Ketamine-Assisted Psychotherapy: An Emerging Treatment for Trauma and Depression

SPECIAL REPORT: PSYCHOTHERAPY

Ketamine-assisted psychotherapy (KAP) is a form of psychotherapy in which the psychedelic properties of ketamine provide an opportunity to explore a patient’s inner psychology with a therapeutic purpose.¹ As a psychedelic, ketamine can induce feelings of calmness, euphoria, and peacefulness, while distorting the perception of space and time. In therapy settings, ketamine can expand insight into the world and one’s personal psychology, leading to the disintegration of self—a psychological process in which a person’s thoughts, emotions, and identity temporarily fall apart, paving the way for a more positive and psychologically healthy reintegration. With moderate ketamine doses, users can find themselves experiencing oneiric images that can be subject to interpretation and analysis by the therapist toward integration of the ketamine experience.^2-4

In the psychiatry realm, ketamine is widely regarded as an effective antidepressant treatment. In these types of clinics, a more traditional model is typically followed in which patients receive ketamine as a pharmacological agent without psychological support. In contrast, KAP gives the protagonism to the psychotherapy component, and offers patients the opportunity to explore feelings, past traumas, or psychological ideas that emerge within the ketamine experience.^5,6

How Is KAP Delivered?

In a typical KAP model, patients go through a medical and a psychiatric evaluation, followed by 1 or 2 preparatory sessions aimed at educating them on what to expect during a ketamine session. These sessions involve education on ketamine’s benefits, risks, and psychedelic effects. Similarly to the philosophy of psychedelic-assisted psychotherapy (PAP), the patient becomes familiar with traditional concepts of psychedelic psychotherapy, such as “set and setting,” integration, and preparation for potential challenging moments. KAP sessions include 1 or 2 therapists and a medical provider who ensure safety, monitoring of the patient’s vitals, facilitation of the session, and psychological integration.¹

During the first ketamine session, therapists welcome the patient and invite them to be open to the experience. Relaxation and breathing exercises help diminish anxiety about the upcoming experience. After the ketamine experience, the patient is encouraged to talk and discuss their insights with the therapist. Drawing or journaling can be used to aid the patient toward that goal.⁷

Can KAP Be Delivered in a Group Setting?

Other modalities of delivering KAP have emerged to improve access to care, integrate, and capitalize on effective elements of other psychotherapeutic modalities. Group KAP is one such approach. Ketamine sessions are conducted in groups of 4 to 12 participants in a safe, controlled environment, where therapists guide clients through their emotional and cognitive experiences. Group settings can enhance therapeutic outcomes by providing a space where psychological and emotional shifts are explored and integrated within a supportive group context, providing a sense of community and shared healing, fostering connection, and reducing feelings of isolation. Participants can process their experiences collectively, benefiting from peer support.^7,8

How Safe Is KAP?

It is important to consider the potential adverse effects and general safety profile of ketamine across these various treatment settings, protocols, and routes of administration. The most frequently reported adverse effects during treatment—such as dissociation, nausea, headache, anxiety/panic, and elevations in heart rate/blood pressure—are typically mild, transient, and resolve without intervention. That said, intravenous administration allows for more flexibility compared with other delivery methods for active titration or rapid discontinuation in real-time. With chronic ketamine exposure, particularly with high doses and frequent use, there is a nontrivial risk of addiction that is thought to be related to the opioid action of ketamine. In these observational settings, there have also been case reports of visceral organ inflammation; however, these appear to be rare even with heavy use, and they have not been observed in clinical settings when treatment follows established dosing guidelines.

There is ongoing research studying the effects of ketamine on cognitive issues and the risk of transition to mania/psychosis in vulnerable individuals. At this time, the evidence does not support the use of ketamine in primary psychotic disorders, pregnancy, or individuals with aneurysmal/hemorrhagic disease, and caution should be used in those with uncontrolled hypertension or elevated intracranial or intraocular pressures. While more research is needed to fully characterize the safety profile, current data support a relatively benign adverse effect profile with good tolerability when administered responsibly and in accordance with clinical standards to individuals without known contraindications.⁹

How Accessible Is KAP?

