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Ketamine for addiction

Studies whose primary subject is both Ketamine and Addiction, 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, Addiction, substance use disorder, then ranked by relevance.

The research suggests ketamine may help reduce craving and support short-term abstinence in some substance use disorders, particularly alcohol and cocaine, especially when combined with psychotherapy. However, the evidence is mixed: meta-analytic benefits appear strongest in the short term (under one month) and weaken or disappear at one to six months, and several trials show inconsistent relapse-prevention effects. A major caveat is that ketamine itself carries a well-documented risk of misuse and dependence, and much of the positive evidence comes from small pilot trials.

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 use: a review 2011 systematic review Opposes Chronic frequent ketamine use is associated with ulcerative cystitis, neurocognitive impairment (especially working and episodic memory deficits), and addiction concerns, with many users reporting failed attempts to stop.
Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research 1997 controlled clinical trial 211 Supports Ketamine psychedelic therapy added to standard alcoholism treatment produced a 65.8% one-year abstinence rate versus 24% with conventional treatment alone.
Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. 2002 RCT 70 Supports High-dose ketamine psychotherapy (2.0 mg/kg) produced significantly greater abstinence, reduced craving, and improved emotional attitudes over two years compared with low-dose ketamine psychotherapy.
Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review 2021 systematic review Mixed Systematic reviews and meta-analyses support robust, rapid, transient antidepressant and anti-suicidal effects of ketamine, but evidence for other indications including substance use disorders is less established.
A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial. 2019 RCT 40 Supports A single ketamine infusion significantly increased likelihood of abstinence, delayed time to relapse, and reduced heavy drinking days compared with midazolam.
A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. 2019 RCT 55 Supports A single ketamine infusion significantly increased abstinence (48.2% vs 10.7%), reduced relapse risk by 53%, and lowered craving by 58.1% compared with midazolam.
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 2007 RCT 59 Supports Three sessions of ketamine-assisted psychotherapy led to a significantly higher one-year abstinence rate (50%) than a single session (22.2%), with no differences in depression, anxiety, or craving.
Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder 2022 RCT 96 Mixed Ketamine infusions led to significantly more days abstinent at six months compared with placebo, but relapse rates did not differ significantly between groups.
Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder 2019 RCT Supports Naltrexone pretreatment did not diminish the antidepressant effects of ketamine.
Brain damages in ketamine addicts as revealed by magnetic resonance imaging 2014 observational cohort 21 Opposes Chronic ketamine abuse was associated with cortical atrophy and lesions in frontal, parietal, and occipital cortices appearing 2-4 years after addiction.
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder 2018 narrative review Supports High body mass index and a positive family history of alcohol use disorder were the most replicated pretreatment predictors of response to ketamine in treatment-resistant depression.
Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature 2021 systematic review Unclear Ketamine and esketamine show promise for treating substance use disorders, but solid evidence for benefits in addiction is still lacking.
Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial. 2021 RCT 40 Supports Mystical-type effects of ketamine, but not dissociation, mediated the reduction in at-risk drinking behavior in alcohol-dependent adults.
A sub-set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study. 2018 RCT Supports Mystical-type effects, but not dissociation or near-death experiences, mediated the effect of ketamine on reducing cocaine use and craving.
Family history of alcohol dependence and antidepressant response to an N‐methyl‐D‐aspartate antagonist in bipolar depression 2012 post hoc analysis of pooled RCT data 33 Supports A positive family history of alcohol dependence predicted a greater and more sustained antidepressant response to ketamine in individuals with bipolar depression.
Novel pharmacotherapies for opioid use disorder and opioid withdrawal 2026 narrative review Mixed Ketamine has preliminary randomized evidence suggesting potential effects on abstinence, withdrawal, craving, and psychotherapy augmentation in opioid use disorder, but controlled evidence is limited.
Ketamine for substance use disorders: a systematic review and meta-analysis 2026 systematic review and meta-analysis 798 Mixed Ketamine significantly improved short-term abstinence (under one month, OR=3.27) but not longer-term abstinence (one to six months, OR=1.74, not significant), with no significant difference in dropout or adverse events.
S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats 2026 experimental animal study Mixed S-ketamine, but not R-ketamine, dose-dependently suppressed binge-like alcohol self-administration in male rats, but tolerance developed rapidly with repeated administration.
Treating addiction with an addictive drug: the ketamine paradox revisited 2026 narrative review Mixed Ketamine combined with psychotherapy shows promising reductions in craving and increases in abstinent days for alcohol and cocaine use disorders in small-to-moderate Phase 2 trials, but effects on relapse prevention are inconsistent and the drug carries a well-established risk of misuse.
Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance. 2026 retrospective cohort study 30670 Opposes Esketamine users with comorbid substance use disorder had higher risks of self-harm, suicide attempt, emergency visits, hospitalization, and mortality compared with esketamine users without substance use disorder.
Associations between substance use treatment and ketamine use: A hypothesis-generating analysis. 2026 cross-sectional survey analysis 173808 Opposes Past-year substance use disorder treatment was associated with higher odds of past-year ketamine use across multiple substance domains, including alcohol, opioid, and methamphetamine use disorders.
Targeting craving with ketamine treatment in substance use disorders : a systematic review and meta-analysis 2026 systematic review and meta-analysis 389 Supports Ketamine was associated with a significant reduction in craving compared with control across substance use disorders, and with increased likelihood of abstinence.
Ketamine Dependence: Clinical Characteristics of an Inpatient Detoxification Population With Complex Physical Health Needs 2026 retrospective cross-sectional study 59 Opposes Ketamine detoxification admissions increased over time, with patients showing prolonged high-dose use (mean 5.4 g/day, 5.2 years), urological pathology, and hepatic injury; most completed detoxification.
Ketamine addiction following a single sub-anaesthetic ketamine treatment for acute suicidality in a psychiatrically multimorbid patient: case report 2026 case report 1 Opposes A single sub-anaesthetic dose of intranasal ketamine was followed by the development of ketamine addiction, with subsequent polysubstance abuse and significant psychosocial impairment.
Ketamine Use in Self-Described Therapeutic Contexts: A Thematic Analysis of Reddit Posts 2026 qualitative content analysis 500 Mixed Ketamine use outside clinical settings was characterized by high doses, frequent psychological adverse effects, and concurrent polydrug use, highlighting the need for clinical monitoring.

