Huberman Lab

Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity

Aug 7, 2023

Explore how ketamine rewires brain circuits to alleviate depression and PTSD. Learn about its effects on glutamate and opioid pathways that influence mood. Discover its rapid antidepressant properties and the different administration methods available. Delve into the risks of recreational use, including the infamous 'K-holes.' The episode highlights ketamine's evolution from street drug to clinical treatment, while questioning the effectiveness of traditional antidepressants in comparison.

01:39:56

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Quick takeaways

Ketamine has clinical benefits for treating depression, suicidality, and PTSD, but recreational use poses risks and potential for abuse.

Ketamine increases neuroplasticity in brain circuits involved in mood and reward, despite being an NMDA receptor blocker.

Repeated treatments of ketamine provide rapid relief from depression, with effects lasting for several days.

Ketamine's impacts on neural circuits involved in mood regulation include weakening connections between the habenula and reward pathways, and strengthening connectivity between the reward pathway and frontal cortex.

Deep dives

Ketamine's Clinical Benefits and Risks

Ketamine is a compound used both clinically and recreationally, with clinical benefits including treatment for depression, suicidality, and PTSD. However, there are also risks and potential for abuse associated with its recreational use. The podcast explores the research on the clinical benefits of ketamine, the mechanisms behind its dissociative states, dosage and delivery routes, and emphasizes both the benefits and risks of ketamine use.

The Link Between Lack of Sleep and Depression

01:27

S and 90s: The Monoamine Hypothesis of Depression

00:50

Ketamine Dosage Regimens and Relief from Depression

01:56

The Effects of Ketamine on the Brain's Reward Pathway

02:28

Intro

4min

Morning Habits and Sleep Optimization: The Role of Ketamine

2min

Evolving Perspectives on Ketamine: From Street Drug to Clinical Treatment

4min

Exploring Monoamines and Ketamine's Role in Depression Treatment

12min

Ketamine and Rapid Antidepressant Effects

1h 21min

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.

For show notes, including referenced articles and additional resources, please visit hubermanlab.com.

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Thank you to our sponsors

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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

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Huberman Lab

Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity

Podcast summary created with Snipd AI

Quick takeaways

Deep dives

Ketamine's Clinical Benefits and Risks

Ketamine and Neuroplasticity

Ketamine's Short-Term and Long-Term Effects on Depression

The Paradoxical Effects of Ketamine

Ketamine's Impact on Neural Circuits and Neuroplasticity

The Role of Opioid Receptors in Ketamine's Effects

Neural Circuits Affected by Ketamine

Dosage, Forms, and Considerations

The Link Between Lack of Sleep and Depression

S and 90s: The Monoamine Hypothesis of Depression

Ketamine Dosage Regimens and Relief from Depression

The Effects of Ketamine on the Brain's Reward Pathway

Timestamps

Remember Everything You Learn from Podcasts