更低的滥用和成瘾潜力相关，这并不是说它是一种完全安全的药物，但这一点确实凸显了：某种药物所引起的多巴胺和去甲肾上腺素释放的动力学或时间进程，与其滥用潜力、成瘾潜力以及诱发精神病发作的潜力高度相关。

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

而这正是讨论甲基苯丙胺特别相关的地方。

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

甲基苯丙胺之所以在成瘾潜力和诱发精神病发作方面如此危险，首先是因为它释放的多巴胺量极大——比我们之前讨论的其他药物高出五倍，其次是因为其峰值出现得极为迅速。

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.

无论人们是通过鼻吸、口服，还是尤其是静脉注射，其起效都极快；而甲基苯丙胺由于使多巴胺迅速大量升高，随后峰值又迅速回落，甚至低于初始的基线水平，这正是甲基苯丙胺在成瘾和诱发精神病发作方面如此危险的原因之一。

It's a very fast onset and that's true whether or not people are snorting it, whether or they're taking it orally or especially if they inject it intravenously, but meth, because it increases dopamine so fast into 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, that's one of the reasons why methamphetamine is so dangerous in terms of addiction and in terms of psychotic episodes.

这又回到了我们之前在《休伯曼实验室播客》中多次讨论过的多巴胺动力学问题，我曾做过两期关于多巴胺的节目，可以参考。

Now, 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.

其中一期叫《多巴胺、动机与驱动力》，主要讲的是多巴胺及其调节方式。

One is called Dopamine Motivation and Drive, which is all about dopamine and regulating dopamine.

另一期则是关于如何优化多巴胺。

And the other one is about optimizing dopamine.

这期内容更偏向于实用工具包类型。

It's more of a toolkit focused episode.

这两期节目都可以在 hubermanlab.com 上找到，但与我们当前讨论相关的核心要点是：多巴胺的问题不仅在于达到的绝对水平，更在于这些多巴胺水平升高的持续时间。

Both of those you can find at hubermanlab.com, but the general takeaway 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.

因此，尽管 Vyvanse 是右旋安非他明，效力相当强（虽然不如甲基苯丙胺），它能有效提升多巴胺和去甲肾上腺素，但其释放过程是长效缓释的，这降低了它的整体滥用潜力，因为它通常不会产生强烈的即刻欣快感然后迅速跌至基线以下。

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, 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.

很多人听到‘它会大幅提高多巴胺并长时间维持’，就会以为这意味着你会持续欣快十六小时，但事实并非如此。

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 sixteen hours, but that's not the case.

在多巴胺的问题上，关键在于峰值有多高，以及这个峰值是稳定还是会再次下降。

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 it comes down again.

至于精神病发作或成瘾潜力，似乎任何能迅速提升多巴胺、又迅速使其下降的药物或行为，都具有极高的成瘾、滥用和诱发精神病发作的风险。

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.

因此，我之所以并列讨论这两点。

So that's why I'm talking about these two things in parallel.

现在你应该很清楚，为什么 Vyvanse 的成瘾和滥用潜力较低，且诱发精神病发作的可能性也至少更低。

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.

同时，你也应该明白，对于儿童时期或成年后没有患 ADHD 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——如哌甲酯、利他林、阿德拉、Vyvanse、右旋苯丙胺，尤其是甲基苯丙胺——神经影像学研究显示，这些人会经历巨大的多巴胺水平飙升。

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.

他们对这些药物不熟悉，因此多巴胺的升高对他们来说简直是天文数字。

They're not familiar with these drugs, so the increases in dopamine are just cosmic for them.

他们会体验到强烈的欣快感。

They experience a lot of euphoria.

即使剂量很低，这种欣快感也伴随着一种他们从未真正感受过的极度专注。

Even if the dosages are low, the euphoria is associated with a very heightened degree of focus they've never really felt before.

这里我说的是许多非处方和娱乐性使用阿得拉尔及其类似药物的情况。

Here, what I'm talking about is a lot of the recreational and off prescription use of Adderall and things like it.

我们知道，这会引发对这种感觉和物质的滥用与成瘾风险，同时也增加了未来出现精神病发作的可能性，明白吗？

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, okay?

换句话说，患有注意力缺陷多动障碍的儿童，或患有注意力缺陷多动障碍的成年人，如果被开具这些药物并服用一段时间，反而比那些首次或偶尔经历多巴胺长期或急剧升高的人，面临更小的相关风险。

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.

