Huberman Unveils Neurochemical Toolkit to Control Focus and Energy

休伯曼公布掌控专注与精力的神经化学工具箱 将每日日照、冷暴露及前体补充剂与自然昼夜节律相结合，可优化多巴胺、肾上腺素、乙酰胆碱和血清素水平，以实现巅峰认知表现。 Andrew Huberman 深入解析了多巴胺、肾上腺素、乙酰胆碱和血清素这四种关键神经调控物质，如何在一天中的三个主要阶段塑造日常脑功能。他概述了清晨接受日照和刻意冷暴露等基础行为习惯，以及安全调节神经化学水平的具体营养与补充剂方案。通过运用这些工具，个人可以根据自身特定目标来调控大脑化学状态，从而提升专注力、驱动力、放松感与整体健康水平。 人体在醒后遵循三个生理阶段：阶段 1（0-9 小时）由高水平多巴胺与肾上腺素主导，阶段 2 转向血清素主导以促进放松，阶段 3 进入深度睡眠，而驱动专注与神经可塑性的乙酰胆碱则完全按需释放。 (0:27) 醒后尽早接受清晨阳光照射可直接上调多巴胺受体表达，配合摄入 100 至 250 毫克咖啡因能提高 D2 与 D3 受体密度及敏感性，从基线层面显著提升动机与警觉度。 (8:58) 刻意冷暴露能促使多巴胺和肾上腺素大幅平稳升高并维持数小时且无断崖式跌落，而清晨强制身体运动或进行约 25 次循环过度换气呼吸法，能刺激脑内蓝斑核即刻释放肾上腺素以驱散脑雾。 (15:16) 认知专注度可通过蛋黄、大豆等富含胆碱的食物或 Alpha-GPC 促进乙酰胆碱合成来提升；而接收感恩、身体接触及摄入肌醇则有助于调节血清素通路，增强满足感并改善深度睡眠。 (24:40)

Stanford neurobiology professor Andrew Huberman outlines how human mental states and physical performance are governed by four primary neuromodulators—dopamine, epinephrine, acetylcholine, and serotonin—which can be systematically modulated through circadian-aligned behaviors, nutrition, and targeted supplementation. Circadian Rhythms Govern Daily Neuromodulator Baselines (0:27) Huberman explains that human biology follows a 24-hour cycle segmented into three distinct phases relative to waking. Phase 1 (0 to ~9 hours post-waking) is dominated by elevated baseline dopamine and epinephrine, representing the daily peak for drive and alertness. In Phase 2 (9 to ~16 hours), dopamine and epinephrine taper off while serotonin levels rise to favor relaxation and satiety. Phase 3 (17 to 24 hours) is reserved for deep, restorative sleep. Steroid hormones also modulate these baselines: testosterone aligns with dopamine, cortisol tracks with epinephrine, and oxytocin and prolactin pair with serotonin. Unlike the other neuromodulators, acetylcholine operates without a rigid circadian rhythm. Released locally at nerve-to-muscle synapses and across cortical circuits, it acts on demand to sharpen sensory focus and facilitate neuroplasticity during learning and motor tasks. Behavioral and Supplemental Protocols for Dopamine (8:58) To enhance baseline drive, Huberman advises establishing behavioral habits before turning to supplements. Early-morning sunlight exposure outdoors within 1 to 3 hours of waking triggers retinal pathways that upregulate D2 and D3 dopamine receptor expression. Ingestion of 100 mg to 250 mg of caffeine similarly enhances receptor sensitivity while blocking adenosine receptors. For a sustained, multi-hour elevation in baseline dopamine without a crash, deliberate cold water immersion serves as a potent behavioral protocol, particularly when performed during Phase 1. For acute boosts, L-tyrosine (100 mg to 2,000 mg) and phenethylamine (PEA, 300 to 600 mg) elevate dopamine for short intervals, though individual sensitivity varies and crashes can occur. Huberman explicitly warns against using Mucuna pruriens due to severe post-use crashes, and urges caution regarding mood disorders and psychiatric medications. Activating Epinephrine for Energy and Alertness (18:00) Epinephrine (adrenaline) fuels physical vigor, mental alertness, and the drive to move. Because adrenal epinephrine cannot cross the blood-brain barrier, central nervous system alertness relies on the locus coeruleus, a cluster of brainstem neurons that distributes epinephrine throughout neural circuits. Physical movement immediately stimulates this pathway, resolving morning sluggishness through a bidirectional feedback loop between body activity and brain arousal. Beyond exercise and cold water immersion, deliberate cyclic hyperventilation—roughly 25 cycles of deep, rapid inhales followed by passive or active exhales—surges adrenaline and raises body temperature. However, Huberman cautions that individuals prone to panic attacks or high anxiety should avoid or approach hyperventilation practices carefully, as the rapid physiological arousal can trigger intense agitation. Optimizing Acetylcholine for Cognitive Focus (22:25) Acetylcholine directs attentional focus and memory encoding across both high-arousal and calm tasks. Sustaining baseline acetylcholine synthesis requires adequate dietary choline, obtained through whole foods such as egg yolks, liver, beef, chicken, fish, soybeans, and mushrooms. For acute, high-focus work sessions lasting 1 to 4 hours, Huberman evaluates targeted nootropic compounds. While acknowledging nicotine's affinity for acetylcholine receptors, he warns strongly against vaping and smoking due to cancer risks and addiction potential. Instead, he discusses using 300 mg of Alpha-GPC prior to intensive work or exercise 3 to 4 times per week to increase choline availability, occasionally paired with Huperzine A to inhibit acetylcholinesterase from breaking down active acetylcholine. Cultivating Serotonin for Contentment and Rest (25:34) Serotonin produces feelings of calm, contentment, and the perception of having sufficient internal resources, contrasting with the outward pursuit driven by dopamine. While pharmaceutical SSRIs increase serotonin clinically, behavioral practices can naturally support serotonergic tone. Psychological research indicates that receiving gratitude—and particularly observing gratitude exchanges between others—activates serotonergic pathways far more effectively than actively expressing gratitude. Physical touch, such as hugs and holding hands, also elevates serotonin. At the biochemical level, dietary tryptophan provides the essential precursor for serotonin production. For evening rest and deep sleep, Huberman notes personal success taking 900 mg of myo-inositol every third night, though he stresses that nutritional compounds should never replace prescribed medications without professional medical guidance. Huberman concludes that optimizing brain function does not rely on a single intervention, but on establishing foundational daily habits aligned with natural circadian shifts. Behavioral tools should be layered contextually based on sleep quality, travel, and daily demands, while pharmacological and supplemental aids require careful individual titration and medical oversight.

