本期节目深入探讨了氯胺酮如何通过重塑大脑回路和解离状态来缓解抑郁症和创伤后应激障碍（PTSD）的症状。节目解释了氯胺酮如何影响大脑的谷氨酸和内源性阿片类物质通路，这些通路共同调节情绪和幸福感。节目还讨论了氯胺酮疗法在临床上治疗重度抑郁症、双相抑郁症、强迫症（OCD）、自杀倾向和其他精神健康挑战中的应用。此外，节目还描述了氯胺酮如何引起解离和欣快的主观感受，以及在更高剂量下如何作为麻醉剂。节目比较了氯胺酮的不同给药途径、剂量和形式，并探讨了微剂量氯胺酮是否有效。节目还强调了娱乐性氯胺酮使用（以及俗称的“K-洞”）的潜在风险。

🎯 氯胺酮通过影响大脑的谷氨酸和内源性阿片类物质通路，重塑大脑回路并产生解离状态，从而缓解抑郁症和创伤后应激障碍（PTSD）的症状。氯胺酮通过影响NMDA受体，增加神经可塑性，促进新的神经连接的形成，从而帮助大脑重新适应压力和创伤的影响。

🧠 氯胺酮在临床上被用于治疗多种精神健康挑战，包括重度抑郁症、双相抑郁症、强迫症（OCD）、自杀倾向等。氯胺酮疗法通常以静脉注射或鼻腔喷雾的方式进行，并已显示出快速改善情绪和减少自杀风险的积极效果。

💊 氯胺酮的治疗机制涉及多个神经通路。氯胺酮通过阻断NMDA受体，增加谷氨酸的释放，并激活内源性阿片类物质系统，从而产生抗抑郁和抗焦虑的效果。氯胺酮还能够促进脑源性神经营养因子（BDNF）的释放，BDNF是一种对神经元生长和存活至关重要的蛋白质，其水平在抑郁症患者中往往较低。

⚠️ 虽然氯胺酮在治疗精神疾病方面显示出巨大潜力，但它也存在潜在的风险。娱乐性氯胺酮使用可能导致解离、幻觉、认知障碍和心脏问题。因此，在医生的指导下使用氯胺酮至关重要。

💡 氯胺酮的治疗效果可能因个体差异而异，且其长期效果尚待进一步研究。尽管如此，氯胺酮疗法为治疗抑郁症和创伤后应激障碍提供了新的希望，并为我们理解大脑的可塑性和精神疾病的治疗提供了宝贵的见解。

In this episode, I explain how ketamine causes rewiring of brain circuits and dissociative states to relieve symptoms of depression and post-traumatic stress disorder (PTSD). I explain how ketamine impacts both the brain’s glutamate and its endogenous opioid pathways, which together regulate mood and well-being. I discuss how ketamine therapy is used clinically to treat major depression, bipolar depression, obsessive-compulsive disorder (OCD), suicidality and other psychiatric challenges. I also describe how ketamine causes the subjective effects of dissociation and euphoria and, at higher doses, is an anesthetic. I compare the different routes of ketamine administration, dosages and forms of ketamine, and if micro-dosing ketamine is effective. I also highlight the potential risks of recreational ketamine use (and the colloquial term ‘K-holes’). This episode should interest anyone interested in ketamine, treatments for depression, neuroplasticity mechanisms, psychiatry and mental health.

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Timestamps

(00:00:00) Ketamine

(00:02:46) Sponsors: LMNT & Waking Up

(00:05:13) Ketamine & PCP; Clinical & Recreational Use

(00:09:00) Depression & Current Treatments

(00:15:17) Preclinical Models of Depression & Ketamine; “Learned Helplessness” 

(00:22:11) Ketamine & Clinical Uses; Depression & Suicidality 

(00:28:32) Ketamine & Other Psychiatric Challenges; Relief & Durability 

(00:33:40) Sponsor: AG1 (Athletic Greens)

(00:34:29) NMDA Receptor & Neuroplasticity

(00:41:36) Excitatory & Inhibitory Communication, Seizure, NMDA Receptors & Ketamine

(00:48:26) How Ketamine Functions in Brain; Acute & Long-Term Effects

(00:55:36) Brain-Derived Neurotrophic Factor (BDNF) & Ketamine Therapy

(01:03:40) Ketamine & Opioid Pathway 

(01:10:00) Divergent Mechanisms of Immediate & Long-Term Effects

(01:15:45) Habenula, Pro-Depressive Behaviors & Ketamine Therapy

(01:20:36) Ketamine & Context-Dependent Strategy; Reward Pathway

(01:22:45) Dissociative States

(01:26:04) Doses & Routes of Administration; “K-holes”; Risk & Caution

(01:32:25) Ketamine Forms; R-, S- vs R/S- Ketamine; Micro-Dosing

(01:38:24) Ketamine: Effects & Therapy

(01:40:40) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter

Title Card Photo Credit: Mike Blabac

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