Points of agreement

  • Ketamine combined with psychotherapy shows promise for reducing craving and increasing short-term abstinence in alcohol and cocaine use disorders.
  • The strongest and most consistent benefits appear in the short term (under one month), with effects weakening or becoming inconsistent at longer follow-up.
  • Ketamine carries a well-documented risk of misuse, dependence, and physical harms (e.g., bladder and cognitive effects) that must be weighed against therapeutic benefits.
  • Mystical-type psychoactive effects may mediate ketamine's impact on substance use behavior.

Conflicts

  • Some trials report significant reductions in relapse or increased abstinence at longer follow-up, while meta-analytic pooling finds no significant benefit beyond one month.
  • Some studies report robust abstinence benefits for heroin and alcohol, while others find no significant difference in relapse rates.
  • Evidence on safety is mixed: some trials report no significant adverse event differences, while others document serious harms including addiction, cortical atrophy, and elevated risks in comorbid populations.

Gaps

  • Durability of abstinence effects beyond six months is not well established.
  • Optimal dosing, number of sessions, and route of administration remain unclear.
  • Blinding integrity and comparator conditions vary widely across trials.
  • Long-term safety data, including abuse liability in clinical populations, are limited.
  • Effects in populations with comorbid psychiatric and substance use disorders are understudied.
  • Most positive trials are small pilot studies, limiting generalizability.
Browse these studies in the library