斯坦福大学神经生物学教授 Andrew Huberman 指出，通过掌握多巴胺、肾上腺素、乙酰胆碱和五羟色胺这四种核心神经调质的基线与急性波动规律，人们可以借助光照、体温、呼吸、饮食及靶向补充剂等工具，主动调控专注力、动机与身心状态。 昼夜节律与神经调质的三阶段模型 (0:27) 人体神经系统在24小时周期内呈现结构化波动。Huberman 提出了以清醒时间为起点的三阶段生物学模型：第1阶段（醒后0至约9小时）由高基线的多巴胺与肾上腺素主导，是体能、警觉与目标追求的天然峰值期；第2阶段（醒后约9至16小时）多巴胺和肾上腺素渐次回落，五羟色胺水平上升，机体转向放松与安宁；第3阶段（醒后17至24小时）则对应深度睡眠与神经修复。不同于呈现严格昼夜节律波动的上述调质，乙酰胆碱主要根据具体的认知专注与学习任务按需即时释放。 此外，激素系统与神经调质存在显著协同。睾酮通常能增强多巴胺合成与行为驱动力；皮质酮（如皮质醇）与肾上腺素紧密追踪，共同维持清醒与警觉基线；催产素和催乳素配合五羟色胺，促进社交联结与安适体验；乙酰胆碱则相对独立于主要类固醇激素，直接控制神经肌肉接头的物理收缩和局部突触可塑性。 多巴胺调控：建立长期动力与急性激发 (8:58) 优化多巴胺系统的首要任务是提高受体表达与敏锐度，而非单纯制造急剧峰值。Huberman 强调，醒后早晨（最理想在1小时内，至多3小时内）走出户外接受阳光直射，可通过视网膜信号通路上调 D2 与 D3 多巴胺受体密度，从而筑牢日常动机基线。适量摄入咖啡因（约100至250毫克）既能阻断腺苷受体消除困倦，又能增强 D2/D3 受体对体内多巴胺的敏感性。刻意进行冷水暴露（冷水淋浴或冰水浸泡）能促使去甲肾上腺素与多巴胺实现长达数小时的平稳持续上升，且不引发崩溃反弹；在第1阶段实施该方案效果最为显著。 对于短时间内急需提升动力的场景，可选择性使用膳食补充剂。L-酪氨酸（100至2000毫克）能在摄入后15至45分钟内显著提升多巴胺并维持半小时至2小时，但停药时可能伴随能量下降；苯乙胺（PEA，300至600毫克）亦可迅速提升积极情绪与清晰度。对于含约99%左旋多巴的刺毛黧豆，Huberman 明确不建议常规使用，因其剧烈峰值后往往紧伴严重的低谷反弹。 肾上腺素驱动：摆脱脑雾与快速警觉 (18:00) 肾上腺素是驱动体能警觉与行动倾向的核心介质。生理上，外周肾上腺分泌的肾上腺素无法跨越血脑屏障，中枢神经系统的唤醒完全依赖脑干蓝斑核（Locus Coeruleus）向全脑神经网络释放肾上腺素。Huberman 指出，在清晨大脑处于迟滞与脑雾状态时，强迫身体展开运动能形成双向正反馈：肢体活动刺激蓝斑核分泌肾上腺素，进而唤醒中枢神经系统以驱动更多行动。 呼吸控制是快速拉升肾上腺素的即时行为工具。进行循环式过度通气（Cyclic Hyperventilation，连续约25次深度快速吸气与呼气循环）能瞬间释放肾上腺素，快速提高体温与神经兴奋度。Wim Hof 呼吸与 Tummo 呼吸均基于此原理。Huberman 警示，该呼吸法会诱发急性生理应激与烦躁感，易焦虑或有惊恐障碍者应谨慎或避免使用。 乙酰胆碱与专注力：饮食前体与补充剂 (22:25) 乙酰胆碱负责主导大脑注意力的聚光灯与记忆编码，既支持高唤醒的竞技与高压工作，也能维持低唤醒的深度阅读与思考。维持充足的乙酰胆碱储备需从饮食中摄入足量胆碱，富含胆碱的食物包括全蛋（尤其是蛋黄）、牛肉、鸡肉、鱼类、动物肝脏以及大豆和蘑菇等。 在需要进行1至4小时深度工作或训练时，可借助针对性补充剂强化乙酰胆碱传导。Huberman 个人会在高强度工作或训练前补充 300 毫克 Alpha-GPC 以增加胆碱供应；石杉碱甲（Huperzine A）则通过抑制乙酰胆碱酯酶延缓其降解。尽管尼古丁可强效激活烟碱型受体，但鉴于吸烟与电子烟的高致瘾性及致癌风险，Huberman 强烈反对吸烟，仅提及个别人群会谨慎尝试尼古丁口香糖。 五羟色胺系统：心理机制与深度睡眠 (25:34) 五羟色胺负责带来安宁、满足与饱腹感，向大脑传递“当前拥有的已经足够”的心理信号。肢体拥抱与牵手等温和的身体接触能直接提升五羟色胺水平。在心理神经机制上，心理学证据表明，接受他人的诚挚感谢，或是作为旁观者观察他人给予与接受感恩，在激活五羟色胺通路上远比单纯主动向他人表达感谢更为强烈。 在生化层面，色氨酸是合成五羟色胺的关键氨基酸前体。为了改善夜间放松与睡眠深度，Huberman 分享了自己每隔数天补充 900 毫克肌醇（Myo-Inositol）的经验。但他同时提醒，过高的五羟色胺会导致食欲钝化与嗜睡倦怠，且任何营养补充剂均不能未经医嘱擅自替代处方精神类药物。 Huberman 强调，调控大脑化学物质的核心在于建立个性化且富有弹性的“工具箱”，而非寻找某种单一的灵丹妙药。最佳路径是先以光照、运动和昼夜作息夯实神经调质的稳态基线，再根据旅行、压力或任务需要，在特定场景下合理搭配行为动作与安全性受试过的补充剂，使神经生物学状态精准服务于当下的生活目标。

[2:27] Andrew Huberman: Acetylcholine is used at the nerve-to-muscle synapse... neurons don't just control other neurons electrically. The way you are able to move in fact is because neurons are controlling the electric activity of muscles, literally the contraction of muscle fibers, and that control is exerted through the release of acetylcholine. [12:12] Andrew Huberman: My particular protocol, the one I use is I'll take phenethylamine at dosages of about 300 to 600 milligrams along with some L-tyrosine or I'll take it on its own with a molecule... alpha-GPC. [25:34] Andrew Huberman: Receiving, much more than giving gratitude, is what activates those serotonin pathways... Observing others giving and receiving gratitude is immensely powerful for evoking serotonin and the activity of serotonergic circuits in you, the observer.