而任何未经处方使用这些药物、并决定‘我想更专注’或‘我要用它连续几天不睡觉’的人，

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.

换句话说，以娱乐或增强表现为目的使用这些药物，由于在毫无准备的情况下服用这些药物所导致的多巴胺释放幅度和时间进程，其成瘾风险要高得多。

In other words, using it recreationally or using it for 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.

因此，我强烈建议所有人，除非医生已为你开具处方用于治疗ADHD，否则不要使用我迄今为止讨论的任何化合物。

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.

现在，我肯定有人在后台喊道：等等，如果一个孩子因为被诊断为ADHD而服用这些药物，他们第一次服用时，会产生巨大的多巴胺反应。

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.

或者，如果一个成年人去看精神科医生，说‘我注意力难以集中’，医生为他们开了这类治疗ADHD的药物，他们服用后也会产生巨大的多巴胺反应。

Or if an adult goes in and talks to their psychiatrist and says, know, 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.

这难道不会引发与滥用这些药物的人相同的后果吗？

Isn't that going to set in motion all the same things that somebody who is using these drugs recreationally would have?

确实，这正是许多精神科医生会从极低剂量、甚至最低可能剂量开始的原因，以观察患者对低剂量的反应，之后再根据情况决定是否逐步增加剂量。

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，他们甚至可能根据个体对药物的敏感程度，进一步降低剂量。

In fact, they might even bring it down further depending on how sensitive somebody is to the drug.

但同样重要的是，ADHD儿童或ADHD成人反复服用这些药物，会导致每次的多巴胺峰值逐渐降低——这并不意味着患者对药物完全失去敏感性，而是系统通过所谓的稳态可塑性，即通常所说的药物耐受性，实现了平衡。

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, 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, sometimes referred to broadly as habituation to a drug.

但大脑和身体中存在一些系统，能够调节神经元之间的连接，使得如果多巴胺和去甲肾上腺素在一段时间内持续高于基线水平，系统会自我调节，使神经元之间的连接增强，从而不再需要如此大幅度的多巴胺和去甲肾上腺素升高。

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 dopamine and norepinephrine.

我意识到这听起来可能有点专业，但我的意思其实是，一个人第一次服用药物时的反应，与日复一日持续服用同一种药物时的反应截然不同。

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.

这引出了另一个如今很少被讨论、但却非常重要的问题。

This gets to another issue, which is not discussed that often these days, but that is really important.

如果你回溯这些拟交感神经药最初的临床文献，会发现最初使用它们治疗儿童多动症时，建议儿童不要每天服用这些药物。

If you go back to the original clinical literature on these 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.

我并不是建议孩子停药休息，因为我不是临床医生，也不推崇任何特定的剂量或用药方案；但当我再次与一位专攻多动症的精神科专家交谈时——他不久后将作为嘉宾做客本播客——他告诉我，许多这类药物原本设计为儿童在上学周服用，周末停药，或在学年期间服用，同时在暑假期间也停药。

Now, I'm not recommending that kids take drug holidays because I'm not a clinician, I'm not promoting any specific dose or dosing regimen, 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.

而如今，孩子们几乎从不遵循这种服药模式，其背后有着有趣的社会学和经济原因。

And that these days rarely if ever is that the pattern of intake that these kids are following And why that is, has interesting sociological and financial explanations.

我并非暗示任何阴谋论，但这种用药模式在近年来逐渐被忽视，我认为这一点非常值得探讨。

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, but I think is really interesting.

事实上，这种用药方式也曾被支持用于成人多动症的治疗。

And it's something that actually was supported for the treatment of adult ADHD as well.

同样，一次性服药与连续五天服药后周末停药，再与日复一日、年复一年持续服药，这三者在生物学和神经可塑性上的反应是截然不同的。

Again, there's 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.

在为本集节目查阅文献时，我承认，要找到关于服用阿德拉或维万斯等药物的长期影响等问题的答案，实在令人眼花缭乱。

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, etcetera.

事实上，关于服用药物治疗ADHD的长期影响的大部分文献，都集中在甲基苯丙胺（利他林）上。

In fact, most of the literature on the long term effects of taking drugs to treat ADHD has focused on methylphenidate on Ritalin.

关于维万斯和阿德拉的研究确实存在，而我将在节目笔记的标题中主要链接这些研究，因为如今人们对这些药物的兴趣最高。

There are studies on Vyvanse and Adderall, 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.

