Stanford's Williams Shrinks TMS Therapy to Five Days for Acute Depression

斯坦福学者Williams将急性抑郁症TMS疗法缩短至五天 抑郁症是一种电生理回路故障而非化学失衡，加速脑刺激方案因此能在数天内达到90%的缓解率。 该节目探讨了向“精神病学3.0”的范式转变，即将心理健康疾病重新定义为高度可纠正的神经回路问题，而非永久性的化学失衡。Nolan Williams博士解释了先进的经颅磁刺激（TMS）方案，如为期5天的斯坦福神经调节疗法（S&T），如何利用间隔学习理论快速使脑心连通性恢复正常，并使重度抑郁症实现高缓解率。此外，讨论还评估了致幻剂化合物（包括MDMA、裸盖菇素、伊博格碱和死藤水）在安全打破僵化、不良的创伤循环以推动持久的行为改变和心理康复方面的临床疗效及神经生物学机制。 抑郁症是一种严重削弱能力的疾病，目前已被美国心脏协会正式认定为与高血压、高脂血症和糖尿病并列的冠状动脉疾病第四大主要危险因素。 (0:06) Nolan Williams博士旨在针对急性、高危环境下的精神科急症，开创基于大脑的快速解决方案，从而超越口服抗抑郁药等传统门诊治疗方式。 (0:06) 经颅磁刺激（TMS）依据法拉第定律运作，利用从背外侧前额叶皮层到迷走神经的物理与电通路来减缓心率。 (2:51) 成功的快速TMS能够重新校准大脑的调控机制，带来深刻的正念与临在状态，早期获得缓解的患者会自发报告体验到强烈的当下临场感。 (5:28) 广为流传的“化学失衡”理论存在根本缺陷，因为SSRI类药物疗效的延迟出现表明，其疗效实际上是由下游大脑可塑性所驱动的。 (7:52)

Dr. Nolan Williams argues that psychiatry is entering a circuit-based era where rapid neurostimulation and medically supervised psychedelics can resolve severe depression and trauma by directly reconfiguring dysregulated neural pathways. Psychiatry 3.0: Moving Beyond Chemical Imbalances (7:52) Williams frames modern mental healthcare across three eras: Psychiatry 1.0, centered on psychoanalysis and upbringing; Psychiatry 2.0, defined by daily medication and the chemical imbalance hypothesis; and Psychiatry 3.0, focused on circuit-level electrophysiology. Williams points out that although selective serotonin reuptake inhibitors (SSRIs) are clinically effective for disorders such as panic and OCD, their multi-week delay in relieving symptoms indicates that therapeutic benefits stem from downstream neuroplasticity rather than an immediate correction of serotonin deficits. Emphasizing the physical severity of mood disorders, he notes that the American Heart Association recently designated depression as the fourth major risk factor for coronary artery disease alongside hypertension, hyperlipidemia, and diabetes. Under the Psychiatry 3.0 paradigm, depression is reframed as an electrophysiological circuit failure akin to a cardiac arrhythmia. Williams argues that targeting these circuits directly can restore mood regulation in a matter of days without altering a patient's core identity or relying on long-term daily chemical supplementation. Accelerated Neuromodulation via Spaced Learning (31:54) To address acute psychiatric emergencies in hospital settings, Williams's team developed the Stanford Neuromodulation Therapy (S&T, formerly SAINT) protocol. Utilizing Transcranial Magnetic Stimulation (TMS) under Faraday's law, magnetic pulses pass through the skull to induce electrical currents in the dorsolateral prefrontal cortex. This signal cascades downward through the anterior cingulate, insula, amygdala, and nucleus tractus solitarius before traveling along the vagus nerve to slow heart rate. This physical pathway reinstates prefrontal executive governance over the cingulate, suppressing spontaneous negative thoughts. Rather than using conventional six-week schedules of once-daily stimulation, the protocol applies spaced learning theory, which demonstrates that the brain optimizes retention when exposed to signals every 60 to 90 minutes. S&T delivers 10 hourly sessions per day over five days, compressing roughly seven and a half months of standard TMS into a 50-hour block. Williams reports that clinical trials and open-label studies show 60% to 90% full remission rates within one to five days, with remissions documented between one and four years in some patients. Circuit Convergence Across Psilocybin and Neurostimulation (18:27) Neuroimaging research demonstrates that both effective TMS and psilocybin act on the same anatomical mechanism: down-regulating excessive connectivity between the subgenual anterior cingulate and the default mode network. In depressed patients, this hyper-connected circuit binds self-representation to negative emotional valence. Both treatments uncouple this loop, shifting the brain from a localized 'small world' network into a globally integrated 'large world' connectivity state. Clinical outcomes reflect these structural resets. In psilocybin trials, remission rates reach approximately one-third in blinded studies and 50% to 66% in open-label settings. Similarly, a clinical trial of MDMA using 150 to 175 milligram doses produced clinically significant PTSD relief in approximately two-thirds of participants, with therapeutic effects enduring for years. Williams contrasts this durability with ketamine infusions, where symptomatic relief lasts an average of only 1.5 weeks and necessitates recurring treatments. High-Risk Alkaloids and Controlled Medicalization (21:07) Williams examines more intensive ethnobotanical treatments, including ibogaine and ayahuasca. Ibogaine, an alkaloid from the West African iboga tree lasting 24 to 36 hours, induces an objective 'life review' state. In a study evaluating special operations veterans with post-traumatic stress and moral injury from combat, Williams observed marked reductions in trauma and guilt. However, ibogaine carries dangerous cardiac risks that mandate pre-treatment electrocardiogram (ECG) screening. Meanwhile, Brazilian studies of Amazonian ayahuasca—which pairs oral DMT with a plant-derived reversible MAOI—found statistically significant reductions in prison recidivism. Williams stresses that these compounds must be disentangled from 1960s counterculture and restricted entirely to supervised medical protocols. He argues that because standard psychiatric medications with mild effects require ongoing medical oversight, permitting unsupervised recreational access to powerful, mind-altering psychedelics would be medically irresponsible. While rapid neuromodulation and psychedelic interventions demonstrate rapid and substantial remission rates, the long-term durability of outcomes and optimal maintenance protocols remain active areas of clinical investigation that require strict medical supervision.