[0:00] Welcome to Huberman Lab Essentials, [0:01] [music] where we revisit past episodes [0:04] for the most potent and actionable [0:06] science-based tools for mental health, [0:08] physical health, and performance. [0:11] I'm Andrew Huberman, and I'm a professor [0:13] of neurobiology and opthalmology at [0:16] Stanford School of Medicine. Today we [0:18] are going to discuss your brain [0:19] chemistry and how to control and [0:21] optimize your brain chemistry for all [0:24] aspects of mental health, physical [0:25] health, and performance. The important [0:27] thing to know is that your brain and [0:29] your spinal cord and the rest of your [0:32] so-called nervous system control all the [0:35] organs of your body and that all the [0:37] organs of your body feed back, meaning [0:40] they communicate through chemicals and [0:41] other means to your nervous system. And [0:44] vitally important is the fact that which [0:47] neural circuits are active and which [0:50] neural circuits are likely to be less [0:53] active at any given moment depends on [0:56] two major categories of chemicals. It [0:59] depends on hormones and it depends on [1:02] so-called neurom modulators. And the [1:05] four neurom modulators that we're going [1:06] to talk about today that are of the [1:08] utmost importance for your goals are [1:12] dopamine, epinephrine, also called [1:14] adrenaline, serotonin and acetylcholine. [1:18] There are many features of how neurom [1:20] modulators work but for sake of today's [1:22] discussion we only need to focus on two [1:25] of those features and those are fast [1:27] acting features and longer slower [1:30] features or what we call baseline [1:32] features. Now perhaps surprisingly I'd [1:34] like to focus on the slow actions of the [1:36] neurom modulators first because those [1:38] slow actions of the neurom modulators [1:40] are happening in you and in me and in [1:43] everyone right now and they set the [1:45] backdrop the context in which the [1:48] various tools to manipulate dopamine, [1:50] epinephrine, serotonin or acetylcholine [1:53] will work. What do I mean by the context [1:56] or the backdrop or the baseline? Well, [1:59] it's fair to say that most people are [2:02] awake during the daytime and asleep at [2:04] night. So schedules of sleep and [2:06] wakefulness will vary, but in general, [2:08] everybody, regardless of whether or not [2:10] you're nocturnal or you're so-called [2:12] dal, you're awake during the day, pretty [2:14] much everybody follows a schedule in [2:16] which from 0 to 9 hours after waking, [2:21] that is from the time you wake up until [2:23] about 9 hours later, the neurom [2:26] modulators dopamine and epinephrine tend [2:30] to be at their highest levels that they [2:32] will be at any point in the 24-hour [2:36] period in any period of the day. So, we [2:39] can call this 0 to 9h hour period phase [2:42] one of the day just for simplicity. And [2:44] I've referred to this before in a [2:46] previous episode, but not in this exact [2:49] context. From 9 to about 16 hours is [2:51] what we will call phase 2. And that's [2:54] when dopamine and epinephrine levels [2:56] tend to subside a bit compared to the [2:59] earlier phase one part of the day. and [3:02] serotonin levels start to increase. And [3:05] then phase three of the 24-hour cycle, [3:08] which is from about and again about [3:10] these are approximates from about 17 [3:12] hours after waking until about 24 hours [3:15] after waking is phase three of the day. [3:18] We're not going to focus too much on [3:20] phase three today because phase three of [3:24] the 24-hour cycle, that 17 to 24h hour [3:26] period, is one in which you ought to be [3:28] deeply asleep whether or not you're [3:29] nocturnal or dial. So, we're mainly [3:31] going to focus on what we're calling [3:34] phase one and phase two. Phase one being [3:36] this dopamine epinephrine dominated [3:38] phase of our day and phase two being [3:40] this more serotonin or serotonin [3:43] dominated portion of the day. And then [3:45] you might say, well, what about [3:46] acetylcholine? [3:48] You forgot about acetyloline. Well, we [3:49] didn't forget about acetyloline. [3:50] Acetylcholine is under control more in [3:54] terms of what we happen to be doing at [3:57] any given moment. whether or not we're [3:58] focusing or not focusing, whether or not [4:00] we're learning or not learning. And here [4:02] I'm referring to acetylcholine [4:04] specifically in the context of the brain [4:05] and thinking because as some of you are [4:08] probably shouting out there, right? If [4:10] you're exercise physiologists or you [4:12] know anything about how the brain [4:13] controls movement, acetylcholine is used [4:16] at the nerve to muscle synapse, right? [4:19] So neurons don't just control other [4:21] neurons electrically. The way you are [4:23] able to move in fact is because neurons [4:24] are controlling the electric activity of [4:27] muscles literally the contraction of [4:29] muscle fibers and that control is [4:32] exerted through the release of [4:34] acetyloline. So acetyloline is working [4:36] at muscles as well but we're not focused [4:37] on that today. We're focused on what we [4:40] can do during phase one of the day and [4:43] what we can do during phase two of the [4:44] day to control the specific [4:47] neuromodulators dopamine, epinephrine, [4:49] serotonin, and acetylcholine toward [4:51] particular end goals. So again, it's [4:54] really important to understand what the [4:57] backdrop of these neurom modulators is, [4:59] the so-called baseline, and that they [5:02] vary across the day if you are going to [5:04] be able to leverage tools to optimize [5:06] your brain chemistry. Before we dive [5:08] into the more pointed directed effects [5:10] of specific tools on neurom modulators, [5:13] I'd like to just briefly mention [5:15] hormones because they are also important [5:17] for understanding the background and the [5:20] context and these baseline levels of [5:22] neurom modulators. Hormones have many [5:25] different effects on the brain