之所以许多研究都聚焦于甲基苯丙胺（利他林），主要是因为它曾是最早用于治疗ADHD的药物之一。

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.

因此，就探讨接受ADHD药物治疗的儿童的长期影响而言，这些孩子如今已成年，因而可以进行神经影像学检查和评估。

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.

而许多被处方阿德拉、维万斯或类似药物的儿童，尚未到达我们能直接回答这一问题的生命阶段。

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.

有一些研究，我在今天的描述中已明确包含这些研究，特别是我前面提到的结果——那些长期服用ADHD药物（数月到数年）的儿童或成人，其执行功能有所改善的研究，这些研究确实同时包含了阿德拉、维万斯和甲基苯丙胺。

There are a few studies and I've made it clear to include those studies in my description of results today, in particular, the results 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, those studies did include both Adderall and Vyvanse and methylphenidate.

我仍会提供这些研究的链接，但总体而言，我们目前对这些药物长期影响的了解，主要基于甲基苯丙胺的研究。

And again, I'll link to those studies, 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.

我想花一点时间谈谈一些完全不属于安非他明类、但如今越来越多地用于治疗儿童和成人多动症的化合物。

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.

这一类非安非他明类多动症治疗药物中，主要药物是莫达非尼，它也以其商品名普罗瓦吉尔为人所知。

The major drug in this category of non amphetamine treatments for ADHD is modafinil, which is also called by its commercial name, Provagil.

它有一个变体叫阿莫达非尼，商品名为努瓦吉尔。

There's a variant on this, which is Armodafinil, goes by the brand name Nuvagil.

莫达非尼和阿莫达非尼之间的主要区别，除了化学结构上略有不同外，是莫达非尼先上市，阿莫达非尼是这一类药物的第二代产品，而且莫达非尼通常价格非常昂贵。

The major difference between Modafinil and Armodafinil, aside from having a slight chemical difference is that Modafinil was released first, Armodafinil is the second in the generation of these drugs and modafinil tends to be very expensive.

这也是为什么有些人难以负担的原因。

That's one of the reasons why it's prohibitive for some people to take.

它每片价格可能高达25美元或更高，每月花费超过一千美元。

It can be as expensive as $25 a pill or more, so more than a thousand dollars per month.

而阿莫达非尼则便宜得多。

And armodafinil tends to be far, far less expensive.

我曾与几位专家探讨过这两种药物是否存在真正的差异，他们表示没有，但服用这些药物的患者出于各种原因——无论是安慰剂效应还是其他——却报告称确实存在差异。

I've talked to a couple of 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.

当我提到安慰剂时，我绝不是说这些药物只是起到安慰剂的作用。

When I say placebo, I in no way mean that these drugs are just acting as placebo.

我只是想说，人们往往对某些药物非常依赖，无论是品牌药还是仿制药，哪种对他们更有效。

I just mean that, you know, people tend to get very attached to certain drugs and whether or not the brand name or the generic version works better for them.

关于这一点，有很多说法和传闻。

There's all sorts of lore about this.

事实上，有很多人强烈认为品牌药阿得拉（Adderall）比仿制阿得拉对他们更有效。

In fact, there are a lot of people out there who strongly feel that brand name Adderall works better than generic Adderall for them.

也有很多人对文拉法辛（Vyvanse）持有同样的看法。

There are a lot of people out there who say the same thing about Vyvanse.

还有很多人为利他林（Ritalin）以及各种药物表达了类似的观点。

There are a lot of people out there who say the same thing about Ritalin and all sorts of drugs.

这些说法是否真实，尚不明确。

Whether or not that's true or not is unclear.

但可以肯定的是，仿制药在药片或胶囊中使用的赋形剂和其他成分可能与品牌药不同，这会影响药物的释放速率和代谢等。

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, etcetera.

但很多这种情况只是劳拉的个人体验。

But a lot of this is just Laura.

事实上，我查阅了文献，试图找到任何确凿的证据，证明仿制阿得拉（Adderall）不如品牌版阿得拉有效或效力更强。

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.

尽管有成千上万的人持相反观点，但我未能找到任何经过同行评审的已发表数据支持这一说法。

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.

所以谁知道呢？也许这是一种所谓的信念效应，也许确实存在实际差异。

So who knows, maybe it's a belief effect as it's called, maybe there's a real difference there.

