top of page

Breaking Free from Negative Thinking: The Promise of Ketamine Assisted Psychotherapy

It’s no secret that we are in a mental health crisis that was exacerbated by the COVID pandemic, growing economic instability and social unrest. At our clinic we have seen an increase over the last few years in not only the demand for mental heath services, but also an increase in the severity of symptoms. The last few years have taken a toll and it is showing.

Mental health disorders such as depression, anxiety, and complex trauma are a major public health concern worldwide, affecting millions of people. While traditional treatments such as therapy and medication can be effective, many individuals do not respond to these options or experience only partial relief from their symptoms. Ketamine assisted psychotherapy (KAP) has emerged as a promising new treatment option for individuals struggling with mental health disorders, particularly those with treatment-resistant conditions.

As a psychotherapist, I love to explore new approaches that can be more effective for my clients. As a former scientist, I get excited about the neuroscience and love when I can see the science play out in real time in the therapy room.

Let’s start with a little background information about this Miracle Molecule…

The Science Behind Ketamine

Ketamine is a dissociative anesthetic that was developed in the 1960s and is commonly used in Emergency Rooms as a safe sedation approach. Unlike other anesthetics ketamine protects the patient’s airways, which is one of the reasons it is considered to be so safe. But the real reason ketamine is so special in that it works on many different biological pathways and therefore is useful for many different applications. Over the last 2 decades there has been quite a bit of research on uses of ketamine for treating mental health disorders, which is the focus of this article.

Ketamine works, in part, by blocking a receptor in the brain called NMDA, which is involved in the brain's stress and inflammation response and is thought to play a key role in mental health disorders such as treatment resistant depression (TRD) and anxiety disorders including PTSD. In addition, ketamine has also been shown to boost brain function and encourage neuroplasticity - growth of new neuronal connections that allow for new ways of thinking. It does this through increasing the production of brain-derived neurotrophic factor (BDNF). BDNF is a protein that is essential for the growth and survival of neurons, and is known to be decreased in people with mental health disorders. Studies have found that ketamine can improve cognition and memory and there may be a role for ketamine in Long COVID and TBI treatment, though the studies are incomplete and the current evidence is mostly anecdotal.

We have known for some time that ketamine is a powerful and fast acting anti-depressant. Early adopters of ketamine for meant health used it in emergency rooms for acutely suicidal patients and it demonstrated a miraculous response, but sadly very short lived so patients had to keep coming back for more infusions. The search was on for ways to extend the anti-depressant response.

Enter Ketamine Assisted Psychotherapy

Since ketamine alone is an effective anti-depressant, and ketamine also facilitates neuroplasticity, it was theorized that ketamine plus psychotherapy could use this enhanced neuroplasticity to change old thinking pattens and establish and reinforce new ones.

Our brains create neural pathways in response to our experiences and behaviors. Over time, these pathways can become deeply entrenched and difficult to change. You may have heard terms like "core beliefs", "limiting beliefs" or automatic negative thoughts". Ketamine induced neuroplasticity may be the key to helping individuals break free from those old, negative thinking patterns and create new, healthier ways of thinking and behaving.

Ketamine induced neuroplasticity can be compared to a ski slope with fresh snow. The first time someone skis down the slope, they create a path in the snow. If they continue to ski down the same path, it becomes deeper and more entrenched. This is like what happens to our brains over the years - old patterns of negative thinking and behavior get laid down and reinforced. Even when we KNOW those patterns are destructive and we WANT to change them, we keep falling back into them, just like falling into a track on the snow that was laid down ages ago. However, after a fresh snowfall, a new path can be created. Ketamine is like the fresh snow and psychotherapy is the guide to help you find new paths that are healthy and in alignment with your overall wellbeing.

Ketamine assisted psychotherapy involves the use of ketamine in combination with psychotherapy. This approach allows patients to explore their thoughts and emotions in a safe and supportive environment (referred to as "set and setting"), while the ketamine promotes neuroplasticity and boosts brain function and the psychotherapist acts as safety net and gentle guide for finding new paths. A "trip" without an intent or integration is just a trip. But a ketamine journey, done intentionally with set and setting in mind and with follow up integration of the experience, can be life transforming.

Research into Ketamine Assisted Psychotherapy is on the rise and it has been demonstrated to be effective to address a range of mental health disorders, including depression, anxiety, post-traumatic stress disorder (PTSD), and complex PTSD.

Ketamine and the Default Mode Network

The default mode network (DMN) is a network of brain regions that is active when we are not engaged in a specific task or focused on the external environment. The DMN is involved in self-referential thinking, such as reflecting on one's own thoughts and emotions, and in individuals with depression the DMN is often overactive and hyperconnected. Hyperconnectivity in the DMN leads to excessive rumination and negative self-talk, and individuals with depression spend more time in the DMN than individuals without depression.

Ketamine rapidly reduces the activity of the DMN, temporarily shifting the brain from a rigid state to a more chaotic or fluid state. This leads to a decrease in negative self-talk and rumination and is thought to be one of the mechanisms by which ketamine improves mental health outcomes.