Research has consistently shown that people of color experience higher rates of mental health disorders while facing significant barriers to accessing care. These challenges often stem from systemic issues such as institutional discrimination, interpersonal racism, and stigma surrounding mental health and seeking treatment. PAP and KAP hold great potential for treating various mental illnesses, including depression, posttraumatic stress disorder (PTSD), substance use disorders (SUDs), racial trauma, and intergenerational trauma—conditions disproportionately affecting communities of color.^10,11 Despite their promise, people of color are underrepresented in the development of PAP and KAP, even though the use of psychedelics originated from indigenous practices across Mesoamerica, South America, and Africa.

Global studies on psychedelics have overwhelmingly focused on non-Hispanic White populations (82.3%), with significantly lower representation among African Americans (2.5%), Latinx individuals (2.1%), Asians (1.8%), and Indigenous people (4.6%).¹² This disparity leaves crucial gaps in understanding the safety, acceptability, efficacy, and effectiveness of PAP and KAP in these populations. The lack of diversity in research participation likely stems from factors such as the predominance of White researchers working in institutions with limited access to diverse populations. Additionally, historical injustices such as the Untreated Syphilis Study at Tuskegee have fostered understandable distrust of medical research among communities of color. The disproportional criminalization of drug-related offenses among the Black community has further deterred minorities from engaging with treatments involving psychedelics and ketamine.

From a clinical standpoint, access to PAP and KAP remains a significant challenge for people of color due to high costs and a lack of insurance coverage. Cultural stigma surrounding mental health and psychedelics also plays a crucial role. For example, many Black individuals view drug use cautiously, prioritizing safety and legal avoidance over exploratory practices. Psychedelics are often perceived as neither safe nor beneficial. Similarly, many Chinese individuals harbor a historical aversion to substances due to the traumatic legacy of the Opium Wars, which resulted in China being forced to cede Hong Kong to Britain, recognize the opium trade as legal, open itself to foreign trade, and grant privileges to foreign powers. Strict drug laws across many Asian countries contribute to Asians’ conservative view of psychedelics, often equating them with abuse.

Therapists providing KAP may also face challenges in serving people of color effectively. In the US, the limited number of therapists from racial and ethnic minorities means that most patients will work with White therapists. Without an understanding of racial trauma, these therapists may unintentionally perpetuate harm through implicit bias. Williams et al documented the experiences of Black female therapists trained by White counterparts and revealed feelings of being misunderstood, frustrated, and apprehensive about discussing cultural aspects during training.¹⁰ To serve diverse populations, therapists must demonstrate cultural competence (Table).^10,13

Future Research Directions

To date, there are no large-scale clinical trials of KAP and the literature seems to agree that this is a next step.^14,15 As such, large-scale, rigorous clinical trials are needed. There have been no trials to date to explore whether ketamine treatment alone, as usually practiced in hospital/medical settings as an antidepressant for treatment-resistant depression (TRD), would benefit significantly by the addition of KAP components. In addition, KAP is currently not covered by insurance, so its private pay nature has kept it outside of academic medical settings. Insurance will not cover KAP unless there is evidence to support its usage cost-wise. Some areas of potential also include the integration of KAP components into the hospital-based ketamine treatment centers.

There is also the potential to integrate psychotherapy with IV ketamine and esketamine practices in medical settings that do not have the staff, insurance reimbursement, or resources to offer such an integrated model. There are no studies demonstrating that elements of KAP integrated into a more traditional medical model would be effective.

Due to the expense of KAP on an individual level, group-based formats could also have benefits, such as healing created in a safe group space where there is learning and witnessing.⁸

A review of KAP for patients with end-of-life medical conditions demonstrated a signal for rapid and transient improvements in psychiatric symptoms and a reduction in psychiatric distress.⁵ This same literature review calls for future research on KAP and existential distress in end-of-life patients.

There may be broader applications to KAP beyond PTSD, SUD, and TRD. It has been suggested that anxiety disorders and existential distress could also be the focus of future research.^5,15 In a more naturalistic study, Dore et al showed that in an outpatient setting, KAP was able to reduce symptoms of anxiety and depression, and larger, more controlled studies would be useful to explore KAP.¹⁶

Concluding Thoughts

KAP can be effective for the management of depression and PTSD. As compared with ketamine alone, KAP can help patients navigate a traumatic experience presented by a psychedelic substance, adding an additional layer of safety. Moreover, we believe the set and setting model and the addition of preparation and integration can positively affect the patient’s experience and impact the outcome. Future research should focus on more representative and inclusive studies further exploring the role of KAP in mental health.

