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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 24 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.

Ketamine, given as a single or short series of subanesthetic infusions alongside psychological therapy, shows a consistent short-term signal for reducing substance use and craving in alcohol, cocaine, and heroin use disorders, with some trials reporting large abstinence differences versus active controls. However, meta-analytic pooling finds the abstinence advantage is significant only under one month and not at one to six months, and the largest trials show smaller or non-significant relapse differences, so durability is the central caveat. Samples are small, mostly single-site, and ketamine's own misuse liability and harms with chronic use complicate the risk-benefit picture.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. All 25 matching studies were reviewed; the 24 that directly address the question are shown here.

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 Ketamine psychedelic therapy added to standard alcoholism treatment yielded 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 abstinence over two years, longer-lasting craving reduction, and greater emotional-attitude change than low-dose (0.2 mg/kg) ketamine psychotherapy.
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence 2007 RCT 59 Supports Three ketamine-assisted psychotherapy sessions gave higher one-year abstinence (50% vs 22.2%) than a single session, with no group differences in depression, anxiety, or craving.
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 (0.71 mg/kg) increased likelihood of abstinence, delayed relapse, and reduced heavy drinking days versus midazolam over 21 days.
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 (0.5 mg/kg) produced 48.2% end-of-study abstinence versus 10.7% with midazolam, a 53% lower relapse hazard, and 58.1% lower craving.
Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder 2022 RCT 96 Mixed Three ketamine infusions increased days abstinent at six months versus saline (mean difference 10.1%), but relapse rates did not differ significantly.
Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial. 2021 RCT (secondary analysis) 40 Supports Ketamine reduced at-risk drinking, and mystical-type effects but not dissociation mediated the reduction.
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 (laboratory study) Supports Mystical-type effects, but not dissociation or near-death experiences, mediated ketamine's effect on decreased cocaine use and craving.
Mechanisms of anti-depressant and anti- alcohol effects of ketamine in patients with alcohol use disorder 2026 secondary analysis of RCT Mixed Ketamine reduced anhedonia and repetitive negative thoughts at 3 months but not 6 months; among those with a family history of alcohol use disorder, craving reduction mediated increased abstinent days.
No Heavy Drinking Days and Percentage of Days Abstinent in a Randomized Trial of Adjunctive Ketamine for Alcohol Use Disorder: Secondary Analysis of the KARE Trial 2026 post hoc secondary analysis of RCT 96 Supports Ketamine plus mindfulness-based support gave 78.5% versus 57.8% days abstinent over weeks 17-24 and a 55% relative reduction in heavy drinking days, though the no-heavy-drinking-days difference was not significant.
Ketamine for substance use disorders: a systematic review and meta-analysis 2026 systematic review and meta-analysis 798 Mixed Across 15 RCTs, ketamine improved abstinence at less than one month (OR 3.27) but not at one to six months (OR 1.74, non-significant), with no significant differences in dropout or adverse events.
Targeting craving with ketamine treatment in substance use disorders : a systematic review and meta-analysis 2026 systematic review and meta-analysis 389 Supports Across 11 RCTs, ketamine was associated with a significant reduction in craving (Hedges g=0.34) and increased likelihood of abstinence versus control.
Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review 2021 systematic review Mixed Reviews and meta-analyses support robust, rapid, transient antidepressant and anti-suicidal effects, while evidence for other indications such as substance use is less established.
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 appear promising for substance use disorders, but solid evidence for benefit in addiction is still lacking.
Treating addiction with an addictive drug: the ketamine paradox revisited 2026 narrative review Mixed Ketamine combined with psychotherapy shows promising craving reductions and increased abstinent days in small-to-moderate phase 2 trials for alcohol and cocaine use disorders, but relapse-prevention effects are inconsistent and misuse risk is well established.
Novel pharmacotherapies for opioid use disorder and opioid withdrawal 2026 narrative review Mixed Ketamine has preliminary randomized evidence for effects on abstinence, withdrawal, craving, and psychotherapy augmentation in opioid use disorder, but controlled evidence is limited.
Adjunctive ketamine for affective symptoms, craving, and relapse prevention in opioid use disorder: protocol for a randomised, double-blind, placebo-controlled clinical trial 2026 clinical protocol Unclear Describes a planned double-blind placebo-controlled trial of adjunctive ketamine (0.5 mg/kg, six infusions) on depressive symptoms and relapse-associated outcomes in opioid use disorder; no results yet.
Ketamine use: a review 2011 systematic review Opposes Chronic frequent ketamine use is associated with ulcerative cystitis, working and episodic memory deficits, and addiction concerns, with many users reporting failed attempts to stop.
Brain damages in ketamine addicts as revealed by magnetic resonance imaging 2014 observational cohort 21 Opposes Chronic ketamine addiction was associated with cortical atrophy and lesions in frontal, parietal, and occipital regions appearing 2-4 years after addiction onset.
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 alcohol, opioid, and other substance use disorder categories.
Prescribing bias and adverse outcomes of esketamine in major depression comorbid substance. 2026 retrospective cohort 30670 Opposes Esketamine users had higher risks of comorbid substance use disorder than antidepressant or rTMS patients, and comorbid substance use disorder was associated with higher risks of self-harm, suicide attempt, hospitalization, and mortality.
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, but efficacy declined rapidly with repeated administration.
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder 2018 narrative review Unclear A positive family history of alcohol use disorder was among the most replicated pretreatment predictors of antidepressant response to ketamine in treatment-resistant depression.
Family history of alcohol dependence and antidepressant response to an N‐methyl‐D‐aspartate antagonist in bipolar depression 2012 post hoc analysis of pooled RCTs 33 Supports A positive family history of alcohol dependence predicted greater and more sustained antidepressant response to ketamine in bipolar depression.

