Episode 31 - The Clinician’s Guide to Ketamine Therapy: History, Science & Real-World Protocols

Understand the evolution, mechanisms, and clinical use of ketamine therapy for depression, PTSD, anxiety, and chronic pain—with protocols, science, and real-world insights for medical professionals.

In this episode, Sam presents a comprehensive overview of ketamine therapy from a clinical lens. Originally delivered as a lecture titled “Exploring Ketamine IV Infusions: A Novel Approach for Depression, PTSD, Anxiety, & Chronic Pain” to the UCLA–Betty Ford Addiction Medicine Fellowship, this session walks through everything from the mental health crisis to ketamine’s evolving role in modern treatment.

Whether you’re a curious clinician or an experienced provider, this is your go-to primer on how ketamine therapy works—and why it matters now more than ever. With over 50 years of clinical use and a growing body of scientific research, ketamine is proving to be a powerful option for treatment-resistant depression, PTSD, anxiety, and chronic pain. 

Sam brings together the science, protocols, and personal insights from running a real-world ketamine clinic to help demystify the treatment process and spark deeper understanding among medical professionals.

What You'll Learn in This Episode:

  • A deeper understanding of how ketamine works in the brain

  • Knowledge of current research and studies supporting ketamine’s use

  • Insights into patient selection, safety, and personalized dosing strategies

Listen to the episode on Apple Podcasts, Spotify, Overcast, or on your favorite podcast platform. Watch the discussion on YouTube here.

Episode 31 show notes:

  • 00:00 Teaser - Depression is the leading cause of disability worldwide.

  • 00:30 Welcome and Episode Overview

  • 01:17 Ketamine Infusions: A Novel Approach

  • 02:17 Current State of Mental Health and Ketamine History

  • 09:36 Mechanisms of Action and Scientific Studies

  • 12:11 Patient Experiences and Clinical Applications

  • 23:22 Ideal Patient Selection and Dosing Protocols

  • 29:10 Potential Side Effects and Addiction Risks

  • 33:21 Conclusion and Final Thoughts

Thanks for listening!

  • “Depressive Disorder (Depression).” World Health Organization, World Health Organization, www.who.int/news-room/fact-sheets/detail/depression. Accessed 25 Sept. 2024. 

    Forster, Peter. “Default Mode Network and Depression Treatment - Ketamine and TMS.” Gateway Psychiatric, 24 June 2021, www.gatewaypsychiatric.com/default-mode-network-and-depression/

    Kolp, Eli & L. Friedman, Harris & Krupitsky, Evgeny & Jansen, Karl & Sylvester, Mark & Young, Matthew & Kolp, Anna. (2014). Ketamine Psychedelic Psychotherapy: Focus on its Pharmacology, Phenomenology, and Clinical Applications. International Journal of Transpersonal Studies. 33. 84-140. 10.24972/ijts.2014.33.2.84.

    Depression:

    • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9. PMID: 10686270.

    • Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, Beauchamp S. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019. J Affect Disord. 2020 Dec 1;277:831-841. doi: 10.1016/j.jad.2020.09.007. Epub 2020 Sep 7. PMID: 33065824.

    • Anand A, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Altinay M, Aloysi AS, Asghar-Ali AA, Barnett BS, Chang LC, Collins KA, Costi S, Iqbal S, Jha MK, Krishnan K, Malone DA, Nikayin S, Nissen SE, Ostroff RB, Reti IM, Wilkinson ST, Wolski K, Hu B. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med. 2023 Jun 22;388(25):2315-2325. doi: 10.1056/NEJMoa2302399. Epub 2023 May 24. PMID: 37224232.

    • Jha MK, Wilkinson ST, Krishnan K, Collins KA, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Costi S, Malone D, Nikayin S, Nissen SE, Ostroff R, Reti I, Wolski K, Wang D, Hu B, Mathew SJ, Anand A. Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2417786. doi: 10.1001/jamanetworkopen.2024.17786. PMID: 38916891; PMCID: PMC11200139.

    Anxiety:

    • Glue P, Medlicott NJ, Harland S, Neehoff S, Anderson-Fahey B, Le Nedelec M, Gray A, McNaughton N. Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. J Psychopharmacol. 2017 Oct;31(10):1302-1305. doi: 10.1177/0269881117705089. Epub 2017 Apr 26. PMID: 28441895.

    PTSD:

    • Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62. PMID: 24740528.

    • Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021 Feb 1;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596. Epub 2021 Jan 5. PMID: 33397139.

    Chronic Pain:

    • Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesth Analg. 2019 Jul;129(1):241-254. doi: 10.1213/ANE.0000000000004185. PMID: 31082965.

    Addiction:

    • Active/Lethal Dose Ratio and Dependence Potential of Psychoactive Drugs. Data source is Gable, R. S. (2006). Acute toxicity of drugs versus regulatory status. In J. M. Fish (Ed.),Drugs and Society: U.S. Public Policy, pp.149-162, Lanham, MD: Rowman & Littlefield Publishers.

    Substance Use Disorder:

    • Jones JL, Mateus CF, Malcolm RJ, Brady KT, Back SE. Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review. Front Psychiatry. 2018 Jul 24;9:277. doi: 10.3389/fpsyt.2018.00277. PMID: 30140240; PMCID: PMC6094990.


    Alcohol Use Disorder:

 
Next
Next

Episode 30 - When Is the Right Time to Go Full-Time with Your Ketamine Clinic?