and body [5:28] and not unlike neurom modulators, some [5:30] of those effects are very fast, some of [5:32] them are very slow. Today we want to [5:33] think about hormones as they relate to [5:35] these neurom modulators. the dopamine, [5:37] serotonin, epinephrine, and [5:39] acetylcholine. And in general, [5:42] testosterone tends to collaborate with [5:45] and increase the action of dopamine. [5:48] That's not always the case, but in [5:49] general, when testosterone goes up, [5:52] dopamine goes up. In general, when [5:56] corticosterones like cortisol and some [5:59] related steroid hormones increase, [6:01] epinephrine levels go up. And in [6:04] general, when hormones like oxytocin or [6:07] prolactin are increased, levels of [6:10] serotonin go up. And then we have poor [6:13] old lonely acetylcholine off on its own. [6:15] But it's not poor and lonely. It [6:16] actually has incredibly potent effects [6:18] on its own. So it's really that it just [6:19] doesn't need much help from the hormone [6:22] systems or at least not the steroid [6:24] hormone systems in order to have its [6:25] tremendous effects. If you understand [6:28] these four neurom modulators and you [6:30] understand that while there are many [6:32] tools ranging from pharmarmacologic to [6:34] behavioral that can tap into these [6:35] neurom modulator systems that kind of [6:38] dopamine pull back on serotonin and so [6:40] on. Well then you can create a sort of [6:44] kit a grabag of things that you can use [6:47] in any context or I should say that you [6:50] can look to depending on the context [6:52] you're in and create the states of body [6:54] and mind that you want. Now once again [6:56] painting with a somewhat broad brush but [6:59] nonetheless an accurate brush we can say [7:02] that dopamine when elevated above [7:05] baseline [7:07] tends to increase states of motivation [7:10] both mental and physical motivation [7:13] drive and to some extent focus. [7:16] epinephrine and a closely related [7:19] molecule called norepinephrine. [7:22] And again, I want to emphasize that [7:23] epinephrine is adrenaline and adrenaline [7:26] is epinephrine. Norepinephrine is [7:28] noradrenaline and noradrenaline is [7:31] norepinephrine. But today, we're going [7:32] to just simply talk about epinephrine [7:34] and norepinephrine. [7:36] That category of neurom modulator is [7:39] mainly responsible for generating our [7:42] energy, our level of fuel and baseline [7:46] level of forward center of mass as I [7:49] like to call it. When epinephrine levels [7:51] are high, we tend to feel agitated. We [7:53] tend to feel like we want to move. We [7:55] tend to feel like we can't shut down our [7:57] thinking and our anticipation of what's [7:59] going to happen next. And when [8:00] epinephrine levels are very, very low, [8:02] we actually have less physical energy. [8:04] we tend to have less mental energy in [8:07] terms of generating thoughts very [8:09] quickly and so on and so forth. Now the [8:11] neurom modulator serotonin [8:13] creates a number of different states in [8:15] the brain and body but for sake of [8:18] today's discussion we're going to think [8:19] about the predominant states that it [8:21] creates and those are states of [8:23] contentness being happy feeling fairly [8:26] relaxed feeling soothed and to some [8:29] extent even some relief from pain or [8:32] lack of pain. Serotonin is associated [8:36] with a feeling of satiety, of having [8:38] enough of what we already have. And [8:41] acetylcholine, we can say, is mainly [8:45] associated with states of focus. And we [8:49] can go a step further and say that it's [8:50] mainly associated with steps of focus as [8:53] they relate to learning and encoding new [8:55] information, so-called neuroplasticity. [8:58] So let's say you want to be more [8:59] motivated. You want to be more in [9:01] pursuit of goals and you want to have [9:03] more energy and to be more focused. [9:05] There are many ways to go about that. In [9:07] fact, there's a near infinite cloud of [9:10] opportunities. Everything from [9:12] prescription drugs to elicit drugs, [9:14] which I certainly do not recommend. [9:16] Supplements, nutrition, you can listen [9:19] to particular music. You can do all [9:21] sorts of cognitive, behavioral, [9:23] nutritional supplementation tricks. or [9:26] you can just understand that what you're [9:29] really after are increases in dopamine [9:31] above baseline that you control and [9:35] there are ways to control them that are [9:36] quite potent and science tells us which [9:40] tools are going to be the most potent [9:42] and the most versatile for you. So, I'm [9:45] going to share those tools with you now [9:46] with the caveat that each one of those [9:49] tools could be its own entire podcast [9:52] episode and that we've done near entire [9:54] episodes on each of these tools or small [9:57] collections of these tools. So, I'm [9:58] going to cover these in somewhat [9:59] superficial manner. Let's say you want [10:01] to increase dopamine for sake of [10:02] increasing motivation. [10:05] The first thing to do is to understand [10:07] what the natural behavioral tools are [10:09] for increasing dopamine and to do those [10:11] as consistently as possible. Again, [10:14] these are tools that you'll want to do [10:15] nearly every day, if not every day. And [10:19] I know I'm sounding like a broken record [10:21] on this one, but here again, we come to [10:24] sunlight. And I should say, not just the [10:28] desire to, but really the need for [10:31] viewing the maximum amount of sunlight [10:33] that one can reasonably get given [10:35] schedules and locations in the world, [10:37] time of year, etc. in the early part of [10:39] the day. [10:41] Within the first hour of waking ideally, [10:44] but certainly in the first 3 hours of [10:46] your day, you going to want to maximize [10:48] sunlight exposure to your eyes. Never [10:50] look at the sun or any other light so [10:52] bright that it's painful to look at. And [10:54] yes, of course, blinking is fine, but [10:55] no, take