精神病学与行为科学教授 Nolan Williams 指出，精神医学正迈向聚焦神经环路与电生理干预的“精神医学 3.0”时代；通过将间隔学习理论应用于靶向神经调控，以及在严格医疗监管下应用致幻剂，临床上能够对重度抑郁和创伤后应激障碍实现快速且持久的重塑。 精神医学3.0范式与脑心回路机制 (2:51) Williams 医生提出精神医学的发展历程已跨越三个阶段：以弗洛伊德心理分析和早期经历为核心的“1.0 时代”，以化学失衡理论和长期口服药物为特征的“2.0 时代”，以及当前以神经环路与电生理学为重心的“3.0 时代”。他指出，传统的单胺类化学失衡假说已被证实存在缺陷，抗抑郁药物数周起效的现实反映其本质是通过下游神经可塑性起效。针对抑郁症，经颅磁刺激（TMS）利用法拉第电磁感应原理，无需外部化学物质即可在 1 至 5 天内诱导电流并使大脑皮层神经元去极化。此外，美国心脏协会已将抑郁症列为继高血压、高血脂、糖尿病之后的第四大冠状动脉疾病独立危险因素。脑成像显示，刺激背外侧前额叶皮层后，信号沿前扣带回、脑岛、杏仁核、孤束核下行，经迷走神经直达心脏引发心率减速，该通路已被荷兰 Martin Arns 等国际团队独立重复验证 4 至 5 次，证实了脑心电生理轴的物理存在。 基于间隔学习理论的S&T加速方案 (31:54) 为了应对精神科急性住院患者缺乏快速有效干预手段的困境，Williams 团队开发了斯坦福神经调控疗法（S&T，原称 SAINT）。传统 TMS 采用每天一次、每周五天且持续六周的给药模式，不仅忽视了大脑信息保留机制，且存在剂量严重不足的问题。S&T 方案借鉴认知科学的“间隔学习理论”（即大脑对间隔约 1 至 1.5 小时的刺激具备最佳学习与神经巩固效率），将长达七个半月的常规刺激总量压缩至连续 5 天的 50 小时治疗块内。患者每天接受 10 小时周期、每小时一次且全天累计 90 分钟的规律脉冲，促使背外侧前额叶恢复对扣带回冲突检测系统的抑制功能。临床试验及开放标签数据显示，60% 至 90% 的患者在 5 天内达到情绪完全缓解，且随访中部分个体维持无症状状态达 1 至 4 年，同时显著降低了患者因病耻感而产生的长期自我归因创伤。 致幻剂对创伤与默认网络回路的解耦 (16:18) 在致幻分子研究中，Williams 强调必须摒弃 1960 年代的反文化标签，以严格的循证医学视角审视其治疗价值。针对创伤后应激障碍（PTSD），在 MAPS 单次或两次 150 至 175 毫克的医用监管剂量下，约三分之二（66%）的患者获得临床显著改善，且早期随访显示其疗效可维持数年，表现远优于单次输注平均仅维持 1.5 周的氯胺酮。在抑郁症治疗中，盲法与开放标签研究显示赛洛西宾可使三分之一至三分之二的患者缓解。神经影像学研究揭示，赛洛西宾并非常规推测的大脑兴奋剂，而是诱导全脑整体活动减弱，同时促使局部“小世界”网络重组为广泛连通的“大世界”架构。赛洛西宾与 S&T 方案在机制上高度收敛：二者均能有效下调胼胝体下默认网络与扣带回之间的异常超连接，阻断负面情绪与自我表征的病态纠缠，使神经环路脱离固化死锁。 特殊植源性分子的神经行为矫正效应 (21:07) 源自非洲加蓬的依波加因（Ibogaine）是一种作用时间长达 24 至 36 小时的单萜生物碱。因其不具备娱乐快感且伴随显著心脏毒性，团队通过严格的心电图（ECG）筛选开展了针对海豹突击队等特种作战退伍军人的神经认知评估。初步数据显示，该物质促使患者在闭眼状态下以“客观超然的同理心”重演早期记忆，对特战人员因战时附带平民伤亡引发的严重“道德损伤”（Moral Injury）产生了显著的自我原谅与创伤消退效果。另一方面，由含 DMT 植物与含可逆性单胺氧化酶抑制剂（MAOI）植物共煮而成的亚马逊死藤水（Ayahuasca），展现了高度精确的民族植物化学配比，既避免了不可逆 MAOI 诱发致命五羟色胺综合征的风险，又能阻断肠道酶解并促使 DMT 穿透血脑屏障。巴西针对服刑人员的对照实验显示，接受死藤水干预的组别出狱后再犯率呈统计学显著下降，凸显了神经可塑性分子重塑深层行为模式的临床潜力。 针对精神疾病的干预范式正逐步由经验性药物维持转向靶向电生理重置与受控可塑性诱导。尽管依波加因的心脏风险、氯胺酮疗效短暂以及 S&T 协议的长期维持剂量需求仍有待进一步追踪，但严格医疗监管下的精准环路干预为急症精神医学提供了全新的客观临床路径。

[2:51] Dr. Nolan Williams: wasn't trying hard enough. [5:28] Dr. Nolan Williams: In one case, it's like the coach telling the player what to do and in the other case it's like a player telling the coach what to do and you you restore order to the game. [5:28] You know, I was driving back to my hotel and I decided to go to the beach and I just sat there and I was totally present in the present moment for an hour. [7:52] chemical imbalance [7:52] Dr. Nolan Williams: Psychiatry 1.0 [7:52] schizophrenogenic mother. [7:52] Dr. Nolan Williams: Psychiatry 2.0 [7:52] Dr. Nolan Williams: Psychiatry 3.0 [7:52] chronically broken [13:51] Dr. Nolan Williams: highly adaptive. [21:07] 10 years of psychotherapy in a night. [21:07] moral injury [24:53] straight scientists looking at this [24:53] Dr. Nolan Williams: preposterous [24:53] Dr. Nolan Williams: dumb moment [31:54] turn on, stay on, remember to stay on.

