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Ketamine and psychedelic-assisted therapy

Studies whose primary subject is both Ketamine and Psychedelic-assisted therapy, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Ketamine, racemic ketamine, arketamine, R-ketamine, Psychedelic-assisted therapy, psychedelic therapy, then ranked by relevance.

The research on ketamine-assisted psychotherapy (KAP) is generally positive: controlled trials in addiction, observational studies in depression/anxiety/PTSD, and small trials report meaningful symptom reductions and higher abstinence or remission rates, with some evidence that repeated sessions and higher (psychedelic) doses outperform single or low doses. Results are less consistent for durability and for whether psychotherapy adds to ketamine alone: one nonrandomized trial found a remission advantage at treatment end that did not persist at six months, and a meta-analysis found subjective effects explain only a modest share of ketamine's benefit. The main caveats are small samples, open-label or retrospective designs, high attrition, and few randomized trials of KAP itself.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Study Design Sample size Direction Finding
Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research 1997 controlled clinical trial 211 Supports Adding ketamine psychedelic therapy to standard alcoholism treatment produced 65.8% one-year abstinence versus 24% with conventional treatment alone.
Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. 2002 RCT 70 Supports High-dose (2.0 mg/kg) ketamine psychotherapy produced greater two-year abstinence, larger and longer craving reduction, and greater emotional-attitude change than low-dose (0.2 mg/kg) ketamine psychotherapy.
Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy 2019 observational study 235 Supports KAP was reported effective for decreasing depression and anxiety, especially in older patients and those with severe symptom burden.
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 2007 RCT 59 Supports Three KAP sessions yielded 50% one-year abstinence versus 22.2% after a single session, with no group differences in depression, anxiety, or craving.
The need for establishing best practices and gold standards in psychedelic medicine. 2023 review Unclear Argues that the medical community should develop standards of care and gold standards for psychedelic-assisted therapy based on data quality, trial rigor, and comparative safety and efficacy.
A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression 2022 quality improvement evaluation, mixed methods 94 Supports A community-of-practice KAP program was associated with clinically significant improvements in depression, PTSD, anxiety, and work/life functionality.
Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychopathological Psychotic Experiences and Psychotic Disorders 2024 qualitative study 12 Supports Experts agreed that psychedelic-, ketamine-, and MDMA-assisted psychotherapy with high support are not necessarily contraindicated for people with psychotic conditions and may benefit some.
Ketamine-assisted psychotherapy in adolescents with multiple psychiatric diagnoses. 2023 case series 4 Supports Four adolescents with complex treatment-resistant disorders showed symptomatic and functional improvement on KAP and tolerated it well.
Phenomenology and therapeutic potential of patient experiences during oral esketamine treatment for treatment-resistant depression: an interpretative phenomenological study. 2023 qualitative study (IPA) 17 Mixed Esketamine experiences were highly variable and psychological distress was common, though some effects such as openness and detachment were seen as having psychotherapeutic potential.
A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review. 2024 systematic review Supports Both 25 mg psilocybin and 56/84 mg esketamine showed clinically meaningful number-needed-to-treat estimates with acceptable harm profiles in treatment-resistant depression.
Ketamine-assisted psychotherapy, psychedelic methodologies, and the impregnable value of the subjective—a new and evolving approach 2024 theoretical paper Supports Argues that ketamine's dissociative and ego-dissolving effects are intrinsic to its therapeutic action rather than side effects, especially within a supportive therapeutic setting.
Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome. 2024 systematic review and meta-analysis 654 Supports Subjective effects modestly mediated therapeutic outcomes for ketamine (R2 5-10%) and more strongly for psilocybin (R2 24%), with a larger mediating effect in substance use disorder than depression.