sunglasses off, go outside once [10:57] the sun is out, and get some natural [10:59] light in your eyes. So if you get [11:00] sunlight exposure to your eyes and it [11:02] does have to be to your eyes in the [11:03] early part of the day, you increase the [11:05] amount of dopamine receptor that you [11:06] have which allows whatever circulating [11:08] dopamine happens to be there to have a [11:10] greater effect on motivation and I [11:13] should say also on mood and feelings of [11:15] being in pursuit and generally in [11:18] craving and pursuit of things in life. [11:20] Now there's another way to increase the [11:22] effect of whatever dopamine happens to [11:24] be circulating in your brain and body [11:27] and this again relates to increasing the [11:29] number or the efficacy of the receptors [11:32] for dopamine. How do you do that? Well, [11:35] turns out that regular ingestion of [11:37] caffeine at safe and appropriate levels [11:40] of about 100 to 250 milligrams is going [11:44] to increase the number of D2 and D3 [11:46] dopamine receptors. When you drink [11:47] caffeine, it's going to increase your [11:49] levels of adrenaline and so-called [11:52] epinephrine, which will increase your [11:53] energy levels. It's going to decrease [11:55] levels of something called adenosine, [11:57] which builds up while you're sleepy. [11:58] It's going to make you feel less sleepy, [11:59] more alert, more energetic. That's sort [12:01] of obvious, but what's less obvious is [12:03] that it's increasing the number and [12:05] efficacy of dopamine receptors, so that [12:07] whatever dopamine happens to be around [12:09] in your system is going to have more of [12:11] a potent effect. So these are ways of [12:14] modulating more or less the baseline of [12:16] dopamine that you are able to produce [12:18] and the ways that dopamine can have its [12:20] action by way of binding to receptors [12:23] more potently. [12:24] Now there are other ways to increase [12:26] dopamine in a more acute or directed [12:29] way. Ways to spike your dopamine to [12:32] enhance your state of motivation, mood, [12:36] focus, and so on. If you're somebody who [12:38] has or is taking drugs for depression or [12:42] mania, please be very cautious about [12:44] manipulating your dopamine. In any case, [12:46] I don't just say that to protect us. I [12:47] say that to protect you. But if we were [12:50] to look at the supplement landscape and [12:52] ask which supplements increase dopamine, [12:54] there are a vast number of them. But the [12:57] three main ones, the most effective ones [12:59] that are readily available out there [13:01] without a prescription are mucuna [13:03] purines. This is actually the outside of [13:05] a velvety bean that has been extracted [13:07] and put into a supplement. Mchuna [13:09] purines is actual L-dopa. It's 99% [13:12] L-dopa which is a prescription drug that [13:15] is given for Parkinson's and for other [13:17] purposes where increasing dopamine is [13:20] important. I don't recommend mucuna [13:23] purines. I'm not saying that no one [13:24] should take it, but I don't take it and [13:26] I don't recommend it because it tends to [13:28] so potently and acutely increase [13:30] dopamine that there's a pretty [13:32] substantial crash afterwards. The other [13:34] two supplements that can increase [13:36] dopamine in a short-term way, but in a [13:40] significant way are elyroine. So, you [13:43] can buy that as a supplemented amino [13:45] acid. People vary tremendously in their [13:46] sensitivity to supplementing elyrocine. [13:49] I know people that can take two grams. I [13:51] know people that can barely take a 100 [13:53] milligrams. I know people that the best [13:55] dose for them is zero milligrams. So, [13:57] there's a lot of variation there [13:58] depending on sensitivity and their [14:00] natural baseline levels of dopamine and [14:02] whether or not they're doing a lot of [14:03] other things to support dopamine. But, [14:06] nonetheless, taking elyroine will lead [14:07] to fairly substantial increases in [14:10] dopamine within about 15 to 45 minutes [14:12] and it lasts for about 30 minutes to two [14:15] hours and then there's kind of a [14:16] tapering off. Some people experience a [14:18] little bit of an emotional or andor I [14:21] should say energetic crash. Some people [14:23] don't. And then the other supplement [14:24] that I certainly use and that I know a [14:27] number of other people use is more fast [14:28] acting but more potent which is [14:29] phenylthylamine. [14:31] This relates to the so-called PA [14:33] molecule Pa [14:36] and phenylthylamine increases dopamine [14:39] and some metabolites related to dopamine [14:41] in ways that really increase energy and [14:43] feelings of well-being and motivation. [14:45] And again, it's fast acting. So my [14:47] particular protocol, the one I use is [14:48] I'll take phenylthylamine at dosages of [14:52] about 300 to 600 milligrams along with [14:55] some elyroine or I'll take it on its own [14:58] with a molecule or I should say a [15:00] compound that we'll talk about a little [15:01] bit later as it relates to acetyloline [15:03] alpha GPC. But tyrrosine and [15:05] phenolthylamine taken alone or together [15:07] will make you feel more motivated and [15:09] more alert, more willing and able to [15:11] lean into particular motivated [15:13] behaviors, whether or not they're [15:14] physical or cognitive. But leaving that [15:17] aside, there are certain behavioral [15:19] protocols that are unrelated to your [15:22] overall goals and motivations that can [15:24] increase dopamine in a very sustained [15:26] way. And without question, the most [15:29] potent behavioral tool for doing that is [15:31] going to be deliberate cold exposure. [15:34] Deliberate cold exposure has been talked [15:36] about a lot here and elsewhere in terms [15:39] of its ability to do things like reduce [15:43] inflammation as a way to test and [15:46] improve resilience because uncomfortable [15:48] cold uh provided it's applied safely is [15:51] a great way to learn