[0:06] Welcome to Huberman Lab Essentials, [0:08] where we revisit past episodes for the [0:10] most potent and actionable [music] [0:12] science-based tools for mental health, [0:14] physical health, and performance. [0:17] I'm Andrew Huberman and I'm a professor [0:19] of neurobiology and opthalmology at [0:22] Stanford School of Medicine. And now for [0:24] my discussion with Dr. Nolan Williams. [0:26] Thanks for joining today. I'm really [0:28] excited to have this conversation. I [0:30] have a lot of questions about different [0:33] compounds, psychedelics in particular. [0:35] >> Yeah. [0:36] >> But before we get into that discussion, [0:38] I want to ask you about depression, [0:40] broadly speaking. [0:41] >> Sure. [0:42] >> I heard you say in a wonderful talk that [0:44] you gave that depression perhaps the [0:47] most debilitating condition worldwide. [0:50] Yet in contrast to other medical [0:52] conditions like cancer, we actually have [0:55] a fairly limited number of tools to [0:57] approach depression. And yet the number [0:59] of tools and the potency of those tools [1:01] is growing. [1:02] >> Depression is u the most disabling [1:05] condition worldwide. Um what's [1:07] interesting about depression is it's [1:08] both a risk factor um for other [1:12] illnesses and it makes other medical and [1:14] psychiatric illnesses worse. Right? So [1:17] recently the American Heart Association [1:19] added depression as the fourth uh major [1:22] risk factor for coronary artery disease. [1:24] Right? So alongside the the risk factors [1:27] that we know hypertension, high blood [1:29] pressure, hyper lipidmia, high [1:31] cholesterol and diabetes, you know, high [1:34] blood sugar, those three have been on [1:36] the list for a long time and depression [1:38] end up, you know, being added to the [1:39] list as the fourth one. A lot of what [1:41] we're doing in the lab actually is um is [1:43] measuring kind of brain heart [1:45] connections and we can actually with [1:47] transcranial magnetic stimulation a form [1:49] of brain stimulation we can actually [1:50] decelerate the heart rate we can capture [1:52] that heart rate deceleration um over the [1:55] mood regulatory regions and so actually [1:57] a direct probe of that connection. We've [2:00] been very interested in a very [2:01] particular um clinical set of problems [2:05] around the the most severe and the most [2:08] high acuity settings that folks with [2:11] depression end up being in and that's in [2:14] you know emergency settings where they [2:16] go into inpatient units. the field [2:18] really hasn't developed a way of um you [2:21] know consistently being able to treat [2:22] that problem and folks end up getting [2:24] the same standard oral anti-depressants [2:26] that they've been getting outpatient and [2:29] and I came to this because I've you know [2:32] dual trained as a neurologist and [2:33] psychiatrist went back and forth between [2:35] neurology and psychiatry saw that in [2:38] neurology we have all of these ways of [2:40] treating acute brainbased problems and [2:43] really wanted to emulate that in [2:45] psychiatry and find ways to develop and [2:47] engineer new, you know, brainbased [2:49] solutions. [2:51] >> Many people out there probably think of [2:52] the relationship between the the heart [2:54] and the mind as kind of woo or kind of a [2:57] a soft biology. But here you're talking [2:59] about an actual physical connection. [3:01] >> Y what area of the brain is it? [3:03] >> You know, the first place where the [3:05] stimulation goes is called the [3:06] dorsalateral prefrontal cortex. It's [3:08] kind of the sense of control kind of [3:10] governor of the brain. And then it'll [3:12] and then what we know is that when you [3:14] use a magnet kind of what we call [3:16] Faraday's law this idea of um using a [3:19] magnetic pulse to induce uh an [3:22] electrical current in electrically [3:24] conducting substances. So in this case [3:26] brain tissue but not skull or sk sc [3:28] scalp or any of that or hair you avoid [3:31] all that just the brain tissue. Then you [3:33] have a direct depolarization of cortical [3:36] neurons, you know, the surface of the [3:38] brain's neurons in this dorsal [3:41] prefrontal. And if you do that in the [3:44] actual scanner, which we can do, you can [3:46] see that that distributes down into the [3:49] anterior singulate in the insula and the [3:51] amydala and ultimately the tract goes [3:54] into something called the nucleus tract [3:56] of solitarius and ultimately into the [3:58] vagus nerve into the heart. So the the [4:01] heart uh very consistently seems to be [4:04] the end organ of the uh dorsal [4:06] prefrontal cortex and if you do that [4:08] over visual cortex you don't get that or [4:11] motor cortex you don't get any of those [4:12] findings it's really specific to this [4:15] kind of control region of the brain and [4:18] so yeah it seems to you know it's our [4:21] work other other folks work Martin ARS [4:23] in um in in Europe uh the Netherlands [4:26] work showing the same connections I [4:28] think it's been replicated like four or [4:29] five times where I think TMS is really [4:32] interesting. Actually, we had a lot of [4:33] patients who've told me like my my [4:35] therapist told me that I wasn't trying [4:37] hard enough in therapy. [snorts] [4:38] These are, you know, moderate to pretty [4:40] severe depressed patients. And as soon [4:42] as we get them well with with the TMS [4:44] approaches, you know, kind of rapid, you [4:47] know, 5day approach, and the next week [4:48] we come in and see them and they'll say, [4:50] you know what I did all weekend is I [4:51] looked at my therapy books and now I can [4:53] understand it. And so, you know, I [4:56] actually see TMS as a way of having kind [4:58] of exogenous sorts of cognitive [5:02] functions that in milder forms of [5:05] depression, we can pull off with [5:07] psychotherapy. You know, this idea of [5:09] being able to kind of turn that [5:11] prefrontal cortex on and have it govern [5:14] these deeper regions. In depression, the [5:17] deeper regions govern the prefrontal [5:20] cortex. In one case, it's like the coach [5:22] telling the player what to do and in the [5:24] other case it's like a player telling [5:25] the coach what to do and you you restore [5:27] order to the game. [5:28] >> You restore order to the game and what [5:30] it looks like is depression is a bunch [5:32] of kind of spontaneous content that's [5:35] semi valitional that's being kind of [5:37] generated out of this conflict um [5:40] detection system. the singulate. In [5:42] depression, it looks like the left [5:44] dorsal lateral does not sufficiently [5:47] clamp down on it. And what therapy [5:50] appears to do is to kind of restore [5:52] that. What we see with TMS over that [5:55] region is that we just exogenously do [5:58] the same sort of thing. We restore the [6:00] governance of the left dorsal lateral [6:03] over the singulate area and that is [6:06] correlated with treatment improvement. [6:08] So the degree in which you can re- time [6:12] or reeregulate in time the left dorsal [6:15] lateral over the singulate, the more of [6:17] an anti-depressant effect you have. TMS [6:19] is