Ketamine was initially developed as a surgical anesthetic in the 1960s, and shortly thereafter found use as a field anesthetic in the Vietnam War. Over the ensuing decades, it was deemed a WHO Essential Medicine, providing effective anesthesia, analgesia and sedation in clinics and hospitals around the world. In recent years, however, there has been an explosion of interest in using ketamine for mental health conditions, psychotherapeutic work and psycho-spiritual exploration.
Notably, on the psychiatric front, the FDA approved the first ketamine-related treatment in 2019 for severe depression, and racemic ketamine continues to be successfully used off-label for depression and other disorders across hundreds of legal clinics around the country. While antidepressants work for some, many others find no relief. Accordingly, a booming psychedelic ketamine industry has sprung up. Ketamine for depression has ushered in a new paradigm for treatment-resistant depression. This article contains ketamine resources for those interested in learning more about the drug and treatment, covering recreational ketamine use, ketamine infusion therapy, and ketamine-assisted psychotherapy.
Reality Sandwich Articles on Ketamine
Below is a list of articles centered around ketamine that have been published on Reality Sandwich since 2016:
- Ketamine Guide: Effects, Common Uses, Safety
- Microdosing Ketamine & Common Dosages Explained
- How Ketamine is Made: Everything You Need to Know
- Guide to Ketamine Treatments: Understanding the New Approach
- Types of Ketamine: Learn the Differences & Uses for Each
- How to Buy Ketamine: Is there Legal Ketamine Online?
- Ketamine for Depression: A Mental Health Breakthrough
- Having Sex on Ketamine: Getting Physical on a Dissociative
- How to Ease a Ketamine Comedown
- Kitty Flipping: When Ketamine and Molly Meet
- The Veterans’ Experience: Psychedelic Treatments for PTSD
- The Veterans Guide to Psychedelic Healing
- Colorado on Ketamine: First Responders Waiver Programs
- Goodbye Alcohol, Hello Ketamine
- Ketamine for COVID?
- Delic Radio: Ketamine Therapy with Dr David Feifel
- New Perspectives on a K-Hole
- Psychedelics Optimize the Brain at Rest
- Recap of Meet Delic Presents: Peace, Love & Ketamine
- Inhabiting John Lily
- My Ketamine Journeys, or Ketamine and the Enchantment of Other Worlds
Ketamine was first investigated as a treatment for depression at Yale University in 2000 — a landmark study that showed a rapid antidepressant effect that persisted for at least three days. Since that first clinical trial, dozens of clinical trials and case reports have followed in support of its antidepressant efficacy. More recently, accumulating evidence suggests ketamine is a promising treatment approach for several other mental health conditions, including bipolar depression, anxiety, PTSD, OCD, and substance use disorders. Below is a curated list of clinical trials, studies and systematic reviews on ketamine’s uses in psychiatry and its mechanisms of action in the brain.
Treatment-resistant Depression (TRD)
- Antidepressant effects of ketamine in depressed patients (2000)
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression (2006)
- Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial (2013)
- Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression (2013)
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression (2016)
- Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD) (2018)
- Ketamine safety and tolerability in clinical trials for treatment-resistant depression (2015)
- Ketamine: A Paradigm Shift for Depression Research and Treatment (2019)
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial (2019)
- Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study (2020)
- Ketamine for Older Adults Pilot (Actively recruiting)
- Low-dose S-ketamine in Women With Prenatal Depression (Actively recruiting)
- A Randomized Add-on Trial of an N-methyl-d-aspartate Antagonist in Treatment-Resistant Bipolar Depression (2010)
- Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials (2020)
- Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis
- A Systematic Review on the Efficacy of Intravenous Racemic Ketamine for Bipolar Depression (2021)
- Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression (2014)
- Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial (2018)
- Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials (2020)
- Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study (2021)
- Intranasal Ketamine for Suicidal Ideation in Veterans (Actively Recruiting)
- Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2017)
- Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disorders (2018)
- Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature (2020)
Post-Traumatic Stress Disorder (PTSD)
- Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial (2014)
- Ketamine as treatment for post-traumatic stress disorder: a review (2019)
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder (2021)
Obsessive-Compulsive Disorder (OCD)
- Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder (2012)
- Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept (2013)
- Ketamine induces immediate and delayed alterations of OCD-like behavior (2020)
Substance Use Disorder Studies
- Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review
- Neural Mechanisms Underlying the Rewarding and Therapeutic Effects of Ketamine as a Treatment for Alcohol Use Disorder (2020)
- Ketamine for the Treatment of Opioid Use Disorder and Depression (Actively Recruiting)
Ketamine Psychedelic Therapy
- Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up (2002)
- Ketamine-Enhanced Psychotherapy: Preliminary Clinical Observations on its Effects in Treating Death Anxiety (2007)
- Ketamine Enhanced Psychotherapy: Preliminary Clinical Observations on Its Effectiveness in Treating Alcoholism (2009)
- Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research (2011)
Mechanism of Action
- NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses (2011)
- Ketamine – More mechanisms of action than just NMDA blockade (2014)
- Mechanisms of ketamine action as an antidepressant (2018)
- Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin (2020)
- Mechanism of Action Underlying Ketamine’s Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression (Actively Recruiting)
The following list of books cover ketamine science and history, its clinical and therapeutic uses, ketamine treatment information, as well as personal accounts and interpretations of the ketamine experience.
- Ketamine: Dreams and Realities by Karl Jansen
- The Scientist: A Metaphysical Autobiography by John C. Lilly
- Journeys into the bright world by Marcia Moore & Howard Alltounian
- Ketamine for Depression by Dr. Stephen J. Hyde
- The Ketamine Papers: Science, Therapy, and Transformation by Phil Wolfson, M.D.