如今，莫达非尼和阿莫达非尼被用于治疗各种日间嗜睡问题。

Nowadays, modafinil and armodafinil are prescribed for a huge range of daytime sleepiness issues.

我们之前谈到了发作性睡病，但也有一些人因痴呆或术后麻醉导致日间嗜睡。

And we were talking about narcolepsy, but there are also people who suffer from daytime sleepiness related to dementia, daytime sleepiness related to post surgery anesthesia.

因此，存在这样一种情况：人们做完手术后，前几天感觉好转，但随后却发现无法恢复正常的清醒水平。

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，有时会开这种药，帮助患者恢复正常的清醒状态。

So it's prescribed sometimes to try and get people back into a normal state of wakefulness.

它也被用于中风后的创伤性脑损伤。

It's been prescribed for traumatic head injury after stroke.

所有这些处方用途都必须由认证医生执行。

Again, all of these prescribed uses have to be carried out by a certified physician.

你真的不希望擅自滥用莫达非尼或任何其他处方药。

You really don't want to start cowboying the use of modafinil or modafinil or any other prescription drug for that matter.

我必须说，在今天这期节目中讨论所有这些药物时，我对这些药物除了莫达非尼之外，没有任何第一手经验。

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.

早在2017年，我因时差和旅行海外演讲时的日间嗜睡问题，被开了极低剂量的莫达非尼。

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.

因此，我拿到的是25毫克的莫达非尼片剂。

So armodafinil was given to me in a twenty five milligram tablet.

医生建议我服用半片甚至四分之一片，所以我从四分之一片开始。

It was advised to me that I take a half or even a quarter of that, so I started with a quarter.

我信奉最小有效剂量的原则。

I'm a believer in minimal effective dose.

我本人对大多数药物都比较敏感，因此我服用了我测量出的五到七毫克的阿莫达非尼，所感受到的效果非常显著。

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.

它确实缓解了白天的嗜睡感。

Certainly it relieved any daytime sleepiness.

事实上，它让我在大约四到六小时内感到异常清醒。

In fact, it made me feel extremely alert for a period of about four to six hours.

我不能说这种状态最舒服，尽管我并没有感到心跳加速或类似症状。

I can't say it was the most comfortable state, although I did not feel as if I had racing heart or anything of that sort.

在那整个期间，我基本上感觉自己处于一种狭窄的注意力隧道中。

I basically felt as if I was in a narrow tunnel of attention for that entire period.

我对这次体验不满意的方面是，很难从这种状态中平复下来。

One thing I did not like about the experience is that it was a very hard experience to come down from.

虽然没有出现崩溃，但我发现这种高度兴奋的状态持续了数小时才逐渐消退；尽管最强烈的状态只持续了四小时，但八到十二小时后，我仍然感觉像是每四分钟才眨一次眼。

There was no crash, but I found that that high arousal state didn't taper off for many hours later, even though it was most heightened for four hours, I would say anywhere from eight to twelve hours later, I still felt like I was blinking once every four minutes or so.

我当然曾被这个播客以及其他场合的人指责过眨眼次数太少。

And I've certainly been accused on this podcast and at other times of blinking too seldom.

据我所知，我没有注意力缺陷多动障碍（ADHD）。

To my knowledge, I don't have ADHD.

我从未被开具过治疗ADHD的药物。

I've never been prescribed ADHD meds.

我从未接受过ADHD的检测。

I've never been tested for ADHD.

我认为我没有ADHD，但服用阿莫达非尼确实提升了我的注意力水平；不过，仅凭这一次经历，我并不想再重复了。

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.

我绝对不希望在那种状态下学习新知识。

I certainly would not want to be in that state for learning new material.

当我坐下来研究播客、实验室论文，或搜索信息、向他人、书籍、讲座或播客学习时。

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.

我希望处于一种警觉但平静的状态，能够深入思考各种观点，并用手写的方式整理思路。

I want to be in a state of alertness, but calm where I can really consider the ideas, I can script things out by hand.

我坚信通过手写来记录内容有助于日后回忆，还会画一些简单的示意图。

I'm a big believer in writing things out by hand to remember them later, drawing little diagrams.

我绝不希望为了学习而处于那种极低剂量的赖莫达非尼所引发的状态。

I would not want to be in the state that even that very low dose of R Modafinil put me in, in order to learn.