Ketamine-Assisted Psychotherapy Provides Lasting and Effective Results in the Treatment of Depression, Anxiety, and Post-Traumatic Stress Disorder at 3 and 6 Months: Findings from a Large Retrospective Effectiveness Study. 2024 retrospective effectiveness study 346 Supports KAP produced large treatment effects on depression, anxiety, and PTSD symptoms at 3 months (d = 0.75-0.86) and 6 months (d = 0.61-0.73), though attrition was very high.
The Efficacy of Psychedelic-Assisted Therapy in Managing Post-traumatic Stress Disorder (PTSD): A New Frontier? 2022 review Unclear Reviews evidence for MDMA, ketamine, classical psychedelics, and cannabis in PTSD and concludes psychedelic-assisted therapy shows potential but more research is needed.
Ketamine and Ketamine-Assisted Psychotherapy for Psychiatric and Existential Distress in Patients with Serious Medical Illness: A Narrative Review. 2025 narrative review Supports Nine studies and 12 case reports reported positive results and good safety for ketamine or KAP, but most involved ketamine as a pharmacologic agent and KAP for existential distress remains largely unstudied.
Longitudinal peripheral DNA methylation remodeling following ketamine-assisted psychotherapy in major depressive disorder 2026 longitudinal observational study 10 Supports Depressive symptoms declined markedly (BDI-II from severe to mild range) after three intranasal ketamine sessions with psychotherapy, alongside exploratory DNA methylation changes the authors say do not establish causality.
Ketamine administered biomedically or as psychedelic-assisted therapy in treatment-resistant depression: Differing efficacy based on depressive subtype or presence of childhood trauma? 2026 commentary Mixed Argues that ketamine's efficacy should be examined by depressive subtype and childhood trauma, reports preliminary open-label findings that biomedical ketamine may be superior in melancholic depression, and notes that studies of ketamine combined with psychotherapy are lacking.
Oral Ketamine-Assisted Psychotherapy Leading to Prolonged Remission in Recurrent Dissociative Neurological Symptom Disorder With Mutism: A Case Report 2026 case study 1 Supports Six oral KAP sessions (50-150 mg) restored spontaneous speech sustained over a year after prior treatments failed; the authors call this hypothesis-generating.
A longitudinal analysis of the clinical practice of ketamine assisted psychotherapy with adolescents and young adults 2026 observational cohort 19 Supports BDI-II declined about 0.65 points per visit and HAM-A about 0.21 points per visit; 63% achieved medium or large depression effects and clinicians and patients reported benefit in 68% of cases.
Making Play Safe Again: Ketamine-Assisted Psychotherapy with Traumatized Autistic Adults 2026 theoretical paper Supports Argues that KAP creates a transitional space in which autistic adults can safely access and integrate trauma material with a therapist.
Oncology Providers' Perspectives on Psychedelic-Assisted Therapy. 2026 cross-sectional survey 385 Opposes 80% of oncology providers did not feel comfortable counseling patients on psychedelic-assisted therapy and only 44% were familiar with its legal status.
Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial. 2026 mixed-methods randomized pilot trial Mixed KAP was feasible and acceptable, both groups had reduced pain intensity and improved mood, and qualitative findings suggested psychotherapy may add psychological benefit; the pilot was small.
Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy 2026 nonrandomized open-label trial 46 Mixed KAP added to subcutaneous esketamine produced lower MADRS scores at sessions seven and eight and higher remission (78.3% vs 34.8%) at completion, but no group differences persisted over six months.
The Hidden Architecture of Psychedelic Therapy How Music Shapes Emotion, Imagery, Memory, Surrender, and Ketamine Tolerability A White Paper Based on 41 Studies of Music in Psychedelic- 2026 review Supports Across 41 studies, music appears as an active session-shaping variable in psychedelic and ketamine therapy, organizing emotion and imagery and making ketamine treatment more tolerable.
Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study 2026 case study 1 Supports Greater therapeutic gains followed KAP sessions with higher mystical-experience scores, and the patient attributed improvement to the psychological and spiritual impact of the experiences.

