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Home/Research/Ketamine/Chronic Pain

Ketamine for Chronic Pain

57 papers and 33 clinical trials exploring ketamine as a treatment for chronic pain.

CompoundArylcyclohexylamine

Ketamine

A dissociative anesthetic with rapid-acting antidepressant properties, widely used in clinical settings for mood and pain disorders.

Full Ketamine profile
IndicationOver 1.5 billion worldwide.

Chronic Pain

Chronic pain is increasingly recognised as a multifaceted condition that may respond to psychedelic therapies, which are gaining attention in clinical settings for their potential efficacy in pain management. Recent research indicates that compounds such as psilocybin and MDMA are entering clinical trials aimed at exploring their therapeutic effects on chronic pain syndromes.

Full Chronic Pain profile

Academic Research

57 papers
Paywallindividual

Protocol and pilot results for a double-blind randomized placebo-controlled trial of ketamine under propofol sedation for chronic pain and depression

This randomised, double-blind, placebo-controlled trial protocol and pilot study (n=42) is testing ketamine 0.5 mg/kg given under propofol sedation for chronic pain with depression, with pain as the main outcome. In six pilot participants, there were no serious adverse events and propofol seemed to help mask treatment allocation, although many still guessed ketamine immediately after sedation.

Published
April 16, 2026
Journal
Pain Management
Authors
Lii, T. R., Sikka, P., Deverett, B., Altirkawi, O. K., Heifets, B. D.
Open Accessindividual

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published
February 18, 2026
Journal
JAMA Psychiatry
Authors
Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.
Open Accessmeta

Oral Ketamine for Chronic Pain: Towards an Evidence-Based Dosing Regimen

This systematic review (s=27) of oral ketamine for chronic cancer and non-cancer pain found that mean pain scores fell from 7.72/10 to 3.2/10 over 30 to 90 days, though only 5 studies had sufficient dosing consistency for quantitative analysis, with 35 mg/70kg three times daily identified as an effective regimen with an acceptable safety profile.

Published
February 7, 2026
Journal
Journal of Pain Research
Authors
Winegarden, J., Brose, A., Storm, A., Mortensen, A., Carr, D.
Open Accessindividual

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study

This double-blind Phase IIb trial (n=147) evaluated the efficacy, safety, and tolerability of esketamine nasal spray versus midazolam in reducing depressive (MDD) symptoms in adolescents at imminent risk for suicide (SI). The study finds that pooled doses of esketamine (56 and 84 mg) significantly reduce depressive symptoms at 24 hours, with common side effects including dizziness, nausea, and dissociation.

Published
January 1, 2026
Journal
Journal of the American Academy of Child & Adolescent Psychiatry
Authors
Kosik-Gonzalez, C., Chen, L. N., Lane, R., Bloch, M. H., DelBello, M., Moreno, C., Drevets, W. C., Canuso, C. M., Fu, D. J.
Open Accessindividual

Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

In a phase 4, multicentre, double-blind randomised trial in adults with treatment‑resistant depression, intranasal esketamine monotherapy (56 mg and 84 mg) produced significant reductions in MADRS score versus placebo at day 28 (LS mean differences −5.1 and −6.8; effect sizes 0.48 and 0.63) and demonstrated rapid benefit at 24 hours. The tolerability profile was consistent with prior reports, most commonly nausea, dissociation, dizziness and headache.

Published
September 1, 2025
Journal
JAMA Psychiatry
Authors
Janik, A., Qiu, X., Lane, R., Popova, V., Drevets, W. C., Canuso, C. M., Macaluso, M., Mattingly, G. W., Shelton, R. C., Zajecka, J. M., Fu, D. J.
Open Accessindividual

Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis

This pharmacovigilance analysis (n=751) examines suspected adverse reactions (SARs) to esketamine nasal spray (Spravato) reported in the EudraVigilance database across European countries. The study identifies increased blood pressure (15.4%) and dissociation (15%) as the most common SARs, with data suggesting a potentially higher risk of suicidality with esketamine compared to fluoxetine and venlafaxine, prompting recommendations for careful monitoring of patients with a history of suicidal ideation.

Published
May 9, 2025
Journal
Pharmaceuticals
Authors
Ammendolia, I., Mannucci, C., Esposito, E., Calapai, G., Currò, M., Midiri, P., Mondello, C., Cardia, L., Calapai, F.

Clinical Trials

33 trials
Not yet recruitingPhase NA

Evaluation of efficacy of ketamine for prevention of chronic pain in patients with Lower Limb amputation.

This randomised, parallel-group, participant- and investigator-blinded active-controlled trial (n=88) in India is assessing strategies to prevent phantom limb pain after lower limb amputation. The study compares a conventional pain management protocol with a multimodal analgesic approach, both including intravenous ketamine infusion at 0.15 mg/kg/hour continued for 48 hours post-operatively. The trial is designed to evaluate whether this perioperative analgesic regimen can reduce the development and severity of chronic pain following amputation. Primary outcomes focus on pain control in the immediate post-operative period and longer-term phantom limb pain. Within 48 hours, the investigators will measure pain severity using the visual analogue scale, opioid consumption, including total dose, number of doses, and time to first rescue analgesia. Phantom limb pain incidence and severity will then be assessed at 1, 3, and 6 months after surgery using the Phantom Pain Questionnaire. The study also includes psychological outcomes measured with the Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale. Secondary outcomes include adverse drug effects and patient satisfaction with pain management. No phase is specified.

Started
April 23, 2026
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
CTRI/2026/04/109150
Not yet recruitingPhase I

The Role of Coadministration of Lidocaine and Ketamine in Opioid-Refractory Chronic Cancer-Related Pain.

