Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast

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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Articles
Antidepressant effects of ketamine in depressed patients: https://bit.ly/44YTGxY
Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism: https://go.nature.com/3qesrR8
atai Life Sciences Announces Results from Phase 2a Trial of PCN-101 (R-ketamine) for Treatment-Resistant Depression: https://bit.ly/47j6wsC
Comparative effects of (S)-ketamine and racemic (R/S)-ketamine on psychopathology, state of consciousness and neurocognitive performance in healthy volunteers: https://bit.ly/44WMxOR
Ketamine Metabolite (2R,6R)-Hydroxynorketamine Interacts with μ and κ Opioid Receptors: https://bit.ly/44e4SWB

Other Resources
The Science & Treatment of Bipolar Disorder (Huberman Lab episode): https://hubermanlab.com/the-science-and-treatment-of-bipolar-disorder/

Timestamps
00:00:00 Ketamine
00:02:29 Sponsors: ROKA & Eight Sleep
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
00:33:24 Sponsor: AG1
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
01:02:28 Sponsor: LMNT
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

The Huberman Lab podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast or materials linked from this podcast is at the user’s own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their health care professionals for any such conditions.

Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com