我应该提一下，莫达非尼和赖莫达非尼如果与你的身体不兼容，或剂量过高，可能会引发诸多副作用，比如食欲下降、流鼻涕、头痛，还可能出现皮疹。

And I should mention that both Modafinil and R Modafinil 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, people can get a runny nose, headache, there's this instance of skin rashes.

事实上，莫达非尼和赖莫达非尼没有更广泛处方的原因之一，是曾出现一种极为罕见的皮肤状况：某些服用过特定药物（不仅限于莫达非尼或赖莫达非尼）的人出现了严重的烧灼样水疱。

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 modafinil have developed these very severe burn type blisters.

在某些情况下，这种状况可能是致命的。

And in some cases this can be fatal.

这再次说明，这种现象极为罕见，至少有一名患者在参与莫达非尼治疗注意力缺陷多动障碍（ADHD）的临床试验时出现了这种状况，称为史蒂文斯-约翰逊综合征。

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, it's called Stevens Johnson syndrome.

如果你对皮肤擦伤、病变等图像感到不适，请不要在互联网上搜索相关内容，除非你能够承受——或许根本就不要看。但重点是，莫达非尼和赖莫达非尼之所以未被广泛用于ADHD治疗，且仍属超说明书用药，正是因为史蒂文斯-约翰逊综合征被列为潜在风险。不过，我所接触的ADHD专家对此感到有些沮丧，因为他们坚持认为，在这项试验中，服用莫达非尼的患者出现这种可能导致致命皮疹的综合征的频率，并不高于其他已获批药物。

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, 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, although the ADHD specialists that I spoke to are somewhat frustrated with that because they insist that the frequency of this syndrome that causes the 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.

这就牵涉到药物获批标准的诸多问题：哪些药物能获批，哪些不能。

So this gets into all sorts of issues around what drugs make it to approval and which ones don't.

正如我们所知，莫达非尼和赖莫达非尼已经在普通人群中被用于其他用途。

And as we know, modafinil and armodafinil are already being prescribed in the general population for other things.

这专门讨论了是否应该为患有多动症的儿童开具处方的问题。

This was dealing specifically with the question of whether or not it should be prescribed in kids with ADHD.

当然，我认为在考虑哪些药物应被批准用于治疗任何人时，尤其是儿童时，必须极其谨慎。

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.

为了全面讨论用于治疗多动症的药物，我们将其分为典型类和非典型类，典型类包括阿得拉尔、Vyvanse、哌甲酯等药物。

And to round out our discussion of drugs used for the treatment of ADHD that fall into, let's call it the atypical category, the typical category being Adderall, Vyvanse, methylphenidate, and things of that variety.

非典型类则包括莫达非尼、阿莫达非尼、普罗吡仑、安非他酮等。

The less typical would be modafinil, armodafinil, proprion, Wellbutrin, and so forth.

这一非典型类别中的最后一种是可乐定。

The last in this category of atypical is guanfacine.

可乐定是一种有趣的化合物。

Guanfacine is an interesting compound.

它最初是为降低血压而开发的，确实能降低血压，并且是一种α-2A受体激动剂，α-2A是去甲肾上腺素的受体。

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.

因此，可乐定是一种非兴奋剂类药物，用于治疗多动症，同时也用于治疗其他一些仅作用于去甲肾上腺素系统的疾病。

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.

它并不作用于多巴胺系统。

It is not tapping into the dopamine system.

但我们之前讨论的其他药物都会显著提升多巴胺和去甲肾上腺素水平。

But all the other stuff that we talked about is really ramping up dopamine and norepinephrine.

胍法辛仅增加去甲肾上腺素，其机制是通过激活或刺激去甲肾上腺素系统中的特定部分——即α-2A受体。

Guamfacine 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.

胍法辛的有趣之处在于，它激活了多条通路，这些通路会反馈至自主神经系统，从而抑制交感神经系统的激活。

What's interesting about guamfacine 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.

因此，与今天我们讨论的大多数药物不同，那些药物属于交感神经兴奋剂，通常会让人更加兴奋、警觉和亢奋。

So whereas most of what we talked about today are sympathomimetics, they tend to make us more ramped up, more aroused and alert.

而胍法辛的作用恰恰相反。

Guamfacine is doing the opposite.

因此，它并不常被处方，因为许多人在服用胍法辛后，要么对ADHD症状没有效果，要么会感到非常嗜睡。

And as a consequence, it's not prescribed that often because a lot of times when people take guamfacine, it either has no effect on ADHD symptoms, or it tends to make people feel very sleepy.