- Ketamine Infusions: A Patients Guide 2nd Edition: Everything You Need To Know Before Going For Ketamine Infusions by Berkeley Jones
- Ketamine for Treatment-Resistant Depression: The First Decade of Progress by Sanjay J. Mathew & Carlos A. Zarate Jr.
- The Little Book of Ketamine by Kit Kelly
- Ketamine: Use and Abuse edited by David T. Yew
Documentaries and Videos
- “Ketamine: Realms and Realities” – Season 2 Episode 5 of the docuseries Hamilton’s Pharmacopeia. In this episode, Hamilton Morris travels to India to uncover the synthesis of industrial ketamine, and explores the role of dissociative anesthetics in society.
- “Eternal K-Hole of the Spotless Mind” – Season 1 Episode 12 from VICE’s High Society. This episode follows the experience of a young man who volunteers to do a ketamine infusion in research investigating whether the drug can weaken rewarding memories associated with alcohol cravings.
- “Ketamine Explained, The Next Big Antidepressant” – An episode from Vice’s The War on Drugs exploring the evolution of ketamine from a club drug to a paradigm-shifting treatment for chronic depression.
- The Experimental Ketamine Cure for Depression – This VICE documentary follows the experience of a ketamine infusion patient named Steven, who finds relief from his chronic depression from repeated treatments.
- Ketamine in Psychiatry: How It Affects Depression, Anxiety, and More – A video by The Drug Classroom overviewing the science and efficacy of ketamine in psychiatry following its discovery as an effective antidepressant in a 2000 clinical trial.
- Ketamine – From Street Drug to Life Saver – A short video featuring Dr. Raquel Bennett, psychologist and founder of the KRIYA Institute, discussing the anti-suicidal and antidepressant properties of ketamine.
- Ketamine Therapy: A Disruptive Treatment Paradigm – A lecture by Andrea and Brent Turnipseed at the 2019 Psychedelic Science Summit hosted by MAPS. The talk overviews the ketamine treatment paradigm and ketamine-assisted psychotherapy.
- Ketamine for Depression and Spiritual Exploration – A talk by Dr. Raquel Bennett at the Psychedelic Science Summit outlining three different treatment protocols for IV ketamine.
- On the Therapeutic Applications of Ketamine with Raquel Bennett and Gisele Fernandes-Osterhold – This online conversation hosted by the California Institute of Integral Studies (CIIS) took place in March 2021 between Dr. Raquel Bennett and CIIS professor Gisele Fernandes-Osterhold. They explore the rapidly growing field of therapeutic ketamine.
- Could a drug prevent depression and PTSD? – A 2016 TED talk by Rebecca Brachman describing the origins of early traditional antidepressants and her surprising preclinical research on Calypsol (ketamine hydrochloride) for stress-induced depression.
Clinics and Integration Therapists
With the psychiatric establishment embracing ketamine as a powerful tool to fight severe mood disorders and chronic pain over recent years, a variety of legal ketamine clinics have sprung up around the country. These clinics are the first legal psychedelic therapy, offering intravenous infusions of off-label racemic ketamine with a treatment plan personalized to each patient.
A comprehensive list of ketamine providers in the United States and internationally can be found on the KRIYA Institute website here. In addition, anyone can explore treatment options on the Ketamine Clinics Directory website, which offers an updated map of US-based ketamine treatment centers and top-rated clinics by state.
Choosing a ketamine clinic can be difficult, with many factors to consider beyond pricing alone. This includes the facility location, the treatment setting, the provider credentials and support staff, the protocols used and more. Be sure to consult past client testimonials on Yelp, Google and Facebook to ensure the clinic is reputable and to evaluate possible strengths and weaknesses before moving forward with treatment.
When it comes to pricing, ketamine infusions typically carry a price tag of $400-800 dollars. Being off-label, and therefore not FDA approved, ketamine infusions are commonly denied coverage by insurance. Be sure to talk with your insurance and prospective provider about the extent of coverage before moving forward with the treatment.
Ketamine-assisted psychotherapy (KAP) is a legal healing approach that utilizes ketamine as an adjunct to enhance the psychotherapeutic process. Ketamine can soften the ego defenses (otherwise known as ego death), allowing difficult material to be processed for deeper healing. This is a good option for those who gained little to no benefit from conventional approaches. Integration follow-up sessions are provided by the clinician following the ketamine-assisted sessions.
For more information on KAP and recommended clinicians in California, consult these links:
- Sage Institute – Berkeley, CA
- Sage Integrative Health – Berkeley, CA
- Polaris Insight Center – San Francisco, CA
- Healing Realms – San Francisco, CA
- The Center for Transformational Psychotherapy – San Francisco, CA
For integration support outside of a KAP context, consult these resources:
- MAPS Psychedelic Integration List – A comprehensive list of international and US-based psychedelic integration therapists.
- Psychedelic Support Network – A list curated by Psychedelic Support of credentialed integration therapists offering services, such as pre-and post-ritual counseling and individual and group psychedelic integration.
CONTRIBUTING RS AUTHOR: DYLAN BEARD
Dylan is a freelance science writer and editor based in the beautiful Pacific Northwest. After finishing his physics degree and dabbling in neuroscience research at UC Santa Barbara in 2017, he returned to his first love—writing. As a long-term fan of the human brain, he loves exploring the latest research on psychedelics, nootropics, psychology, consciousness, meditation, and more. When he’s not writing, you can probably find him on hiking trails around Oregon and Washington or listening to podcasts. Feel free to follow him on Insta @dylancb88.
Disclaimer: Ketamine is potentially categorized as an illegal drug. Reality Sandwich is not encouraging the use of these drugs where prohibited. However, we believe that providing information is imperative for the safety of those who choose to explore these substances. This guide is intended to give educational content and should in no way be viewed as medical recommendations.