Points of agreement

  • Multiple RCTs in alcohol, cocaine, and heroin use disorders report that subanesthetic ketamine combined with psychological therapy reduces use, craving, or relapse versus active or low-dose controls.
  • Craving reduction is the most consistently replicated outcome, supported by meta-analysis and by mediation analyses.
  • The therapeutic effect appears linked to ketamine's psychedelic or mystical-type subjective effects rather than dissociation.
  • Meta-analytic pooling finds a clear short-term abstinence benefit but a non-significant effect at one to six months.
  • Ketamine carries established misuse liability and harms with chronic frequent use, including cystitis, cognitive deficits, and brain changes.

Conflicts

  • Individual trials report large abstinence advantages at one to two years, while pooled meta-analysis finds no significant abstinence benefit beyond one month.
  • The largest placebo-controlled alcohol trial found more abstinent days but no significant difference in relapse rates.
  • Some analyses find family history of alcohol use disorder predicts or moderates greater ketamine response, while the multiple-session heroin trial found no group differences in craving or mood.
  • Reviews range from calling the addiction evidence promising to concluding solid evidence is still lacking.

Gaps

  • Durability beyond six months is poorly established, with the strongest long-term abstinence data coming from small single-site trials.
  • Most trials are small phase 2 studies with heterogeneous dosing, comparators, and follow-up periods.
  • Blinding integrity and the contribution of psychedelic expectancy are not well characterized.
  • Opioid use disorder has only preliminary and protocol-stage evidence.
  • Safety in repeated dosing and in patients with comorbid substance use disorder is insufficiently characterized.
  • Animal data suggest rapid tolerance to ketamine's alcohol-suppressing effect, which is unstudied clinically.
Browse these studies in the library

Common questions

What does the research agree on about ketamine for addiction?
  • Multiple RCTs in alcohol, cocaine, and heroin use disorders report that subanesthetic ketamine combined with psychological therapy reduces use, craving, or relapse versus active or low-dose controls.
  • Craving reduction is the most consistently replicated outcome, supported by meta-analysis and by mediation analyses.
  • The therapeutic effect appears linked to ketamine's psychedelic or mystical-type subjective effects rather than dissociation.
  • Meta-analytic pooling finds a clear short-term abstinence benefit but a non-significant effect at one to six months.
  • Ketamine carries established misuse liability and harms with chronic frequent use, including cystitis, cognitive deficits, and brain changes.
Where do studies on ketamine for addiction conflict?
  • Individual trials report large abstinence advantages at one to two years, while pooled meta-analysis finds no significant abstinence benefit beyond one month.
  • The largest placebo-controlled alcohol trial found more abstinent days but no significant difference in relapse rates.
  • Some analyses find family history of alcohol use disorder predicts or moderates greater ketamine response, while the multiple-session heroin trial found no group differences in craving or mood.
  • Reviews range from calling the addiction evidence promising to concluding solid evidence is still lacking.
What is still unknown about ketamine for addiction?
  • Durability beyond six months is poorly established, with the strongest long-term abstinence data coming from small single-site trials.
  • Most trials are small phase 2 studies with heterogeneous dosing, comparators, and follow-up periods.
  • Blinding integrity and the contribution of psychedelic expectancy are not well characterized.
  • Opioid use disorder has only preliminary and protocol-stage evidence.
  • Safety in repeated dosing and in patients with comorbid substance use disorder is insufficiently characterized.
  • Animal data suggest rapid tolerance to ketamine's alcohol-suppressing effect, which is unstudied clinically.
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