almost like exercise for the brain, [6:21] right? You're kind of exercising this [6:23] region over and over again with a [6:24] physiologically relevant signal and kind [6:27] of turning that system on. And what's [6:30] interesting for this show is, you know, [6:32] we had a couple of folks um you know, [6:34] probably five or six folks that have [6:35] actually told me this where if they [6:36] remit early enough in the week, we have [6:38] this very dense stimulation approach [6:40] where we can stimulate people really [6:42] rapidly over a 5day block. By Wednesday, [6:45] they're like totally zero down on the [6:47] depression scales, you know, even better [6:49] than most people walking around, like [6:51] really no anxiety, no no depression or [6:53] anything. By Thursday, the first guy [6:56] that that told me this, he came in and [6:57] he said, "You know, I was driving back [6:59] to my hotel and I decided to go to the [7:01] beach and I just sat there and I was [7:03] totally present in the present moment [7:05] for an hour." And he's like, "I read [7:07] about this in my mindfulness books, but [7:08] I experienced it last night and I've [7:11] never experienced anything like this [7:12] before." And I was like, "hm, that's [7:14] interesting, but kind of wasn't sure." [7:16] And then and then I didn't tell any, you [7:18] know, obviously any more patients about [7:20] that. And then about five over the last [7:21] couple of years when they get they were [7:23] mid early in the week by the end of the [7:25] week they're like going to the beach and [7:27] they're like totally having a what [7:28] people describe as a pretty mindful [7:31] present moment sort of experience which [7:33] is really interesting you know what that [7:35] is. I mean, I don't have full-on [7:38] scientific data to tell you, but it it's [7:40] just it's a it's an interesting [7:42] anecdote, right, that that folks when [7:44] you push them through this point of of [7:46] feeling kind of clinically well that [7:49] some people end up reporting this [7:50] additional set of features. So, [7:52] >> I want to make sure that before we dive [7:54] into ketamine and psilocybin that we do [7:57] touch on SSRI, selective serotonin [7:59] reuptake inhibitors, because we can't [8:00] really have a discussion about [8:01] depression without talking about SSRIs. [8:03] My understanding is that the SSRIs are [8:06] powerfully effective for certain forms [8:08] of obsessive obsessivempulsive disorder [8:10] and may also be effective for treatment [8:12] of depression. Is that right? And how [8:14] should we think about SSRIs? Are they [8:15] useful? Are they not useful? SSRIs [8:17] clearly work. Um, you know, many many [8:21] metaanalyses kind of proving that out, [8:23] right? That that in a subopul of [8:26] individuals, they achieve great benefit [8:28] for depression, for obsessivempulsive [8:30] disorder, for generalized anxiety [8:32] disorder, panic, you know, all these [8:34] things, you can see an improvement in [8:36] those symptoms um with what we call [8:38] SSRIs or selective serotonin reuptake [8:41] inhibitors. The issue is that they don't [8:43] work immediately, right? So they don't [8:44] work like the same day you start taking [8:47] them. And that that suggests that [8:49] probably it's not exactly the serotonin [8:52] being in there that's directly driving [8:55] it. That it's much more likely that it [8:57] may have some brain plasticity effects, [8:59] right? There's not a deficit of [9:01] serotonin. You're not born with uh what [9:05] people call a chemical imbalance. And [9:06] psychiatry has known this. This is not [9:08] actually new information anybody, you [9:10] know, it's kind of a rehashing of a [9:13] bunch of information we've known for a [9:14] while now. But in the lay press, it's [9:16] kind of hit in a way that it didn't seem [9:19] to to grab attention um before with [9:22] previous publications. But this idea [9:24] that this chemical imbalance idea is [9:26] wrong. I really think that part's [9:28] important because I think that what I'll [9:30] call psychiatry 1.0, right? this kind of [9:32] idea of Freud and and psychotherapy and [9:35] its and its origins. Um, it was a lot [9:38] around, you know, the your family and [9:41] those experiences and psychotherapy kind [9:43] of going in and correcting or helping [9:45] you to figure out or, you know, show you [9:48] being able to see or people hear you so [9:51] that you can eventually come to the [9:53] conclusion of certain cognitions that [9:56] aren't helping you, right? Things like [9:57] the schizophrenogenic mother and all of [9:59] that, you know, that was a concept at [10:00] some point, right? And so we've [10:03] transitioned from that to to the you [10:05] know for a long time the chemical [10:06] imbalance which I'll call psychiatry [10:09] 2.0. You know this idea that there's [10:12] something chemically missing. The [10:15] trouble there for a patient right is [10:17] that it's telling it's sending a message [10:19] of there's something missing with me. [10:22] Whether it be my experiences I had no [10:24] control of over when I was a child or um [10:26] a chemical in my brain. What I think's [10:29] really powerful with with TMS, [10:32] um, you know, really powerful with TMS [10:35] and a level even powerful with the [10:36] psychedelic story is it's saying [10:39] something different. You know, TMS works [10:42] and there's no serotonin coming in or [10:44] out of the brain, right? And we're doing [10:46] a rapid form of TMS that works in 1 to 5 [10:49] days. So, there's no there's it's very [10:51] unlikely that there's some long-term [10:53] kind of upregulation of serotonin that's [10:56] driving that. So our work actually kind [10:58] of pushes back on this serotonin [11:00] hypothesis as being kind of the center [11:02] of depression because it says look we're [11:04] not giving anybody any serotonin. We're [11:07] simply turning these brain regions on [11:09] and we're focused on the circuitry and [11:12] that's psychiatry 3.0. It's not just [11:13] like neurom modulation. Neurom [11:15] modulation is a really nice you know use [11:17] case for psychiatry 3.0 because it's a a [11:19] way to focally and directly perturb [11:22] brain regions in in whatever modality [11:24] you're using. But you know there are a [11:26] lot of a lot of groups that are actually [11:28] doing neuroiming before and after and [11:30] they're able to see circuit level [11:32] changes for something like psilocybin or [11:34] ketamine long after the drug is gone. [11:38] Right? Suggesting in those same brain [11:40] regions converge. So the subgenial [11:43] default mode network connection that we [11:44] see is changing with our our our stand [11:47] um Stanford neurom modulation therapy [11:49] technique. It's that same set of brain [11:52] regions that that ketamine and uh [11:55] psilocybin seem to act on act on these [11:57] connections between brain networks that [12:00] seem to shift. And so it refocuses the [12:04] story on something that's highly [12:06] correctable and it's it's basically [12:09] electrphysiology [12:11] and it's basically kind of recalibrating [12:15] a circuit that is re-calibratable [12:18] instead of I