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Home/Research/Ketamine/Substance Use Disorders (SUD)

Ketamine for Substance Use Disorders (SUD)

68 papers and 38 clinical trials exploring ketamine as a treatment for substance use disorders (sud).

CompoundArylcyclohexylamine

Ketamine

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

Full Ketamine profile
IndicationAmong the world’s largest preventable health burdens

Substance Use Disorders (SUD)

Addiction is one of the oldest hopes for psychedelic medicine, going back to LSD trials for alcoholism in the 1950s. Today psilocybin is the workhorse, with positive trials in alcohol, tobacco and cocaine use disorders, and the cross-substance signal is real. But the picture is mixed rather than settled: a major alcohol trial was null, the studies are small, and almost all of them struggle to keep patients unaware of whether they got the drug. This page is the hub; alcohol, opioid and tobacco use disorders have their own dedicated pages.

Full Substance Use Disorders (SUD) profile

Academic Research

68 papers
Open Accessindividual

Effects of a Single Sub-Anesthetic Dose of Ketamine in Tobacco Use Disorder: An Active-Placebo, Randomized Crossover Study

This randomised crossover study (n=18) tested a single sub-anesthetic ketamine infusion against midazolam in adults with tobacco use disorder who were not trying to quit smoking. Ketamine was well tolerated but did not clearly reduce smoking, craving or withdrawal, although some participants reported stronger psychological effects and found abstaining easier afterwards.

Published
April 30, 2026
Journal
Brain Sciences
Authors
Luzum, N. R., McCall, M. H., Talley Boyd, C., Columbano, H., Ip, E., Saldana, S., Oliveto, A. H., Addicott, M.
Paywallindividual

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.

Published
October 13, 2025
Journal
ACS Chemical Neuroscience
Authors
Agrawal, R., Gillie, D., Mungenast, A., Chytil, M., Engel, S., Wu, M. C., Rasmussen, K., Salinas, E., Olson, D. E.
Paywallindividual

Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval

This real-world safety analysis of esketamine in the United States (n=58,483 patients, 1,486,213 treatment sessions over 58 months) found that sedation, dissociation, and increased blood pressure occurred in 34.7%, 41.0%, and 0.9% of sessions respectively, with serious adverse events in <0.1-0.18% of sessions, suicide rates lower than background rates, and 210 cases of abuse/misuse reported, confirming the established safety profile with no new safety signals identified.

Published
October 1, 2025
Journal
American Journal of Psychiatry
Authors
Sanacora, G., Ahmed, M., Brown, B., Cabrera, P., Doherty, T., Himedan, M., Kern, D. M., Lim, L., Lopena, O., Naranjo, R. R., Nuamah, I., Sarayani, A., Turkoz, I., Bowrey, H. E.
Paywallindividual

Efficacy and safety of esketamine for smoking cessation among patients diagnosed with lung cancer and major depression disorder: A randomized, placebo-controlled clinical trial

This multicenter, randomised, placebo-controlled clinical trial (n=236) investigates the efficacy and safety of esketamine (ESK) (8x35mg) for smoking cessation in patients with lung cancer and major depressive disorder (MDD). Eight weekly intranasal ESK sessions significantly improved both self-reported (44.1%) and biologically verified (28.8%) smoking abstinence at 6-month follow-up, alongside reductions in depression, anxiety, nicotine dependence, and respiratory symptoms.

Published
August 1, 2025
Journal
Journal of Affective Disorders
Authors
Hong, C. J.
Open Accessmeta

Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome

This meta-analysis (2024, s=31) examines the correlation between subjective effects and therapeutic outcomes for ketamine (s=23, n=471) and psilocybin (s=8, n=183) in depression and substance use disorder (SUD) treatment. It finds modest mediating effects of subjective experiences on therapeutic outcomes, with psilocybin showing a stronger mediating effect (R² = 24%) compared to ketamine (R² = 5-10%), and a greater mediating effect observed in SUD compared to depression regardless of the substance used.