Points of agreement

  • Controlled and observational studies in addiction, depression, anxiety, and PTSD generally report symptom reduction or higher abstinence with KAP.
  • Higher or repeated psychedelic-dose ketamine sessions outperform single or low non-hallucinogenic doses in addiction trials.
  • Subjective/psychedelic experiences are reported to contribute to therapeutic outcomes, though the measured mediating effect is modest for ketamine.
  • Several sources argue that the therapeutic setting, relationship, and integration are central to KAP.

Conflicts

  • One nonrandomized trial found a remission advantage for KAP over ketamine alone at treatment end, while another analysis found no persisting group difference at six months.
  • A meta-analysis found subjective effects explain only a small share of ketamine's benefit, whereas case reports and theoretical papers emphasize mystical or dissociative experiences as central.
  • Some sources frame ketamine's dissociative effects as therapeutic, while clinical phenomenology reports frequent distress and fear during sessions.

Gaps

  • Few randomized controlled trials isolate the psychotherapy component of KAP from ketamine's pharmacologic effect.
  • Durability beyond six to twelve months is poorly established, and retrospective studies show very high attrition.
  • Blinding is difficult with psychedelic doses, and most KAP evidence is open-label, retrospective, or case-based.
  • Adolescent, palliative, chronic pain, autistic, and psychotic-population evidence is limited to small series, pilots, or expert opinion.
  • Optimal dose, session number, route, and integration protocol are not standardized.
Browse these studies in the library

Common questions

What does the research agree on about ketamine and psychedelic-assisted therapy?
  • Controlled and observational studies in addiction, depression, anxiety, and PTSD generally report symptom reduction or higher abstinence with KAP.
  • Higher or repeated psychedelic-dose ketamine sessions outperform single or low non-hallucinogenic doses in addiction trials.
  • Subjective/psychedelic experiences are reported to contribute to therapeutic outcomes, though the measured mediating effect is modest for ketamine.
  • Several sources argue that the therapeutic setting, relationship, and integration are central to KAP.
Where do studies on ketamine and psychedelic-assisted therapy conflict?
  • One nonrandomized trial found a remission advantage for KAP over ketamine alone at treatment end, while another analysis found no persisting group difference at six months.
  • A meta-analysis found subjective effects explain only a small share of ketamine's benefit, whereas case reports and theoretical papers emphasize mystical or dissociative experiences as central.
  • Some sources frame ketamine's dissociative effects as therapeutic, while clinical phenomenology reports frequent distress and fear during sessions.
What is still unknown about ketamine and psychedelic-assisted therapy?
  • Few randomized controlled trials isolate the psychotherapy component of KAP from ketamine's pharmacologic effect.
  • Durability beyond six to twelve months is poorly established, and retrospective studies show very high attrition.
  • Blinding is difficult with psychedelic doses, and most KAP evidence is open-label, retrospective, or case-based.
  • Adolescent, palliative, chronic pain, autistic, and psychotic-population evidence is limited to small series, pilots, or expert opinion.
  • Optimal dose, session number, route, and integration protocol are not standardized.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Ketamine and psychedelic-assisted therapy, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Ketamine and psychedelic-assisted therapy or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

92 articles · 47 from the last two years · 6,436 participants across 52 studies reporting sample size

Common study designs

review 16 case study 9 case report 5 narrative review 5 systematic review 9

Research volume by year

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88 studies whose primary subject is ketamine and psychedelic-assisted therapy since 2002

Studies about ketamine and psychedelic-assisted therapy per year, 2002 to 2026, peaking at 22 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 15 30 2005 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about ketamine and psychedelic-assisted therapy per year, 2002 to 2026, peaking at 22 in 2025
Year Studies
2002 1
2003 0
2004 0
2005 0
2006 0
2007 1
2008 0
2009 0
2010 0
2011 0
2012 0
2013 0
2014 1
2015 0
2016 0
2017 0
2018 1
2019 2
2020 0
2021 4
2022 6
2023 10
2024 18
2025 22
2026 22

Research

Synthesize the evidence →

Longitudinal peripheral DNA methylation remodeling following ketamine-assisted psychotherapy in major depressive disorder

Epigenetics October 15, 2026 Arghavan Nepton, Sonya C. Faber, Zachary A. Kaminsky et al.

Ketamine produces rapid antidepressant effects, but the molecular processes associated with their persistence remain poorly defined in humans. We examined longitudinal DNA methylation changes in 10 adults with major depressive disorder undergoing ketamine-assisted psychotherapy using two pre-treatment assessments (T1, T2) and one post-treatment assessment (T3). Participants received three...

DOI: 10.1080/15592294.2026.2731659 (opens in new tab)

Ketamine administered biomedically or as psychedelic-assisted therapy in treatment-resistant depression: Differing efficacy based on depressive subtype or presence of childhood trauma?

Australasian Psychiatry October 13, 2026 Adam Bayes, Colleen Loo

ObjectiveThe ideas presented in this paper are based on a presentation at a festschrift event marking the retirement of Professor Gordon Parker from UNSW, Sydney. Drawing on Gordon's depressive subtyping approach and his critiques of a unitary view of major depressive disorder and treatment-resistant depression (TRD), we aim to (i) explore differing models of ketamine for TRD - biomedical...