have something missing or I [12:21] have some set of experiences early in [12:23] life that are um that are going to [12:25] forever trap me in these these [12:27] psychiatric diagnoses. And so it kind of [12:30] challenges that idea. And I think that's [12:31] what's so powerful about psychiatry 3.0. [12:35] Um this idea of focusing on the circuit [12:37] because it gets us gets us into thinking [12:39] about psychiatry and psychiatric [12:41] illnesses is something that are [12:43] recoverable. People can get better. [12:45] People, you know, we've seen with our [12:47] TMS techniques, we've seen it with with [12:48] some of the psychedelic work that we've [12:50] done where people are actually in normal [12:53] levels of mood for sustained periods of [12:55] time or [12:56] >> within 5 days [12:57] >> within five or less days. And in the [12:59] case of of the psychedelics within a few [13:01] days, right? So we can get people out of [13:04] these states, they're totally well. [13:06] There's no drug in their system at that [13:08] point. In the case of the psychedelics, [13:09] it was never a drug in their system in [13:11] the case of of TMS. And it and it just [13:14] tells us that that it's it's it's [13:16] fixable. It's just like an arrhythmia in [13:17] the heart. It's like a broken leg. We [13:19] can go in and do something and we can [13:21] get somebody better. Then I think what's [13:23] what's empowering and what a lot of [13:25] patients have told me is they say you [13:27] know I've gotten dep you know some [13:28] people will relapse and need more [13:30] stimulation or need more psychedelics or [13:33] whatever it is but they'll tell me I [13:35] don't fear that I'm chronically broken. [13:37] I don't fear that the chemical imbalance [13:40] is still imbalanced. I don't fear that [13:42] these things that I couldn't control in [13:44] my childhood, you know, are going to be [13:46] there and drive this problem forever. [13:48] And I think that's that's what's so [13:50] powerful about this. [13:51] >> And that brings me to this uh question [13:53] about psychedelics and and the frankly [13:56] the altered thinking and perception that [13:58] occurs in in highdose psilocybin [14:02] clinical uh sessions. Many people do [14:04] report improvements in uh trauma related [14:07] symptomology and depression as I [14:09] understand it from my read of the [14:10] clinical trials after taking psilocybin [14:12] because during those sessions something [14:15] comes to mind spontaneously. They will [14:17] report, for instance, a new way of [14:19] seeing the old problem. That's right. [14:21] >> And the old problem could be the voice [14:22] that they're no good. They'll never [14:23] nothing will ever work out or could be [14:25] even more subtle than that. Why do you [14:27] think the brain would ever hold on to [14:30] rules that um uh don't serve us well? [14:33] >> I think it's an it's an it's an evol [14:36] evolutionary neurobiology answer, right? [14:39] I think that we end up being a result of [14:41] of probably a lot of biology that's not [14:43] that useful in the modern era. And I [14:45] think in the brain for for say let's say [14:48] PTSD, right? A lot of a lot of veterans [14:50] come back and they experience these PTSD [14:52] symptoms and they're not at all useful [14:54] back home, right? They hear some loud [14:56] noise and all of a sudden they're behind [14:58] a car or they're behind a you know I've [15:00] heard of folks you jump and run behind a [15:02] trash can or whatever in the middle of [15:04] San Francisco when they hear a loud [15:06] noise. But if you put them back in the [15:08] battlefield, [15:10] >> highly adaptive. [15:11] >> That's highly adaptive, right? We hold [15:12] on to those things from I think an [15:14] evolutionary neurobiology standpoint. [15:16] But what seems to for whatever reason [15:20] kind of alleviate that are these um are [15:24] these substances some new like MDMA, [15:27] some that have been around for thousands [15:29] of years like psilocybin seem to have a [15:33] therapeutic effect that seems to be [15:34] pretty longlasting for these phenomenon. [15:36] And so it's it's just curious, right? [15:39] It's curious that in the absence of that [15:41] these things will keep going on and on [15:43] but in the presence of that exposure [15:47] then all of a sudden you see a [15:49] resolution of the problem and we have [15:51] some work now we're treating folks with [15:52] Navy Seals the anecdotes that we're [15:54] getting right are folks are coming back [15:56] and they're saying these set of PTSD [15:58] symptoms are finally gone and so this [16:00] idea that for whatever reason going into [16:03] what's probably a highly plastic state [16:06] and reexperienced memories and then as [16:08] you you know, you know, we we [16:10] reconsolidating it in that state for [16:12] whatever reason um may drive um drive a [16:15] therapeutic effect. My business is to [16:18] find treatments that help people. And so [16:21] I'm much more like pragmatic about it. [16:23] You know, if if this sort of thing, [16:26] which um has a lot of cultural baggage, [16:30] um but if this sort of thing ultimately [16:32] ends up being therapeutic, if we can [16:33] design trials that convince me and [16:35] others that it is, then we should [16:37] absolutely use it. And if it doesn't, [16:39] then we clearly shouldn't use it, right? [16:40] The work that's been done so far, the [16:42] first psilocybin trial, um the first [16:45] MDMA trial that's published in nature [16:47] medicine recently. Um [16:48] >> and what do those generally say? Let's [16:50] let's uh start with psilocybin and MDMA. [16:53] So MDMA appears to in in um you know one [16:56] to a few MDMA sessions have an anti-PTSD [17:00] effect that seems to be you know um [17:03] outside of the kind of um standard [17:06] assumed levels of PTSD improvement that [17:08] you can observe in individuals um with [17:11] this level of PTSD. Right? So, [17:13] >> so does that mean that um for people [17:15] that have trauma who do a and again [17:17] we're talking about in a clinical [17:18] setting they they take a one or two [17:20] doses of of MDM I think the standard [17:23] MAPS dose is 150 to 175 milligrams again [17:26] doing this with a physician etc control [17:28] clinical trial legal [17:30] >> exactly [17:31] >> they do it once or twice and broadly [17:34] speaking what percentage of people who [17:36] had trauma report feeling significant [17:38] relief from their tra trauma afterward [17:41] >> it's about twothirds of people had a had [17:44] um a clinically significant uh change in [17:47] their PTSD. [17:48] >> That's impressive. And how how [17:49] longasting was that? [17:50] >> It appears to last for a while. In the [17:51] earlier trials where they followed [17:53] people out, it seemed to last for kind [17:54] of in the years range for some people. [17:56] And so it's, you know, it's pretty it's [17:58] pretty compelling. In contrast that with [18:00] ketamine, which only on average lasts [18:02] about a week and a half for a single [18:04] infusion. So it's a much shorter. [18:07] >> So they have to get repeated infusions [18:08] of ketamine every 10 days or so [18:11] >> for