然而，有一小部分人群——大约5%到10%尝试过该药的人，包括儿童——确实获得了ADHD症状的显著缓解，并且他们对胍法辛的耐受性优于我们迄今为止讨论的其他药物。

However, there's a small subset of individuals, probably about five to ten percent 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.

胍法辛的作用方式也非常有趣。

The way guanfacine works is also really interesting.

你现在熟悉了蓝斑，这是大脑后部的一群神经元，我们称之为核团，它们会向大脑其他部位释放去甲肾上腺素，而这些部位正是胍法辛作用并刺激的α-2A受体，它们涉及大脑中多个与增强我们所见和需要关注的刺激显著性和相关性的区域。

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.

看起来，胍法辛能够以高于正常基线的方式激活前额叶皮层网络，这是有益的。

It appears that guamfacine can activate the prefrontal cortical networks in ways that are above their normal baseline, so that's good.

因此，它能改善执行功能——我们之前提到的类似管弦乐队指挥或教师那样的功能，并增强蓝斑输出的效率。

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.

这似乎能增加蓝斑神经元与前额叶皮层之间的协调放电。

And what that seems to do is increase the coordinated firing of locus coeruleus neurons with prefrontal cortex.

在许多方面，它就像在精细调节管弦乐队指挥的运作，这种调节在儿童时期对教会大脑回路如何专注于一件事并忽略其他所有事物至关重要。

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，这也是胍法辛如今不仅被批准用于成人ADHD治疗，更主要应用于6至17岁儿童ADHD治疗的原因——希望这些孩子服用药物后，相关脑回路能学会如何集中注意力、关注特定事物，并减少冲动和多动，最终可能停药。

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, 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.

不过，有时人们仍需长期持续服药。

Although sometimes again, people have to stay on them indefinitely.

关于胍法辛的另一点是，由于它能降低血压并具有抑制整体交感神经兴奋的作用，因此有时会与其他多动症药物联合使用。

The other thing about guamfacine 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.

所以，确实有一些儿童和成人正在服用阿得拉尔和胍法辛，或者服用维万斯和胍法辛，这就开始涉及药物组合以及其他一些让人略感不安的问题，因为用一种药物来减轻另一种药物的副作用、进行补偿和调节，这已经接近所谓的多药理学了。

So yes, there are kids out there and adults out there who are taking Adderall and Guamfacine, or they're taking Vyvanse and Guamfacine, 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, you know, is getting towards what's called poly pharmacology.

而且，我认为人们对此感到担忧是可以理解的。

And, you know, I think it's understandable that people be concerned about that.

然而，再次与一些多动症专家讨论后，似乎确实存在一类儿童和成人，他们对标准的多动症药物反应不佳，而对这些个体而言，胍法辛提供了相当程度的显著缓解。

And yet, again, in reviewing 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.

关于胍法辛，我绝不会鼓励任何未被处方的人服用它，但如果你认识有人在未经批准的情况下使用胍法辛来提高专注力或增强其生理或心理状态，请告知他们：胍法辛会显著降低对酒精的耐受性，即使少量饮酒也可能导致严重问题，甚至可能致死。

One note about guanfacine, in no way, shape or form am I encouraging anyone who's not prescribed guanfacine to take it, 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 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.

因此，这是关于胍法辛的一个非常严重的警告。

So that's a very serious warning with guanfacine.

今天，我们讨论了多种用于治疗多动症的化合物，现在应该清楚这些药物的共同主题了。

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.

总体主题是，它们通常会提高整体的觉醒和警觉水平，从而降低多动、冲动和注意力不集中的程度。

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.

乍一看，这似乎违反直觉：提高觉醒水平却能减少多动和冲动，但事实确实如此，因为这些药物通过作用于多巴胺和去甲肾上腺素等神经调质系统，能够促进神经可塑性。

And on the face of it, that might seem counterintuitive, raise arousal to reduce hyperactivity and impulsivity, indeed that's the case because these compounds, because they act on neuromodulator systems like dopamine and norepinephrine are effective in creating neuroplasticity.

它们改变大脑神经回路中连接的强度，从而促成更专注、更少冲动和更少多动的状态。

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.