Dr Forcen is the medical director for McLean’s Depression Residential Treatment Program located at the Lincoln Residence, focusing on innovative depression treatments. He is also an assistant professor of psychiatry at Harvard Medical School, and the creator of the psycho-podcast “El último humanista” of The Journal of Humanistic Psychiatry. Dr Zambrano is a clinical fellow in psychiatry at Massachusetts General Hospital and Harvard Medical School. Dr Taylor is an instructor in psychiatry at Harvard Medical School, a staff psychiatrist at McLean Hospital, and a clinical researcher at Massachusetts General Hospital. Dr Nyer is a clinical psychologist at the Depression Clinical and Research Program at Massachusetts General Hospital and an assistant professor of psychology in the Department of Psychiatry at Harvard Medical School. Dr Yeung is the director of Primary Care Research at the Depression Clinical and Research Program at Massachusetts General Hospital and an associate professor of psychiatry at Harvard Medical School.

References

1. Wolfson P, Hartelius G, eds. The Ketamine Papers: Science, Therapy, and Transformation. Multidisciplinary Association for Psychedelic Studies; 2016.

2. Zambrano J, Forcen FE. Challenges with short-term use of intravenous racemic ketamine with psychotherapy for a hospitalized patient with severe posttraumatic stress disorder and depression. J Clin Psychopharmacol. 2023;43(5):462-464.

3. Espi Forcén F. Becoming a ketamine assisted psychotherapist. Psychiatric Times. April 19, 2023. https://www.psychiatrictimes.com/view/becoming-a-ketamine-assisted-psychotherapist

4. Forcén FE, Marengo L, Behn M. Ketamine-assisted meaning-centered psychotherapy for a patient with severe suicidal behavior. Palliat Support Care. 2023;21(2):362-364.

5. Sholevar R, Kromka W, Beaussant Y. Ketamine and ketamine-assisted psychotherapy for psychiatric and existential distress in patients with serious medical illness: a narrative review. J Palliat Med. Published online January 22, 2025.

6. Forcen FE, Nyer M. Ketamine with psychotherapy for the treatment of depression. Psychiatr Ann. 2022;52(9):371-374.

7. Yeung A, Sapirstein G, Crain LD, et al. Pharmacotherapy and ketamine assisted psychotherapy for treatment-resistant depression: a patient with lifelong self-doubt and self-criticism. J Clin Psychiatry. 2023;84(3):23ct14798.

8. Tsang VW, Lin MC, Choles CM, Kryskow P. The effect of ketamine-assisted group therapy on treatment-resistant mental health conditions in firefighters: a prospective observational case series. J Occup Environ Med. Published online February 17, 2025.

9. Wan LB, Levitch CF, Perez AM, et al. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015;76(3):247-252.

10. Williams MT, Reed S, George J. Culture and psychedelic psychotherapy: ethnic and racial themes from three Black women therapists. J Psychedelic Stud. 2020;4(3):125-138.

11. Halstead M, Reed S, Krause R, Williams MT. Ketamine-assisted psychotherapy for PTSD related to racial discrimination. Clin Case Stud. 2021;20(4):310-330.

12. Michaels TI, Purdon J, Collins A, Williams MT. Inclusion of people of color in psychedelic-assisted psychotherapy: a review of the literature. BMC Psychiatry. 2018;18(1):245.

13. Williams MT, Davis AK, Xin Y, et al. People of color in North America report improvements in racial trauma and mental health symptoms following psychedelic experiences. Drugs (Abingdon Engl). 2021;28(3):215-226.

14. Joneborg I, Lee Y, Di Vincenzo JD, et al. Active mechanisms of ketamine-assisted psychotherapy: a systematic review. J Affect Disord. 2022;315:105-112.

15. Mathai DS, Mora V, Garcia-Romeu A. Toward synergies of ketamine and psychotherapy. Front Psychol. 2022;13:868103.

16. Dore J, Turnipseed B, Dwyer S, et al. Ketamine assisted psychotherapy (KAP): patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. J Psychoactive Drugs. 2019;51(2):189-198.