Common questions

What does the research agree on about ketamine for addiction?
  • Ketamine combined with psychotherapy shows promise for reducing craving and increasing short-term abstinence in alcohol and cocaine use disorders.
  • The strongest and most consistent benefits appear in the short term (under one month), with effects weakening or becoming inconsistent at longer follow-up.
  • Ketamine carries a well-documented risk of misuse, dependence, and physical harms (e.g., bladder and cognitive effects) that must be weighed against therapeutic benefits.
  • Mystical-type psychoactive effects may mediate ketamine's impact on substance use behavior.
Where do studies on ketamine for addiction conflict?
  • Some trials report significant reductions in relapse or increased abstinence at longer follow-up, while meta-analytic pooling finds no significant benefit beyond one month.
  • Some studies report robust abstinence benefits for heroin and alcohol, while others find no significant difference in relapse rates.
  • Evidence on safety is mixed: some trials report no significant adverse event differences, while others document serious harms including addiction, cortical atrophy, and elevated risks in comorbid populations.
What is still unknown about ketamine for addiction?
  • Durability of abstinence effects beyond six months is not well established.
  • Optimal dosing, number of sessions, and route of administration remain unclear.
  • Blinding integrity and comparator conditions vary widely across trials.
  • Long-term safety data, including abuse liability in clinical populations, are limited.
  • Effects in populations with comorbid psychiatric and substance use disorders are understudied.
  • Most positive trials are small pilot studies, limiting generalizability.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Ketamine for addiction, 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 for addiction 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

127 articles · 62 from the last two years · 354,299 participants across 50 studies reporting sample size

Common study designs

review 27 narrative review 7 systematic review 11 experimental study 9 randomized controlled trial 16

Research volume by year

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124 studies whose primary subject is ketamine for addiction since 2002

Studies about ketamine for addiction per year, 2002 to 2026, peaking at 35 in 2025 Bar chart: one bar per year, taller where more studies were published that year. 0 20 40 2005 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about ketamine for addiction per year, 2002 to 2026, peaking at 35 in 2025
Year Studies
2002 1
2003 0
2004 0
2005 0
2006 0
2007 1
2008 0
2009 0
2010 0
2011 3
2012 1
2013 0
2014 5
2015 2
2016 0
2017 1
2018 2
2019 6
2020 3
2021 6
2022 12
2023 8
2024 19
2025 35
2026 19

Research

Synthesize the evidence →

Novel pharmacotherapies for opioid use disorder and opioid withdrawal

Frontiers in Psychiatry September 3, 2026 Mary R. Shen, Kwadwo Owusu-Boaitey, Zackari D. Murphy et al.

IntroductionOpioid use disorder (OUD) remains a major public health crisis despite evidence-based medications, including methadone, buprenorphine, and naltrexone. Persistent challenges with treatment retention, access, stigma, and incomplete response highlight the need for adjunctive pharmacotherapies targeting neurobiological systems beyond the mu-opioid receptor.MethodsWe conducted a...

DOI: 10.3389/fpsyt.2026.1909149 (opens in new tab) Full text (opens in new tab) Addiction Ketamine Cannabinoid Drug +2

Ketamine for substance use disorders: a systematic review and meta-analysis

Frontiers in Psychiatry July 17, 2026 Shu-Ping Fang, Xin Yang, Da-Cong Zhao et al.

Introduction Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD. This study aimed to evaluate the efficacy and safety of ketamine in treating SUD. Methods Multiple databases were...

DOI: 10.3389/fpsyt.2026.1835709 (opens in new tab) Ketamine Abstinence Adverse effect Randomized controlled trial +6

S-ketamine, but not R-ketamine, transiently suppresses front-loaded binge-like alcohol self-administration in male rats

July 12, 2026 Fahd François Hilal, Méléna Dreinaza, Quentin Lebel et al.

Background and Purpose: Ketamine has emerged as a promising treatment candidate for alcohol use disorder (AUD), yet whether its S- and R-enantiomers differentially regulate ongoing binge-like alcohol self-administration remains unknown. We compared the acute and repeated effects of S- and R-ketamine in a chronic binge-like, front-loaded operant alcohol self-administration paradigm. Experimental...

