Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity

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. Use Ask Huberman Lab, our new AI-powered platform, for a summary, clips, and insights from this episode. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/huberman Waking Up: https://wakingup.com/huberman Momentous: https://www.livemomentous.com/huberman 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 Disclaimer