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Research by Dr. Thomas Swahn

A deeper look at the ketamine molecule

Man Looking Up At the Sun

Barriers to Using Ketamine for the Treatment of Depression

Mark Beebe, Sara Maestas, and Thomas K. Swahn

Depressive disorders are prevalent in the United States. Current treatment paradigms take weeks to reach clinical efficacy and may leave patients at risk for suicide during the initial weeks of treatment. Intravenous (IV) ketamine infusions have shown promise in the rapid relief of depression symptoms, including efficacy in treatment-resistant depression and relief of suicidal ideation. Initial research has shown ketamine therapy to be safe and effective. Despite a plethora of information in support of the safety and efficacy of ketamine, there is reluctance of both patient and provider in utilizing ketamine’s unique potential. We used a grounded-theory approach to perform a meta-analysis literature review exploring the barriers preventing widespread acceptance of ketamine therapy. We found fear or moral objection to psychoactive effects, potential side effects, and history of abuse as a street drug to be inhibiting factors among patients. Among healthcare providers, barriers included lack of accessibility, addictiveness, abuse potential, and refusal of insurance policies to cover treatment. We present arguments to challenge objections and question concerns as the vast benefit of ketamine therapy far outweighs potential harms. We give recommendations for further research and call for a more rational approach to U.S. drug policy with a focus on objective evidence and an elimination of unwarranted restriction of personal freedoms.

Books We Recommend

Effect of Education on Perception of Ketamine in Primary Care and Mental Health Providers

Thomas K. Swahn, MSN, APRN, FNP-C, DNP-Student Project Chair: Julie Balk, DNP, APRN, FNP-C Content Expert: Eric C. Welling, MD, MBA

Background: Mental illness is a major healthcare problem. In the United States, 21% of adults are afflicted by a mental illness. Ketamine therapy is a promising treatment for many mood disorders including treatment-resistant depression, yet is underutilized in US healthcare. Purpose: This project aimed to explore the perspectives of primary care providers and mental health providers toward ketamine therapy. Implementation: Surveys and an educational presentation were developed to identify providers’ perspectives of ketamine therapy before and after education. These were distributed to primary care practices and mental health practices from the 84015 ZIP code and surrounding areas. The surveys included open-ended qualitative questions and quantitative questions using Likert scales to evaluate views. Results: A small number of providers participated, limiting generalizability of results. Statistical analysis was performed to evaluate changes in quantitative responses, finding an increased rating of familiarity with ketamine and its psychoactive effects, as well as increased perception of safety, though there was a decreased likelihood to recommend ketamine therapy for patients or to utilize for themselves or loved ones among medical providers. Qualitative analysis was done in an iterative review revealing themes associated with ketamine in participants perspectives, with medical terminology comprising the bulk of initial perspectives and shifting post-education responses toward different themes. Discussion: The findings of this study suggest that medical providers may be less inclined to recommend ketamine therapy after education discussing its psychoactive effects despite evidence of its efficacy, whereas mental health providers show much more openness to both aspects. Future research should aim to clarify factors influencing this discrepancy and to develop more effective educational approaches.

Ketamine Educational Presentation by Thomas Swahn (Length: 9:44)
April 18, 2022

Introductory education on ketamine therapy, created as part of Thomas Swahn's Doctoral Scholarly Project.

Articles & News

NOVA: Can Psychedelics Cure?

Hallucinogenic drugs—popularly called psychedelics—have been used by human societies for thousands of years. Today, scientists are taking a second look at many of these mind-altering substances – both natural and synthetic – and discovering that they can have profoundly positive clinical impacts, helping patients struggling with a range of afflictions from addiction to depression and PTSD.

Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity | Huberman Lab Podcast
01:42:41

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. #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

Academic Literature

Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis.

Bahji, A., Vazquez, G. H., & Zarate, C. A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 278, 542–555

Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy

Dore, J., Turnipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., Monnette, C., Huidekoper, A., Strauss, N., & Wolfson, P. (2019). Ketamine assisted psychotherapy (KAP): Patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. Journal of Psychoactive Drugs, 51(2), 189-198.

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial

Dwyer, J. B., Landeros-Weisenberger, A., Johnson, J. A., Londono Tobon, A., Flores, J. M., Nasir, M., Couloures, K., Sanacora, G., & Bloch, M. H. (2021). Efficacy of intravenous ketamine in adolescent treatment-resistant depression: A randomized midazolam-controlled trial. The American Journal of Psychiatry, 178(4), 352–362.

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder

Feder, A., Costi, S., Rutter, S. B., Collins, A. B., Govindarajulu, U., Jha, M. K., Horn, S. R., Kautz, M., Corniquel, M., Collins, K. A., Bevilacqua, L., Glasgow, A. M., Brallier, J., Pietrzak, R. H., Murrough, J. W., & Charney, D. S. (2021). A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. The American Journal of Psychiatry, 178(2), 193–202.

Safety of Repeated Administration of Parenteral Ketamine for Depression

Feifel D, Dadiomov D, C. Lee K. (2020). Safety of repeated administration of parenteral ketamine for depression. Pharmaceuticals, 13(7),151.

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020). Integrating psychotherapy and psychopharmacology: Psychedelic-assisted psychotherapy and other combined treatments. Expert Review of Clinical Pharmacology, 13(6), 655–670.

A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders

Kim, S., Rush, B.S. & Rice, T.R. (2020). A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders. European Journal of Child & Adolescent Psychiatry.

Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review

Mathai, D., Mathew, S. J., Storch, E. A., & Kosten, T. R. (2018). Revisiting the hallucinogenic potential of ketamine. Psychiatric Times, 35(6).

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders

Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., Summergrad, P., & Nemeroff, C. B. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399-405. 

Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2017). Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression. Psychotherapy and Psychosomatics, 86(3), 162–167.

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