DOI: 10.22541/authorea.15005962/v1 (opens in new tab) Ketamine Alcohol use disorder Ethanol Sedative +9

Treating addiction with an addictive drug: the ketamine paradox revisited

Frontiers in Psychiatry July 9, 2026 Alqassem Y. Hakami

Background Substance use disorders (SUDs) and treatment-resistant depression (TRD) remain a major global health challenge, marked by high relapse rates and limited long-term effectiveness of existing treatments. Ketamine, a glutamatergic modulator with rapid neuroplastic effects, has emerged as a novel intervention for TRD and is increasingly investigated as an adjunctive treatment for...

DOI: 10.3389/fpsyt.2026.1866092 (opens in new tab) Addiction Ketamine Neuroplasticity Treatment-resistant depression +14

Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance.

Journal of Affective Disorders June 8, 2026 Dian‐jeng Li, Tien-Wei Hsu, Te-Chang Changchien et al.

Little is known about esketamine's effectiveness for patients with major depressive disorder (MDD) comorbid substance use disorders (SUD). We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults aged ≥18 years with MDD. Three propensity-score-matched (1:1) cohorts were defined based on treatment: esketamine, antidepressant-only, and repetitive...

DOI: 10.1016/j.jad.2026.122106 (opens in new tab) Full text (opens in new tab) Esketamine Major depressive disorder Substance use disorder Mortality +1

Ketamine Dependence: Clinical Characteristics of an Inpatient Detoxification Population With Complex Physical Health Needs

BJPsych Open June 1, 2026 Sarah Shackleton, Onuswale Oni, Stephen J. Kaar

Aims: Recreational ketamine use and treatment-seeking for associated complications is increasing in England. Complications of ketamine dependence can be debilitating, leading to continued dependence and surgical intervention. However, treatment remains under-researched, with lacking understanding of those seeking treatment or requiring specialist inpatient detoxification. This study aims to...

DOI: 10.1192/bjo.2026.11591 (opens in new tab)

Targeting craving with ketamine treatment in substance use disorders : a systematic review and meta-analysis

Open MIND June 1, 2026 Kellie Elkrief

Les troubles liés à l’usage de substances (TUS) touchent environ 2 % de la population mondiale et sont associés à une morbidité importante ainsi qu’à un risque de rechute élevé. Les envies impérieuses (le craving), définies comme une envie intense de consommer une substance, constituent une caractéristique centrale et transdiagnostique des TUS et représentent un prédicteur clé de rechute. Les...

DOI: 10.71781/34775 (opens in new tab) Craving Substance use Population Psychoactive substance +1

Associations between substance use treatment and ketamine use: A hypothesis-generating analysis.

Addictive behaviors reports June 1, 2026 Fares Qeadan, Shanti O'Neil 1 citation

Ketamine is increasingly used in clinical settings for mental health and pain management, yet its misuse poses public health risks. While prior studies have examined ketamine trends, few have explored its use among individuals receiving treatment for substance use disorders (SUD). Using 2021-2023 data from the National Survey on Drug Use and Health (NSDUH), we analyzed the association between...

DOI: 10.1016/j.abrep.2025.100650 (opens in new tab) Full text (opens in new tab) Ketamine Substance use disorder Drug treatment Hallucinogens +2

Ketamine addiction following a single sub-anaesthetic ketamine treatment for acute suicidality in a psychiatrically multimorbid patient: case report

BJPsych Open May 1, 2026 Gijsbrecht H. J. Roelandt, Jurriaan F M Strous, Jeanine Kamphuis et al.

Summary This case report presents the case of a 25-year-old woman who developed ketamine addiction following a single sub-anaesthetic dose of intranasal ketamine in a pilot study investigating intranasal racemic ketamine for acute suicidality. She had a history of depression, obsessive–compulsive disorder, autism spectrum disorder and anorexia nervosa, and she had sporadically used alcohol and...

DOI: 10.1192/bjo.2026.11012 (opens in new tab)

Ketamine Use in Self-Described Therapeutic Contexts: A Thematic Analysis of Reddit Posts

Behavioral Sciences March 24, 2026 J. Richard Kendrick, Ghonwa Ahmad, Audrey Wood et al.

The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders...

DOI: 10.3390/bs16040480 (opens in new tab) Ketamine Addiction Thematic analysis Adverse effect +4

Clinical trials

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