to be more [15:53] resilient because you're essentially [15:54] staying or forcing yourself to stay in a [15:56] circumstance where your system is [15:58] flooded with adrenaline. As I mentioned [16:00] before, dopamine tends to collaborate [16:02] with epinephrine and vice versa. Many [16:04] people will ask which protocols to [16:06] follow. Please see the episode on the [16:08] use of deliberate cold for health and [16:10] performance. You'll find that [16:11] hubbermanlab.com. So the use of cold [16:15] water for increasing dopamine is a real [16:17] tool. It's I would say a power tool. I [16:19] want to just briefly return to the fact [16:22] however that all of that is riding on [16:25] that phase one phase 2 background. [16:27] meaning it's probably going to take less [16:30] cold water exposure or I should say less [16:32] time doing cold water exposure early in [16:34] the day to get a big increase in [16:36] dopamine than it would later in the day [16:38] because later in the day your baseline [16:40] levels of dopamine are lower and you've [16:42] got more serotonin circulating. [16:44] That should make sense to you now as to [16:46] why that's the case. And does that mean [16:49] that you should really modify your [16:50] protocols dramatically? Probably not. [16:52] But you might keep that in mind that if [16:54] for instance you need to be in a highly [16:56] motivated focused state in the late part [16:58] of the day for whatever reason, it might [17:00] take a few or more of these tools in [17:02] combination in order to accomplish that. [17:04] Whereas if you're somebody who feels [17:05] pretty good during the day, but you're [17:06] kind of lacking motivation, you want to [17:08] increase dopamine levels and you don't [17:10] yet need to or want to resort to [17:12] prescription drugs or supplementation, [17:14] well then you might layer in a couple [17:15] behavioral protocols, paying attention [17:17] to, of course, the things that you might [17:18] be doing that would also potentially [17:20] suppress dopamine. So again, that kit of [17:22] tools is designed for you to play with. [17:26] If you choose, if it's safe for you to [17:28] apply them, then do that. Consider doing [17:30] them individually, not trying to hit all [17:33] the tools all at once, right? I mean, [17:35] why throw all those tools at your [17:37] dopamine system at once. Better would be [17:40] to have those tools in your kit and be [17:42] able to deploy them depending on whether [17:43] or not you're on travel, whether or not [17:45] you're eating well or less well, whether [17:47] or not you're sleeping well or less [17:48] well. That's highly individual. And I [17:50] like to think that in having those tools [17:52] in hand, you'll be able to adjust them [17:54] and apply them in the ways that allow [17:56] you to access the dopamine increases [17:59] that you're after. So next, I'd like to [18:00] talk about epinephrine, also called [18:02] adrenaline. I want to point out that [18:04] epinephrine is released both in the [18:07] brain and the body. In fact, there's a [18:09] barrier between brain and body that [18:11] prevents the epinephrine that's released [18:12] from your adrenal glands from crossing [18:15] the bloodb brain barrier. So your brain [18:17] has a separate site called the locus [18:19] ceruius. This is a collection of neurons [18:21] in the back of the brain that kind of [18:22] sprinkler the rest of the brain with [18:24] epinephrine [18:25] and essentially wakes up whatever neural [18:28] circuits happen to see or I should say [18:32] uh wake up any circuits where that [18:34] epinephrine happens to arrive right and [18:37] generally increase the excitability of [18:38] those networks. That's why we say [18:40] epinephrine increases energy. I'm not [18:43] talking about caloric energy, although [18:45] that's distantly related to this, but [18:47] really energy and the desire to move. [18:50] For many people, increasing adrenaline [18:53] or epinephrine might seem like a crazy [18:55] idea. Most people probably associate [18:57] this molecule with stress and they would [18:59] like to be less stressed. But there are [19:02] people, including me, that want to [19:04] increase our levels of epinephrine, at [19:06] least early in the day. I'm somebody who [19:08] wakes up rather slowly. In fact, I tend [19:10] to be kind of thinking about thinking [19:12] about maybe being in action early in the [19:15] day. But I try and push myself to get [19:18] into action which itself can increase [19:20] epinephrine. I should mention that any [19:22] physical activity, any physical [19:24] activity, walking, running, [19:26] weightlifting, swimming, even talking [19:29] for that matter is going to increase [19:30] levels of epinephrine. Locus ceruius is [19:34] a brain structure that is tightly [19:36] coupled with behaviors in a birectional [19:39] way. That is when you are in action you [19:42] increase the amount of epinephrine [19:44] released from locus rule you wake up the [19:46] brain and conversely when locus ceruius [19:50] is active the brain wakes up. So it's [19:52] reciprocal it goes both directions. So [19:54] keep that in mind. Exercise does indeed [19:56] give you energy. It burns caloric energy [19:59] but it gives you neural energy by way of [20:01] increasing epinephrine transmission from [20:03] locus ceruius. So we have exercise and [20:06] we have caffeine as potent tools for [20:08] increasing epinephrine and thereby [20:09] energy. Another potent tool that's [20:12] purely behavioral but is known to work [20:14] based on excellent studies in humans is [20:17] so-called cyclic hyperventilation. Some [20:19] of you may be familiar with Wimhof [20:21] breathing. There's also tumo breathing [20:23] which is very similar. Kundalini [20:25] breathing. All of those styles of [20:27] breathing involve cyclic [20:29] hyperventilation, deep inhales and [20:32] either passive exhales or active [20:34] exhales, but repeating inhale, exhale, [20:36] inhale, exhale in a very deep and [20:37] repetitive way. If you did that for 25 [20:41] repetitions, 25 inhales and exhales, you [20:44] would feel more alert. You'd also feel [20:45] more warm. Why? Because you've increased [20:48] epinephrine adrenaline release in the [20:50] brain and body. It works the first time [20:52] and it works every time to increase [20:54] epinephrine and thereby energy. If you [20:56] do that over and over, you're going to [20:58] be very alert. You're going to have more [20:59] energy. You're going to feel like you [21:00] want to move around a lot more. In fact, [21:02] you might even feel agitated. So, people [21:04] with a lot of anxiety or prone to panic [21:06] attack might want to be cautious in how [21:07] they train and embark on that type of [21:10] breathing. Might want to approach it a [21:11] little more carefully or avoid it [21:12] altogether. But for most people, cyclic [21:14] hyperventilation is simply going to get [21:15] you more energized and feeling like you [21:17] want to move, feeling like you can think [21:19] more clearly, and you will be more [21:21] wideeyed and alert because you are [21:23] releasing adrenaline. And the cold water [21:25] exposure protocol that I talked about [21:27] earlier and that's covered in our [21:28] episode on cold and in the newsletter on [21:30] cold. Well, that as I mentioned earlier [21:33] potently increases dopamine, but also [21:36] epinephrine. Now, we can't really say [21:38] that there are foods to increase [21:40] epinephrine. There are of course [21:42] prescription drugs that will increase [21:43] epinephrine and of course there are all [21:46] sorts of so-called beta blockers that [21:48] will block the receptors for epinephrine [21:50] to make you feel calm for public [21:52] speaking or for various heart conditions [21:55] etc. That's really the domain of [21:56] physicians and should really be worked [21:58] out with your cardiologist with a [22:00] physician etc. I think the tools of [22:03] exercise and should you want very potent [22:07] increases in adrenaline, highintensity [22:09] exercise, as well as the tools of [22:12] caffeine, cyclic hyperventilation, and [22:14] deliberate cold exposure really combined [22:16] to give you a nice little kit, I would [22:19] say a versatile kit of ways to increase [22:22] epinephrine for sake of having more [22:24] physical and mental energy. So, next is [22:26] the neuromodulator acetylcholine. And as [22:29] I mentioned earlier, acetylcholine is [22:31] associated with states of focus. And [22:34] those states of focus can be high energy [22:36] states of focus. So the ones that are [22:39] accompanied by high levels of dopamine [22:41] and epinephrine and where we're really [22:44] excited about and really lasered in on [22:46] something. or they can be the calmer, [22:49] more relaxed states of focus like [22:51] reading a book or practicing music or [22:54] listening very carefully to somebody in [22:56] a way that's relaxed and calm. Now, ways [22:58] to increase acetylcholine in a potent [23:01] way include again nutrition and [23:04] supplementation. It is important to have [23:07] baseline levels of acetylcholine be [23:10] sufficiently high as well. And for that, [23:12] the ideal situation is to regularly [23:14] ingest foods that provide enough of the [23:16] precursors for acetylcholine to be made. [23:18] Eggs contain a lot of choline. Beef [23:20] contains choline. Soybeans contain [23:22] choline. So there are vegan or non-meat [23:24] sources. Chicken, fish, mushrooms, [23:27] kidney, beans, these sorts of things [23:28] contain a lot of choline. And there are [23:30] other vegetables that contain choline. [23:31] So depending on your dietary preferences [23:33] and needs, you can um select certain [23:35] foods uh to ingest to get enough choline [23:38] to synthesize enough baseline [23:39] acetylcholine. [23:42] In the realm of supplementation, there [23:44] are some excellent tools for increasing [23:46] acetylcholine in the acute short term, [23:49] meaning over the course of about 30 [23:52] minutes out to about 2 hours or maybe [23:54] even four hours. The most common of [23:55] those molecules is actually nicotine. [23:57] Nicotinic acetyloline receptors are [24:00] abundant throughout the body and brain. [24:02] They're in various brain circuits. They [24:04] are on muscle. And yes, smoking nicotine [24:08] either by vaping or cigarette will [24:10] activate those nicotinic receptors. But [24:14] of course, smoking is a terrible thing. [24:16] It will also activate things like lung [24:18] cancer. So, I definitely don't recommend [24:20] that. It also activates addiction [24:22] because of the ways that it triggers [24:24] activation of the dopamine circuits. [24:26] However, some people will chew nicarette [24:30] or other nicotine type gums. Some people [24:32] are very sensitive to ingested nicotine. [24:35] Some people take it and feel absolutely [24:37] terrible. But some people do use them as [24:39] cognitive enhancers. Supplements that I [24:41] have used and do use for increasing [24:43] acetylcholine [24:45] are things like alphagpc [24:48] or hooperine. AlphaGPC [24:52] is in the choline pathway such that more [24:55] acetylcholine is synthesized after you [24:57] ingest it. That's the general logic or [24:59] framework of how it works. Whereas [25:01] hooperine is mainly in the enzyatic [25:03] pathway. It tends to adjust how much [25:06] acetylcholine is broken down and lead to [25:08] net increases in acetylcholine. I will [25:12] often take 300 milligrams of alpha GPC [25:14] prior to workouts or prior to cognitive [25:17] work bouts. I tend to take it alongside [25:19] caffeine and phenyl ethylamine. So I [25:22] take that in combination either before [25:24] workouts or workouts. Really sharpens my [25:26] focus and again I'm doing that three [25:28] maybe four times per week. And I'm [25:29] careful to do that in the early part of [25:31] the day so that it does not disrupt my [25:33] sleep. So let's discuss serotonin. [25:35] Serotonin as I mentioned earlier is [25:37] associated with brain and body states of [25:40] well-being, of comfort, of