In ketamine assisted psychotherapy, the disruption of the DMN can be particularly helpful in allowing individuals to break free from negative thinking patterns. Studies show that individuals with depression who receive ketamine show a significant decrease in DMN activity. By disrupting the DMN, ketamine allows individuals to access new ways of thinking and behaving, promoting neuroplasticity and creating new neural pathways.

Does Ketamine Assisted Psychotherapy Actually Work in Practice?

Research has shown that ketamine-assisted psychotherapy can lead to significant improvements in symptoms of mental health disorders. The effects of the treatment can be long-lasting, with some studies showing improvements in symptoms that last for several months and some showing complete remission of the underlying diagnosis.

Here are some specific research papers demonstrating evidence that supports the effectiveness of ketamine assisted psychotherapy:

  • A 2016 study published in the Journal of Affective Disorders found that ketamine assisted psychotherapy was effective in reducing symptoms of depression and anxiety in patients with treatment-resistant depression. [1]

  • A 2019 systematic review and meta-analysis published in the Journal of Affective Disorders found that ketamine assisted psychotherapy led to significant reductions in depressive symptoms, including in patients with treatment-resistant depression. [2]

  • A 2019 study published in JAMA Psychiatry found that ketamine assisted psychotherapy was effective in reducing symptoms of post-traumatic stress disorder (PTSD), including flashbacks, nightmares, and hyperarousal. [3]

  • A 2020 study published in the Journal of Psychopharmacology found that ketamine assisted psychotherapy was effective in reducing symptoms of depression and anxiety in patients with major depressive disorder. [4]

  • A 2021 study published in the Journal of Psychiatric Research found that ketamine assisted psychotherapy was effective in reducing symptoms of depression in patients with bipolar depression. [5]

How Safe is Ketamine Assisted Psychotherapy?

Ketamine is a safe medication when used under the guidance of a medical professional. The medication has been used as an anesthetic for over 50 years and has a well-established safety profile, often making it thew medication of choice for ER doctors. When used in ketamine-assisted psychotherapy, the medication is administered in a safe and supportive environment, with trained medical professionals monitoring the patient's vital signs. The risk of adverse reactions is low, and the treatment has been shown to be well-tolerated by patients.

What Does the Future hold for Ketamine Assisted Psychotherapy?

While ketamine assisted psychotherapy has shown promise in the treatment of mental health disorders, there are some limitations to be aware of. The treatment can be expensive and is not covered by most insurance plans, though most individuals can receive some partial reimbursement of services. Additionally, the long-term effects of repeated ketamine use are not fully understood, although studies to date have not shown any significant negative effects.

Even though early results of ketamine assisted psychotherapy studies are extremely promising, it is a relatively new treatment and further research is needed to fully understand its potential. Ongoing studies are exploring the use of ketamine assisted psychotherapy in the treatment of mental health disorders and are beginning to explore ketamine for end of life anxiety in terminal patients. Researchers are also investigating ways to optimize the treatment, such as by using different dosing strategies or combining ketamine with other medications or therapies.

Ketamine assisted psychotherapy offers a new perspective on old problems and allows individuals to break free from negative thinking patterns. While further research is needed, ketamine assisted psychotherapy offers hope for those who have not responded to traditional treatments or feel "stuck' In their current treatment. The treatment has been shown to be safe and effective when administered under the guidance of a medical professional in a controlled environment. The outcomes of ketamine assisted psychotherapy are promising, with significant reductions in symptoms of mental health disorders observed in multiple studies. The potential for ketamine assisted psychotherapy to improve the lives of individuals struggling with mental health disorders is an exciting and rapidly developing area of research.

For more information please visit Bay Area Mental Health or contact us at


[1] Wilkinson, S. T., Katz, R. B., Toprak, M., Webler, R., Ostroff, R. B., & Sanacora, G. (2016). Acute and longer-term outcomes using ketamine as a clinical treatment at the Yale Psychiatric Hospital. The Journal of Clinical Psychiatry, 77(4), e471-e477.

[2] Singh, J. B., Fedgchin, M., Daly, E. J., De Boer, P., Cooper, K., Lim, P., ... & Drevets, W. C. (2019). A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. The American Journal of Psychiatry, 176(5), 401-409.

[3] Feder, A., Parides, M. K., Murrough, J. W., Perez, A. M., Morgan, J. E., Saxena, S., ... & Charney, D. S. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA psychiatry, 71(6), 681-688.

[4] Girgenti, M. J., Ghosal, S., LoPresto, D., Taylor, J. R., & Duman, R. S. (2020). Ketamine accelerates fear extinction via mTORC1 signaling. Neurobiology of Disease, 136, 104717.

[5] Niciu, M. J., Luckenbaugh, D. A., Ionescu, D. F., Richards, E. M., Vande Voort, J. L., Ballard, E. D., ... & Zarate Jr, C. A. (2021). Ketamine’s antidepressant efficacy extends to bipolar depression. Journal of Psychiatric Research, 137, 243-250.

354 views0 comments


  • LinkedIn
  • Facebook
  • Instagram
  • google_my_business_icon_137533
bottom of page