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.

Articles

• Antidepressant effects of ketamine in depressed patients (Biological Psychiatry)
• Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism (Molecular Psychiatry)
• atai Life Sciences Announces Results from Phase 2a Trial of PCN-101 (R-ketamine) for Treatment-Resistant Depression
• Comparative effects of (S)-ketamine and racemic (R/S)-ketamine on psychopathology, state of consciousness and neurocognitive performance in healthy volunteers (European Neuropsychopharmacology)
• Ketamine Metabolite (2R,6R)-Hydroxynorketamine Interacts with μ and κ Opioid Receptors (ACS Chemical Neuroscience)
• Ketamine: 50 Years of Modulating the Mind (Frontiers in Human Neuroscience)
• Chapter 7 - The Monoamine Hypothesis of Depression Revisited: Could It Mechanistically Novel Antidepressant Strategies? (Neurobiology of Depression)
• Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression (Behavioural Brain Research)
• A historical review of antidepressant effects of ketamine and its enantiomers (Pharmacology Biochemistry and Behavior)
• Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression (The New England Journal of Medicine)
• Antidepressant effects of ketamine in depressed patients (Biological Psychiatry)
• NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses (Nature)
• Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients (Biological Psychiatry)
• Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism (Molecular Psychiatry)
• Ketamine blocks bursting in the lateral habenula to rapidly relieve depression (Nature)
• Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology (Nature Communications)
• A Double-Blind, Placebo-Controlled Study of Memantine in the Treatment of Major Depression (The American Journal of Psychiatry)
• Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study (Journal of Affective Disorders)
• Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis (Journal of Affective Disorders)

Huberman Lab Episodes Mentioned

• The Science & Treatment of Bipolar Disorder
• How Psilocybin Can Rewire Our Brain, Its Therapeutic Benefits & Its Risks
• MDMA & PTSD relief (timestamp)