因此，我们讨论了不同 ADHD 药物实现这一效果的各种机制，包括常见的如哌甲酯、阿得拉尔和维万斯，以及一些新增的非典型药物，如莫达非尼、阿莫达非尼、胍法辛和安非他酮。

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.

在可能的情况下，我试图强调这些不同药物的短期和长期效应。

And where possible, I tried to highlight both the short and long term effects of these various compounds.

我也试图回应一些关于这些药物的主要担忧，尤其是为什么我们要让这么多孩子服用安非他明，以及长期使用会带来什么后果？

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?

在今天的节目中，我努力强调了这些药物的即时和长期益处，同时也指出了它们可能带来的即时和长期风险。

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.

当然，未经处方而滥用这些药物存在真正的成瘾和滥用风险，甚至可能导致精神病发作，同时对于患有多动症的人群长期使用这些药物也存在相应风险。

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.

然而，不治疗多动症的症状同样会带来显著的风险。

And yet it is also clear that not treating the symptoms of ADHD carry significant risk as well.

科学和临床文献非常明确地表明，这一点在关于ADHD的那期节目中也有详细阐述，你可以在hubermanlab.com找到该节目：药物治疗与行为干预的结合似乎优于单独使用药物治疗或行为干预。

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.

这凸显了在治疗ADHD时结合多种方法的重要性，以及与真正了解ADHD并紧跟最新科学和临床文献的认证精神科医生合作的必要性。

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.

如果你正在学习或享受这个播客，请订阅我们的YouTube频道。

If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel.

这是一种绝佳的零成本支持方式。

That's a terrific zero cost way to support us.

此外，请在Spotify和Apple上订阅本播客。

In addition, please subscribe to the podcast on both Spotify and Apple.

在Spotify和Apple上，你还可以为我们留下最多五颗星的评价。

And on both Spotify and Apple, you can also leave us up to a five star review.

也请查看节目开头和过程中提到的赞助商。

Please also check out the sponsors mentioned at the beginning and throughout today's episode.

如果你有任何问题、对播客的评论，或希望我邀请的嘉宾建议，请在YouTube的评论区留言。

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.

评论。

Comments.

虽然今天这一集不太涉及，但在许多往期的《休伯曼实验室》播客中，我们讨论过补充剂。

Not so much on today's episode, but on many previous episodes of the Huberman Lab Podcast, we discuss supplements.

虽然补充剂并非每个人都需要，但许多人通过它们在改善睡眠、激素支持以及专注力等方面获得了显著益处。

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.

《休伯曼实验室》播客很荣幸与Momentous补充剂合作。

The Huberman Lab Podcast is proud to have partnered with Momentous supplements.

如果你想查看《休伯曼实验室》播客中提到的补充剂，可以访问 LivMomentous（拼写为 o u s）。

If you'd like to see the supplements discussed on the Huberman Lab Podcast, you can go to LivMomentous spelled o u s.

网址是 livmomentous.com/huberman。

So it's livmomentous.com/huberman.

如果你还没有在社交媒体上关注我，我在所有平台上的账号都是“Huberman Lab”，包括 Facebook、LinkedIn、Twitter 和 Instagram。

If you're not already following me on social media, I am Huberman Lab on all platforms, so that's Facebook, LinkedIn, Twitter, and Instagram.

在所有这些平台上，我会分享科学及相关工具的内容，其中一部分与《休伯曼实验室》播客的内容重叠，但大部分内容是播客之外的独特内容。

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.

所以，再次提醒，我在所有社交媒体平台上的账号都是Huberman Lab。

So again, it's Huberman Lab on all social media platforms.

如果你还没有订阅我们的《神经网络通讯》，《神经网络通讯》是一份月度通讯，我们会提炼出特定播客的核心要点，并列出各种工具包，比如睡眠工具包、神经可塑性工具包、多巴胺优化工具包等等，所有内容完全免费。

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, all of which is available at zero cost.

你只需访问hubermanlab.com，进入菜单，向下滚动到通讯栏目，输入你的邮箱即可。

You simply go to hubermanlab.com, go to the menu, scroll down to newsletter and supply your email.

我们不会与任何人分享你的邮箱信息。

We do not share your email with anybody.

感谢你参加今天关于治疗ADHD的药物干预措施的讨论。

Thank you for joining me for today's discussion, all about pharmaceutical interventions for the treatment of ADHD.

最后但同样重要的是，感谢你对科学的关注。

And last but certainly not least, thank you for your interest in science.