Published
October 6, 2024
Journal
npj Mental Health Research
Authors
Dahan, J. D. C., Dadiomov, D., Bostoen, T., Dahan, A.
Open Accessindividual

Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems

In a double-blind, randomised pilot study of 28 people with alcohol problems, sublingual esketamine (115.1 mg) combined with two weeks of daily mindfulness-based intervention increased psychological engagement with the practice and produced transient reductions in alcohol craving versus placebo. Esketamine also elicited greater mystical and dissociative experiences, suggesting these altered states may underlie enhanced engagement and potential therapeutic benefit.

Published
June 11, 2024
Journal
Journal of Psychopharmacology
Authors
Gent, E. M., Bryan, J. W., Cleary, M. A., Clarke, T. I., Holmwood, H. D., Nassereddine, R. O., Salway, C., Depla, S., Statton, S., Krecké, J., Morgan, C. J.

Clinical Trials

38 trials
Not yet recruitingPhase II

Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement

This Phase II, randomised, double-blind trial (n=88) will evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) for individuals with opioid use disorder (OUD) receiving medication treatment. The primary aim is to determine whether participants receiving the KetaMORE intervention will show greater reductions in opioid use and craving compared to those receiving ketamine-assisted psychotherapy paired with a non-mindfulness support group. Participants will be randomly assigned to one of two conditions: the experimental group will receive ketamine-assisted psychotherapy alongside Mindfulness-Oriented Recovery Enhancement, while the control group will receive ketamine-assisted psychotherapy with a support group intervention that does not include mindfulness training. Both groups will undergo identical ketamine dosing and psychotherapy sessions, differing only in the adjunctive behavioural intervention. Key outcome measures will include the number of days of opioid use, time to first opioid use lapse, craving levels, and mood, assessed through ecological momentary assessments and standardised measures at various points throughout the study. The trial is set to begin in February 2026 and aims for completion by April 2028.

Started
February 1, 2026
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT07369089
RecruitingPhase II

Ketamine for Opioid Use Disorder

This randomised, quadruple-blind, placebo-controlled Phase II trial (n=50) will assess the effects of ketamine (52.5mg/70kg; 0.75 mg/kg IM, four doses over two weeks) on opioid craving and withdrawal symptoms in adults newly entering methadone treatment for opioid use disorder.

Started
August 1, 2025
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06943859
RecruitingPhase NA

ACT for Alcohol Use Disorder and Depression

This interventional single-group feasibility study (n=20) will assess 8 weekly ACT sessions combined with clinic IV ketamine infusions for adults (18–70) with alcohol use disorder and treatment-resistant depression.

Started
May 1, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06620276
RecruitingPhase II

Ketamine and Neurofeedback as Combined Therapeutic Interventions to Target Glutamatergic Neurotransmission in Alcohol Use Disorder (Nektar)

This Phase II, randomised, placebo-controlled, double-blind, parallel-group single-centre trial (n=75) will assess the effects of a single IV ketamine infusion (0.8 mg/kg) combined with real-time fMRI neurofeedback versus sham NFT and placebo in people with alcohol use disorder.

Started
May 1, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06969937
Active not recruitingPhase II

Ketamine Therapy for Methamphetamine Use Disorder & HIV (KetaMet)

Single-arm pilot feasibility trial (n=12) of intramuscular ketamine (0.50–0.75 mg/kg IM, 3 doses ~once weekly) combined with manualised psychotherapy (7 sessions) for publicly insured patients with moderate-to-severe methamphetamine use disorder who have or are at-risk for HIV.

Started
January 1, 2025
Type
interventional
Blinding
none
Randomized
No
Registry ID
NCT06538285
RecruitingPhase IV

Ketamine-assisted psychotherapy for methamphetamine use disorder

Open-label, non-randomised Phase IV pilot (n=20) evaluating safety and feasibility of manualised 4-session CBT with three adjunctive subcutaneous ketamine doses (weekly, weeks 2–4) for adults with methamphetamine use disorder.

Started
September 2, 2024
Type
interventional
Blinding
none
Randomized
No
Registry ID
ACTRN12624000895583

Explore further

Search all Ketamine papers Search all Substance Use Disorders (SUD) trials Full Ketamine profile Full Substance Use Disorders (SUD) profile