some people. or they end up getting [18:12] like like like a bunch of doses for a [18:15] couple of weeks and then for some people [18:17] that seems to last a while. Um you know [18:20] that's where I think I think the the [18:22] psilocybin story for depression and the [18:24] um in the MDMA story for PTSD seem more [18:26] interesting to me. [18:27] >> So for psilocybin what is the um rough [18:30] percentages on and this would be relief [18:32] not from trauma but from depression. [18:34] >> Yeah. Exactly. So it's, you know, in [18:36] open label studies, it's closer to like [18:38] half to 2/3 of people end up getting [18:40] better depending upon their level of [18:41] treatment resistance. In the in the [18:43] blinded trials, it was more like a third [18:45] or so of people. [18:46] >> Since you mentioned psilocybin, let's [18:48] talk a little bit about the [18:48] neurochemistry of psilocybin. What's [18:50] going on when one takes psilocybin and [18:52] um why is it interesting in light of [18:54] depression? [18:55] >> Yeah, definitely. So David Nut and Robin [18:57] Card Harris's work around neuroiming [19:00] psychedelics were kind of the some of [19:02] the first folks to do that work and um [19:04] you know and to their great surprise [19:06] they thought there was going to be an [19:07] increase in activity on psychedelics and [19:10] what they found is the opposite right [19:11] there's kind of a an overall decrease in [19:13] the level of activity in the brain um [19:16] with psychedelics but they they've also [19:18] looked at connectivity and there's this [19:20] kind of small world you know large world [19:23] connectivity that you you think about [19:25] and So you know small world meaning [19:27] there's a lot there's kind of a much [19:28] more kind of focused kind of cortical [19:30] function or you know subcortical [19:32] function or whatever it is and uh and [19:34] what you see is a difference in that um [19:38] in that level of engagement of of brain [19:40] regions the connectivity kind of global [19:42] connectivity kind of increases and so [19:45] it's interesting you know I think to to [19:48] kind of have a convergent theory on this [19:50] it's still you know to be determined [19:53] there's still a lot of work I think that [19:54] needs to be done. But um but it's [19:57] certainly um suggestive that there's [20:00] pretty profound changes in um in brain [20:03] activity and brain connectivity after. [20:06] And what we found to be really [20:07] interesting is the the anti-depressant [20:10] effects of psilocybin [20:13] have a particular um connectivity change [20:17] that we also see with our our TMS [20:19] approaches, right? And it's this [20:21] connectivity between the subgenial [20:23] anterior singulate and the default mode [20:25] network. And so when we do this [20:28] effective Stanford neurom modulation [20:30] therapy stimulation, we see a down [20:33] reggulation the connectivity between the [20:35] negatively valanced mood state in the [20:37] case of depressed individuals and the [20:38] self-representation of the brain. And [20:41] you see that same connectivity change [20:43] occur posts psilocybin, [20:46] you know, suggesting there's a [20:47] convergent mechanism. And it makes [20:49] sense, right? you've kind of got an [20:50] overconnected negatively balanced [20:53] system, conflict system that's kind of, [20:56] you know, kind of attached on to the [20:58] self-representation and people feel [21:00] stuck, right? And then when you when you [21:03] do whatever you do that's effective, it [21:04] it unpairs those two systems. [21:07] >> I want to ask you about Ibagane. Is it [21:10] legal in the US in terms as a clinical [21:13] tool? Who's using it and for what [21:15] purposes? Ibugane is a um is one of the [21:20] alkaloids that you can extract from a um [21:23] an ibogga tree root bark that's um [21:28] typically growing in the country of [21:31] Gabon Africa. So what uh individuals [21:34] taking ibeame will say is that open eyes [21:37] they don't see anything but closed eyes [21:39] they'll go back through and reexperience [21:42] earlier life memories and they will be [21:46] able to experience it from a place of [21:49] empathy not only for themselves but from [21:52] others and kind of a detached empathy [21:55] and being able to see this as almost a [21:58] third party even though they were there. [22:00] Ibegan is in no way a recreational [22:03] substance. You're essentially having [22:04] this what they call a life review. They [22:06] also call it 10 years of psychotherapy [22:08] in a night. So these are the terminology [22:11] that people talk about the issue. [22:12] >> How long does it last? Is it truly one [22:14] night [22:15] >> depending upon how fast you metabolize [22:17] it? Sometimes 24, sometimes 36 hours, [22:19] sometimes it can be shorter. But it is a [22:21] long time. [22:22] >> Wow. [22:22] >> It's a very long time. So it's it's [22:24] definitely the longest acting [22:26] psychedelic substance I know of. And so, [22:29] you know, we have over the last couple [22:31] of years been able to um to do this [22:35] first in human kind of full [22:37] neurobiological clinical neurocognitive [22:41] evaluation of what I is doing in this [22:45] case in in uh special operations, [22:47] special forces individuals, former Navy [22:49] Seals, former Army Rangers, that that [22:52] kind of crew of folks and look at the [22:54] pre-post changes that we um that they're [22:56] experiencing and be able to totally [22:58] quantitate all of that and so we've been [22:59] able to capture all the clinical scales [23:02] you know depression scales PTSD scales [23:04] all that standard stuff neurokcognitive [23:05] batteries so how does your executive [23:07] function work specifically how does your [23:09] verbal memory all of that and then neuro [23:12] imaging and EEG so this will be the [23:14] first human study of ibugane for those [23:17] and the reason why is because I gain [23:19] kind of the both seemingly the most [23:22] potent and most um [23:26] in and mo seemingly to me at least most [23:28] powerful um psychedelic, but the the one [23:31] that has the most risk too because it [23:33] has a cardiac effect. It seems to be [23:35] that you can screen people out that have [23:37] risk off of their electroc cardiogram [23:39] and and reduce the risk quite a bit and [23:41] that's what we we all did. But um but [23:44] but that's why people haven't really [23:45] studied it as much. Um and it's it isn't [23:48] as uh in addition there's nobody goes to [23:51] rave on ibain. There's no recreation at [23:53] all with it. [23:53] >> It's not fun. People say that it's [23:56] relieving, but it's hard work, right? [23:59] Because yeah, you're re you're [24:00] re-examining things. So then we see [24:03] these folks after and I I'll tell you, [24:04] you know, we haven't fully analyze the [24:06] data yet, but I'll tell you that from [24:08] what my folks are telling me, it's [24:10] pretty dramatic. You know, people come [24:11] back and they're doing a lot better. [24:13] Soldiers experience something called [24:15] moral injury, right? Where they maybe [24:17] they accidentally blew something up and [24:19] it