satiety. And [25:43] therefore, it should come as no surprise [25:44] that a lot of the prescription drug [25:46] treatments for things like depression [25:48] involve increasing levels of serotonin [25:50] in the brain and body. That said, [25:53] anytime you talk about prescription [25:54] drugs for serotonin, we also want to [25:57] acknowledge that there are often side [25:59] effects associated with increasing [26:00] serotonin. In particular, if serotonin [26:02] levels go too high, that is if the [26:04] dosages of those treatments go too high. [26:06] People will, for instance, feel reduced [26:09] appetite, reduced libido, increased [26:11] lethargy, etc. And there's a so-called [26:13] serotonurgic syndrome. That said, there [26:16] are behavioral tools, nutritional tools, [26:18] and supplementation tools that can tap [26:20] into the serotonin system. Not to the [26:22] same degree in potency, but nonetheless, [26:24] in ways that can still impact our [26:26] feelings of well-being in positive ways. [26:29] What sorts of things? Well, for [26:32] instance, physical contact, things like [26:34] holding hands, believe it or not, hugs, [26:37] cuddling, etc., can increase serotonin [26:40] transmission and they make people feel [26:42] good. This shouldn't really come as a [26:44] surprise. There's also gratitude and we [26:46] did an entire episode about gratitude. [26:48] There's a lot of misunderstanding about [26:49] gratitude. Turns out, first of all, that [26:52] receiving, not giving gratitude is what [26:55] has the most potent effects on [26:56] increasing serotonin and activity of the [26:58] brain circuits that involve serotonin [27:01] and that lead to increases in feelings [27:02] of well-being. This is interesting. [27:05] receiving much more than giving [27:08] gratitude is what activates those [27:10] serotonin pathways. The other thing [27:12] about gratitude that's somewhat [27:13] counterintuitive is that observing [27:16] others giving and receiving gratitude is [27:18] immensely powerful for evoking serotonin [27:21] and the activity of serotonergic [27:23] circuits in you the observer. So [27:26] receiving and observing gratitude turns [27:28] out to be the most potent way to [27:30] increase serotonin in the brain and [27:32] body. Now, what about nutritional [27:35] approaches to increasing serotonin? [27:37] Well, just as we have tyrrosine as an [27:39] amino acid precursor upstream of [27:41] dopamine synthesis, [27:43] we have the amino acid tryptophan, which [27:47] is upstream of serotonin synthesis. And [27:50] one simply has to go online and put in [27:53] tryptophan containing foods and you will [27:55] discover that there are a lot of foods [27:56] that are enriched in tryptophan that can [27:59] lead to net increases in the amount of [28:00] serotonin available in the brain and [28:02] body. Now one molecule that I've found [28:04] to be particularly interesting and [28:06] useful and this is one that I haven't [28:07] talked about yet on this podcast is [28:10] inositol in particular myoininoitol. [28:13] Myioininoitol can have the effect of [28:16] increasing serotonin and other [28:19] neurochemicals but primarily at least in [28:21] terms of the neurom modulators discussed [28:23] today serotonin. I've been taking 900 [28:26] milligrams of myioinostol [28:28] every third night or so as a test of its [28:30] ability to improve sleep. And I have to [28:32] say the depth and quality of sleep that [28:35] I've been obtaining on myositol is [28:38] pretty remarkable. And of course, I [28:40] should mention that no supplement, [28:42] either added or withdrawn from your [28:44] protocol, should ever be used as a [28:47] direct replacement for prescription drug [28:49] treatments that your physician has given [28:50] you. You should always talk to your [28:51] physician anytime you remove or add [28:53] something to your drug protocol or [28:55] prescription protocol. Of course, again, [28:57] this is a general theme of all four of [28:59] these neurom modulators, dopamine, [29:01] epinephrine, acetylon, and serotonin. [29:03] You want to make sure that you have [29:05] sufficient baseline levels of those [29:08] things through things like diet, regular [29:10] behaviors, and then you have the [29:12] opportunity to use supplementation and [29:14] if it's appropriate for you, [29:16] prescription drugs, and certain [29:17] behavioral protocols to try and get [29:19] these potent increases, these acute [29:21] increases in whichever the neurom [29:23] modulators you happen to want to [29:25] leverage for your particular goals. So [29:27] that brings us to the end of at least [29:29] this exploration of the neurom [29:30] modulators, dopamine, epinephrine, [29:33] acetyloline, and serotonin. Whether or [29:36] not you're using nutritional tools or [29:38] supplementation or prescription drugs or [29:41] any other sort of protocol to try and [29:44] create a desired effect of focus or [29:47] energy, motivation, relaxation, [29:50] you are playing with the same [29:52] neurochemical ingredients. So what I'm [29:55] hoping is that rather than decide that [29:57] any one tool is the most useful or that [30:00] any one neurochemical is most useful for [30:02] that matter that the information that [30:04] I've provided today allows you a kit of [30:08] versatile tools that allows you to [30:10] figure out what levels of dopamine and [30:13] augmentation of dopamine are appropriate [30:16] and necessary for you. what levels of [30:19] acetylcholine and tools for manipulating [30:21] acetylcholine are going to be most [30:23] useful for you and so on and so forth. [30:25] So, I'd like to thank you once again for [30:27] joining me today in our discussion about [30:29] these incredibly powerful molecules we [30:31] call neurom modulators and the things we [30:34] can do and take in order to control them [30:38] so that we can enhance our mental [30:39] health, physical health, and [30:40] performance. And last, but certainly not [30:43] least, thank you for your interest in [30:45] science. [30:47] >> [music]