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. #HubermanLab #Science Thank you to our sponsors AG1: https://drinkag1.com/huberman ROKA: https://roka.com/huberman Eight Sleep: https://eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Social & Website Instagram: https://www.instagram.com/hubermanlab Threads: https://www.threads.net/@hubermanlab Twitter: https://twitter.com/hubermanlab Facebook: https://www.facebook.com/hubermanlab TikTok: https://www.tiktok.com/@hubermanlab LinkedIn: https://www.linkedin.com/in/andrew-huberman Website: https://hubermanlab.com Newsletter: https://hubermanlab.com/neural-network 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