had a kid in it or something like [24:21] that. you know, you know, if they're in [24:23] Afghanistan or Iraq, maybe, you know, a [24:25] child died on accident or maybe maybe, [24:27] you know, a civilian died or whatever it [24:29] was, right? And they and they suffer [24:31] these moral injuries as part of the job. [24:33] And it's almost one of the kind of, you [24:34] know, vocational risks. They come back [24:37] and say that they've they've they've um [24:39] forgiven themselves, you know, which is [24:41] which is huge, right? And and part of [24:43] that is being able to see themsel in a [24:46] different light and having empathy [24:47] finally for themsel and being able to [24:49] kind of have that experience of [24:51] forgiving. And so there's this kind of [24:53] Timothy Liry kind of socioultural [24:55] construct that ends up being overlaid [24:57] over psychedelics. And what I think is [25:01] that if you rid yourself of all of those [25:05] preconceived notions of what it is and [25:08] isn't and the counterculture movement, [25:09] all that stuff that neither of us were [25:11] ever involved in, neither of us are ever [25:13] partake in, you know, as is kind of [25:15] straight scientists looking at this, [25:16] right? If you can kind of rid yourself [25:18] of all those socioultural constructions [25:20] and then re-examine this, these if we [25:23] just discovered these today, we would [25:26] say that these sorts of drugs are a huge [25:29] breakthrough in psychiatry because they [25:31] allow for us to do a lot of the sorts of [25:33] things we've been thinking about with [25:35] with SSRIs, with psychotherapy, but kind [25:38] of combined, right? psychotherapy plus [25:41] plus plus drugs in a in a substance that [25:44] kind of allows you to reexamine these [25:47] things. And so it's it's interesting. [25:48] It'll you know there's a lot to do to [25:50] try to figure out if that's true, you [25:53] know, and and I can say that as it [25:55] stands right now, we don't know if it's [25:57] that statement is true, right? There's a [25:59] lot more work that needs to happen for [26:01] that statement to be proven to be true. [26:03] But the hypothesis is if it is true then [26:06] it's very likely that [26:09] this will be seen as a breakthrough [26:11] because it allows you to do these sorts [26:13] of things that you can't do with normal [26:15] waking consciousness. [26:17] But also why we have to really think [26:20] about this and you know these drugs [26:23] can't be recreational drugs. They really [26:26] shouldn't be recreational drugs, right? [26:29] they're really too powerful to be used [26:32] in the context of recreation because [26:35] they can put you into these states and [26:37] and the this generation of psychedelic [26:40] researchers are really clear about that. [26:42] You know, I think the ' 60s folks were [26:44] not clear about that and they they felt [26:46] like there was this whole kind of [26:48] cultural thing that was going on there. [26:50] But I think this cohort of individuals [26:52] really understands that in order to [26:55] really make this happen, we have to [26:57] understand that if you need a [26:58] prescription for an SSRI, which doesn't [27:02] change your consciousness a whole lot, [27:04] and we we're very worried about that and [27:06] the doctor has to evaluate you for that [27:08] every week, that the idea that some of [27:10] these substances would would go outside [27:12] of of very strict medical supervision is [27:15] uh is kind of preposterous, actually. [27:18] It's kind of it's kind of a a dumb [27:20] moment, I think, for for all of medicine [27:22] to say, "Look, we've, you know, if we're [27:24] going to do this right, we've got to do [27:25] it in such a way that's so protected, [27:27] that's so safe that we make sure people [27:30] know these things are not recreational, [27:32] and they're really for the pure purposes [27:35] of of really powerfully changing um [27:38] cognition for a while and letting people [27:40] have these what seem to be, you know, [27:42] relatively therapeutic states. Tell me [27:44] about Iawaska um and as a plant. Is it [27:49] useful for the same sorts of conditions [27:51] that we've talked about um thus far? And [27:53] if you could um perhaps tell me a little [27:55] bit also about the um Brazilian prisoner [27:57] study. [27:58] >> Yeah, [27:59] >> definitely. IA is another psychedelic. [28:01] It's used as a sacrament um in um in [28:05] Brazil and um in Peru and Ecuador and [28:08] Colombia. So a lot of the South American [28:11] countries and um and what they do is [28:14] they combine two plants together where [28:18] one plant of the two plant combination [28:21] would effectively do nothing but the two [28:24] plant combination together is capable of [28:27] producing this very profound psychedelic [28:29] effect. And what's really kind of [28:32] curious is that there are, as I [28:35] understand it, 10 to 20,000 plant [28:38] species in the Amazon. And somehow [28:41] somebody [28:42] >> someone tried them all [28:43] >> combined these two plants together in [28:46] certain proportionality [28:48] and cooked this for five 10 hours to the [28:51] point where you cook out the [28:53] dimethylryptamine out of one of the [28:54] plants and cook out the reversible [28:57] monoamine oxidase inhibitor out of the [28:59] other plant. It's such a way that the [29:03] reversible monoamine oxidase inhibitor [29:05] prevents the the GI breakdown of the [29:08] dimethylrypamine in such a way that it's [29:10] then allowed to cross the bloodb brain [29:13] barrier and get into the brain. And if [29:15] you didn't add the reversible monomine [29:17] oxidase inhibitor plantder derived into [29:20] this combination then it would never [29:22] cross the brain. If you put people on a [29:26] standard psychiatry prescribed [29:28] monoimmune oxidase inhibitor that wasn't [29:30] reversible, you'd throw them into [29:32] serotonin syndrome. Right? So this kind [29:34] of like sweet spot that somehow I [29:39] practitioners have found of being able [29:41] to get DMT into the brain from an oral [29:44] source with this combination of a [29:46] monomine oxidase inhibitor. It's [29:49] curious. Um and so that that substance [29:52] has been explored as an anti-depressant [29:54] agent and some studies have looked at [29:57] that. It also seems to be very safe [29:59] there. Um there was a there's a [30:00] psychiatrist down at um UCLA Harbor [30:04] who's done a lot of work with this where [30:06] um where he's looked at children even [30:08] that have been exposed to to kind of [30:10] small doses of Iawaska as is kind of a [30:13] sacrament within Amazonian tribes and [30:16] found no neurocognitive effects, no [30:17] neurocognitive effects in adults. And so [30:20] it appears to be safe. It's kind of part [30:22] and brought into various religions [30:25] including kind of merged with [30:26] Catholicism in South America which is [30:28] kind of very interesting. And so you [30:31] know in some [30:33] sects of Catholicism in Brazil it's used [30:37] as a sacrament during religious um [30:40] ceremonies. And so it became interesting [30:43] to Brazilian researchers as to whether [30:46] or