143 articles · 64 from the last two years · 355,042 participants across 57 studies reporting sample size

Common study designs

review 30 case study 8 systematic review 12 experimental study 9 randomized controlled trial 17

Research volume by year

Compare topics →

139 studies whose primary subject is ketamine for addiction since 2002

Studies about ketamine for addiction per year, 2002 to 2026, peaking at 36 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 36 in 2025
Year Studies
2002 2
2003 0
2004 0
2005 0
2006 0
2007 1
2008 0
2009 0
2010 0
2011 3
2012 1
2013 1
2014 5
2015 2
2016 0
2017 3
2018 5
2019 6
2020 3
2021 6
2022 13
2023 8
2024 19
2025 36
2026 25

Research

Synthesize the evidence →

Ketamine, an interoceptive associative agent? Evidence from ketamine-assisted Mindfulness-Oriented Recovery Enhancement for opioid use disorder

Journal of Psychopharmacology November 5, 2026 Benjamin R. Lewis, Eric L Garland

Background: Relapse in opioid use disorder (OUD) remains common despite pharmacotherapy. Altered interoceptive processing may contribute to addiction, and ketamine-induced changes in salience and insula-related networks may facilitate mindfulness-based interoceptive learning. Aims: This secondary analysis examined whether ketamine-assisted psychotherapy (KAP) added to Mindfulness-Oriented...

DOI: 10.1177/02698811261495546 (opens in new tab)

Adjunctive ketamine for affective symptoms, craving, and relapse prevention in opioid use disorder: protocol for a randomised, double-blind, placebo-controlled clinical trial

BMC Psychiatry October 16, 2026 Morfeas Koumas, Markos Apostolakis, Evanthia Bella et al.

Abstract Background Opioid use disorder (OUD) is a chronic relapsing condition associated with substantial mortality. Although medications for opioid use disorder (MOUD) can be effective in reducing opioid use and improving treatment outcomes, relapse to drug use remains common, highlighting the need for adjunctive interventions that address relapse-relevant symptoms not fully targeted by MOUD...

DOI: 10.1186/s12888-026-08628-3 (opens in new tab)

Mechanisms of anti-depressant and anti- alcohol effects of ketamine in patients with alcohol use disorder

Research Square September 30, 2026 Merve Mollaahmetoglu, Joy Krecké, Charlie Oldfield et al. preprint

Abstract Ketamine is known to have anti-depressant effects and is suggested to reduce substance use. However, little is known about the mechanism of these effects. Given evidence from studies in depression of a greater therapeutic effect in those with a family history of AUD, this latter factor was also investigated as a moderating factor. We used data from the KARE trial, a randomised...

DOI: 10.21203/rs.3.rs-11194569/v1 (opens in new tab) Full text (opens in new tab)

No Heavy Drinking Days and Percentage of Days Abstinent in a Randomized Trial of Adjunctive Ketamine for Alcohol Use Disorder: Secondary Analysis of the KARE Trial

medRxiv September 28, 2026 Celia J. A. Morgan, David Nutt preprint

In the KARE trial, 96 adults with severe alcohol use disorder, abstinent following detoxification, were randomised in a 2×2 factorial design to 3 weekly infusions of ketamine (0.8 mg/kg) or saline, each combined with mindfulness-based psychological support (PS) or alcohol psychoeducation (PE). We re-expressed the trial data on endpoints acceptable to regulators and compared the most and least...

DOI: 10.64898/2026.09.26.26363761 (opens in new tab) Full text (opens in new tab)

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 Addiction With Multisystem Toxicity: A Case Report From Canon Lan Detox Unit, Neath Port Talbot Hospital, South Wales

BJPsych Open June 1, 2026 Emeka Onochie, Saminathan Anand, Collins Esiwe et al.

Aims: Ketamine misuse is an emerging public health concern, with increasing reports of severe physical and psychological complications. Chronic use is associated with hepatobiliary and urinary tract injury, often linked to ketamine’s metabolic pathways and toxicological effects (1-3). This report describes the complications and treatment outcomes of a young adult with severe ketamine dependence...

DOI: 10.1192/bjo.2026.11874 (opens in new tab) Full text (opens in new tab)

Clinical trials

All ketamine for addiction trials →