This Early Phase I, randomised, double-blinded, placebo-controlled, cross-over trial (n=24) will evaluate the efficacy of intravenous infusions of lidocaine and ketamine in patients suffering from opioid-refractory chronic cancer-related pain. Participants will receive two infusions, spaced one week apart, consisting of lidocaine at 4 mg/kg and ketamine at 0.2 mg/kg, compared to an active placebo of midazolam at 0.02 mg/kg. The primary aim is to determine whether the lidocaine-ketamine regimen provides superior analgesia compared to the placebo. The trial will assess various outcomes, including pain intensity and physical functioning using the Brief Pain Inventory (BPI), emotional functioning via the Beck Depression Inventory (BDI), and overall improvement through the Patient Global Impression of Change (PGIC) scale. Additionally, total opioid consumption will be measured in oral morphine equivalents, and neuropathic pain effects will be evaluated using the Neuropathic Pain Symptom Inventory (NPSI). Eligible participants are adults aged 18 years or older with moderate to severe cancer-related pain despite optimised analgesic therapy. The study is set to begin in March 2026 and is expected to conclude by August 2027.

Started
March 1, 2026
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT07408193
Not yet recruitingPhase III

Optimal Timing of Ketamine Initiation for SCD Pain

This Phase III, randomised, triple-masked, parallel-group trial (n=90) will evaluate whether a single early oral dose of ketamine 0.5mg/kg (max dose of 35mg) given within 1 hour of presentation reduces the proportion of 6–24-year-olds with sickle cell disease presenting with acute pain who are admitted to hospital. The primary outcome is the percentage of participants admitted from the emergency department or infusion clinic within 6 hours of presentation. Participants are randomised to oral ketamine or placebo; the ketamine study drug is prepared from ketamine hydrochloride injection compounded into an oral solution and administered with taste-masking (either a Listerine strip before and after dosing or mixed with cherry syrup), while placebo is matching sterile water with the same masking. If participants are admitted, they may start open-label intravenous ketamine per clinical need and those who receive inpatient ketamine will be reviewed to assess effects on opioid use and hospital length of stay. Key eligibility includes a diagnosis of sickle cell disease, presentation with pain to ED or infusion clinic, age 6–24 years, and no ketamine allergy or contraindicating history. The study is planned to start in February 2026 with estimated completion in February 2030.

Started
February 1, 2026
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT07450430
Not yet recruitingPhase II

Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression

This Phase II, open‑label, single‑group trial (n=25) will evaluate ketamine‑assisted psychotherapy in adults with treatment‑resistant depression (including participants with chronic pain) to assess feasibility, antidepressant effect and frontolimbic brain plasticity using functional MRI. The intervention is intramuscular ketamine hydrochloride (0.5–1 mg/kg IM, capped at 60 mg), given as 1–2 dosing sessions paired with psychotherapy; primary outcomes include proportion retained through 2‑month follow‑up and mean change in Hamilton Depression Rating Scale (HDRS) scores. Participants will attend 6–8 visits including two MRI scans (baseline and follow‑up), 3–4 psychotherapy sessions (two preparatory sessions before the first ketamine), and 1–2 supervised IM ketamine sessions (visit 4: 0.5 mg/kg not to exceed 60 mg; visit 6: dose may be increased but will not exceed 60 mg, determined by investigators). Supportive medications (ondansetron, lorazepam, clonidine) are available for nausea, agitation or hypertension. Key eligibility includes age ≥18, HDRS in the moderate or above range and failure of two adequate antidepressant trials in the past two years; standard MRI and medical exclusions (cardiac, uncontrolled hypertension, recent substance‑use criteria, pregnancy, etc.) apply. HDRS assessments are scheduled at baseline, within 90 minutes after dosing, daily for up to 7 days around baseline and dosing, and at the 2‑month follow‑up.

Started
January 1, 2026
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT07247006
Not yet recruitingPhase II

Safety and Efficacy of Lidocaine Versus Ketamine Infusion for Resistant Orofacial Pain

This Phase II, randomised, quadruple-masked, parallel trial (n=105) will evaluate the safety and efficacy of intravenous lidocaine, ketamine and a combined lidocaine–ketamine infusion in adults with treatment-resistant orofacial pain, with the primary outcome of pain reduction measured by the Visual Analog Scale (VAS). Interventions are lidocaine 5 mg/kg (max 500 mg) infused over 4 hours, ketamine 0.3 mg/kg infused over 4 hours, and a combined infusion of lidocaine 2.5 mg/kg plus ketamine 0.15 mg/kg infused over 4 hours. Participants will be randomised equally into three arms and receive their assigned slow intravenous infusion once weekly for three consecutive weeks with continuous cardiovascular and neurological/CNS monitoring during and after each infusion. Efficacy assessments occur at baseline, prior to the 2nd and 3rd infusions, and at 1, 3 and 6 months post-treatment; secondary measures include cortisol changes, depression assessment using PLAT‑Q and adverse event monitoring. Adults over 18 with orofacial pain refractory to standard therapies (including trigeminal neuralgia, TMJ dysfunction, malignant otitis externa, migraine or atypical facial pain) are eligible, and planned analyses include one-way ANOVA and repeated measures ANOVA for continuous outcomes.

Started
January 1, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07250867
Not yet recruitingPhase I/II

Ketamine Assisted Psychotherapy for Treating Comorbid Chronic Pain and PTSD

Open-label, randomised, parallel pilot RCT (n=30) comparing ketamine (0.5 mg/kg IV x4 over 2 weeks) plus MBCT versus MBCT alone for adults with comorbid chronic pain and PTSD.

Started
October 1, 2025
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
NCT07009158

Explore further

Search all Ketamine papers Search all Chronic Pain trials Full Ketamine profile Full Chronic Pain profile