not they could affect recidivism [30:48] rates for prisoners in Brazilian [30:51] prisons, right? So they gave half of the [30:53] prisoners [30:55] um you know some sort of inert substance [30:57] and half of the prisoners a um an [31:00] Iawaska session. And the the uh [31:03] recidivism rate or the return to prison [31:05] rate in the Iawaska exposed individuals [31:08] was statistically significantly lower [31:10] than the recidivism rate in the uh in [31:12] the control group. suggesting that um [31:15] you know whatever is going on there [31:18] seems to have an effect on whatever [31:20] drives criminal behavior whatever [31:22] criminal behavior that happened to be [31:24] and I don't have the the details on the [31:26] exact nature of the crime. Um you know [31:29] no I am also in no way saying that we [31:31] should just be giving psychedelics to to [31:32] to folks in prison and all of that. I [31:35] think that that that that is a very edgy [31:38] thing to do and probably not something [31:40] that anybody should try. But but it does [31:42] it does kind of bring up this this [31:44] curious question of of what is it about [31:47] that that would drive people to um to [31:50] change those behaviors and and why why [31:52] do people make those behavioral [31:54] decisions? [31:54] >> Before we wrap, I do want to give you [31:57] the opportunity to talk about the Saint [31:58] study. [31:59] >> Yeah. Saint or what we're we're calling [32:01] it S&T now. Um Stanford accelerated [32:04] intelligent neurom modulation therapy or [32:06] now what we're calling Stanford neurom [32:07] modulation therapy. The idea there is [32:09] that TMS um is a device that delivers um [32:14] that delivers a treatment and the [32:17] treatment is the protocol and the [32:19] protocol is the stimulation parameter [32:23] set in a specific brain region for a [32:26] specific condition. Whether it be [32:28] transcranial magnetic stimulation or [32:30] transcranial direct current stimulation [32:31] or deep brain stimulation like what [32:33] Casey Halpern talked about. In all of [32:35] those cases, the device itself is a [32:38] physical layer conduit of a stimulation [32:41] protocol that's therapeutic for a given [32:44] condition in a given brain region. We [32:46] decided gosh, you know, this problem I [32:48] talked about at the beginning of the [32:49] show where you have these, you know, [32:51] this problem that we we don't have a [32:53] treatment for people who are in these [32:55] high acuity psychiatric emergency [32:58] states, right? this idea that we're [33:00] going to engineer a treatment where we [33:02] can reorganize the stimulation approach [33:04] in time to be much more efficient by [33:08] utilizing something called space [33:09] learning theory. And so you you probably [33:11] know about the space learning theory. So [33:12] the idea for the for the viewers is if [33:14] I'm cramming for a test, what I do is I [33:17] write out 60 note cards and I read each [33:20] one for a minute until I get to the [33:21] first note card and again and that's [33:23] about an hour later, right? That's space [33:25] learning theory. It's this idea that you [33:26] need to see it about every hour to an [33:28] hour and a half and that optimizes [33:30] learning. What we found was is that the [33:32] old way of doing TMS, this idea of just [33:34] doing it once a day, every day, 5 days a [33:37] week for 6 weeks, didn't utilize the [33:39] space learning theory. It's like [33:41] studying for a month or two, just a [33:44] little bit once a day. Like you remember [33:46] some of that stuff, but it's like not as [33:47] potent as that week where you're kind of [33:49] cramming, right? And what we realized is [33:51] that if we could reorganize the [33:54] stimulation in times that we took the [33:55] whole six week course, we actually [33:57] figured out a way to do it in a day. And [33:59] then what we also figured out is that [34:00] people were underdosing TMS because if [34:03] you just keep going after 6 weeks out to [34:05] month three, four, five, more and more [34:07] people got better. So we figured out [34:09] it's not just one day. We're going to [34:10] give five times the normal dose. We're [34:12] going to give 7 and 1/2 months worth in [34:13] 5 days using space learning theory. So [34:17] every hour [34:18] >> every hour for 10 hours [34:19] >> for 5 days [34:20] >> for 5 days. So it's a 50-hour block. [34:22] It's 90 minutes of actual stimulation [34:25] but spread out through the day in the [34:26] same way of learning. What we've found [34:28] is that folks will um will within one to [34:32] five days, you know, in in more cases [34:35] than not, depending upon if you're [34:36] looking at this open label or in trials, [34:38] somewhere between 60 and 90% of the [34:41] time, they will go into full-on [34:43] remission in the sense they're totally [34:46] normal from a mood standpoint at the end [34:48] of this. And like I said, with variable [34:50] dur durability. So that's the part we [34:52] have to figure out now about dosing and [34:53] how to keep people well. But for some [34:55] people, you know, we've had four years [34:56] of remission, you know, a year of [34:58] remission. And it's it's really that [35:00] cramming of the test. It's really that [35:02] idea that you're laying in that [35:05] information to the exact right spot. And [35:08] the the signal is a simple signal, but [35:09] it's a profound one, which is turn on, [35:13] stay on, remember to stay on. You know [35:16] that idea that you're si you're sending [35:18] this memory signal into the brain and [35:20] you're doing it in such a way that [35:21] you're telling the system you're kind of [35:23] taking it out of the hippocampus's hand [35:25] your own hippocampus' hand and you're [35:27] sending the same signal the hippocampus [35:29] normally signals out. Now you're sending [35:31] that signal into the prefrontal cortex [35:34] and kind of utilizing the brain's own [35:37] communication style to get it to get out [35:40] of this state. And what's very cool [35:43] about this is that um is that people [35:45] when they when they kind of exit out of [35:47] that, they end up um they end up saying [35:51] they don't have any any side effects [35:52] from it and they feel back to normal. [35:56] >> Thank you so much uh for taking us on [36:00] this incredible voyage through the [36:02] neurosircuitry underlying certain [36:05] aspects of depression, the coverage of [36:06] the different types of depression, the [36:08] various uh therapeutic compounds, how [36:10] they work. We've um talked about a lot [36:12] of things today and you you've shared so [36:14] much knowledge and even as I say that I [36:16] um I very much want to have you back to [36:18] talk about many other things as well [36:20] that we didn't have time to cover. But [36:22] to take the time to sit down with us and [36:23] share all this knowledge that really is [36:25] in service to mental health and and [36:28] human feeling better and in fact [36:31] avoiding often suicidal depression. It's [36:33] just incredible work and an incredible [36:35] generosity and just thank you so much. [36:38] >> Absolutely. Thank you. [36:40] >> [music]