DOI: 10.1177/10398562261494440 (opens in new tab) Full text (opens in new tab)

Oral Ketamine-Assisted Psychotherapy Leading to Prolonged Remission in Recurrent Dissociative Neurological Symptom Disorder With Mutism: A Case Report

Cureus October 12, 2026 Anirudh Bakam

Dissociative neurological symptom disorder (DNSD), termed functional neurological symptom disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), presents with neurological symptoms not explained by structural disease.The first line treatment of DNSD is psychotherapy, but when the conflict maintaining the symptoms cannot be put into words,...

DOI: 10.7759/cureus.117827 (opens in new tab) Full text (opens in new tab)

A longitudinal analysis of the clinical practice of ketamine assisted psychotherapy with adolescents and young adults

Frontiers in Psychiatry September 21, 2026 Phil Wolfson, Cody Carroll

Introduction Ketamine Assisted Psychotherapy (KAP) is a developing modality with broad impact on humans suffering with a variety of emotional and relationship difficulties that encompass many diagnostic entities. Our application of KAP has extended to and included the treatment of adolescents and young adults in a family therapy format. Given the increasing scope and complexity of the...

DOI: 10.3389/fpsyt.2026.1886833 (opens in new tab)

Making Play Safe Again: Ketamine-Assisted Psychotherapy with Traumatized Autistic Adults

Psychoanalytic Inquiry August 28, 2026 Diana Moga

Autistic individuals are more susceptible to trauma due to higher baseline anxiety and overwhelm; poorer episodic memory; and the frequent lack of a sense of community, safety, and belonging that are both protective and needed to heal from trauma. Furthermore, many autistic adults have adopted a false self to get by in a neurotypical world and are often cut off from their affective, embodied...

DOI: 10.1080/07351690.2026.2721958 (opens in new tab)

Oncology Providers' Perspectives on Psychedelic-Assisted Therapy.

The American journal of hospice & palliative care August 28, 2026 Krishna Hanubal, Akul Munjal, Jino Park et al.

PurposeDespite most psychedelic substances remaining Schedule I, clinical research exploring psychedelic-assisted therapy (PAT) in oncology is expanding. We sought to assess oncology providers' attitudes toward and understanding of PAT.MethodsWe conducted a cross-sectional survey of healthcare professionals involved in oncology across five academic institutions in California, South Carolina,...

DOI: 10.1177/10499091261483604 (opens in new tab) Full text (opens in new tab) MDMA Ketamine Psilocybin Antidepressants +4

Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy

Journal of Affective Disorders August 10, 2026 Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa et al.

BACKGROUND: Ketamine is an effective rapid-acting treatment for treatment-resistant depression (TRD), producing antidepressant effects within hours of administration. Because it induces states of heightened neuroplasticity and psychological openness, psychotherapy may enhance its therapeutic effects. METHODS: This exploratory, nonrandomized, open-label clinical trial evaluated the adjunctive...

DOI: 10.1016/j.jad.2026.122369 (opens in new tab)

The Hidden Architecture of Psychedelic Therapy How Music Shapes Emotion, Imagery, Memory, Surrender, and Ketamine Tolerability A White Paper Based on 41 Studies of Music in Psychedelic-

Zenodo (CERN European Organization for Nuclear Research) July 21, 2026 Michael Alvear preprint

Music is often treated as an atmospheric accessory in psychedelic and ketamine therapy: useful, pleasant, optional, or merely calming. That framing is too weak. Across a curated evidence base of 41 studies, reviews, mechanistic papers, clinical reports, playlist-design papers, ketamine-specific studies, ceremonial-music papers, and counterarguments, music repeatedly appears as an active...

DOI: 10.5281/zenodo.21480416 (opens in new tab)

Mystical Experiences as Catalysts in Ketamine-Assisted Psychotherapy: A Case Study

Journal of Psychoactive Drugs July 3, 2026 Miguel Joaquim Soares Teles Couceiro, Victor José da Conceição Teixeira Amorim Rodrigues, Nuno Manuel Correia Torres

This case study explores the potential role of mystical-type experiences in ketamine-assisted psychotherapy (KAP). A patient with generalized anxiety disorder and migraines underwent four intramuscular KAP sessions (0.5-0.9 mg/kg). Outcomes were assessed using the Outcome Questionnaire-45 (OQ-45), the Hood Mysticism Scale (HMS), and interviews. Greater therapeutic gains followed sessions with...

DOI: 10.1080/02791072.2026.2696253 (opens in new tab) Mysticism Anxiety disorder Therapeutic relationship Outcome game theory +4

Clinical trials

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