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Home/Research/Ketamine/Healthy Volunteers

Ketamine for Healthy Volunteers

38 papers and 28 clinical trials exploring ketamine as a treatment for healthy volunteers.

CompoundArylcyclohexylamine

Ketamine

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

Full Ketamine profile
IndicationApproximately 300 million people affected by depression worldwide.

Healthy Volunteers

Research involving healthy volunteers has expanded to investigate the therapeutic potentials of various psychedelics for mental health conditions. Recent findings, emphasizing compounds like psilocybin and DMT, illustrate a promising future for psychedelic-assisted therapies.

Full Healthy Volunteers profile

Academic Research

38 papers
Open Accessindividual

Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach

This brain imaging study (n=11) found that a single intravenous dose of ketamine (70mg/70kg) increased glutamate levels in the anterior cingulate cortex and altered functional connectivity between this region, the dlPFC, and the amygdala in healthy men. Multimodal imaging also suggested that ketamine-related increases in a putative marker of synaptic plasticity were linked to reduced default mode network activity.

Published
March 21, 2026
Journal
Journal of Cerebral Blood Flow and Metabolism
Authors
Agnorelli, C., Peill, J., Sawicka, G., Kurtin, D., Shatalina, E., Ahmad, K., Wall, M. B., Rua, C., Godfrey, K., Ertl, N., Searle, G., Zhou, K., Osugo, M., Weiss, B., Greenway, K. T., Fagiolini, A., Carhart-Harris, R., Matthews, P. M., Rabiner, E. A., Nutt, D., Erritzoe, D.
Open Accessindividual

The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression

Using the PET tracer [11C]K-2 to image AMPAR density in vivo, the authors found that lower AMPAR availability correlates with greater illness severity and differs between patients with treatment‑resistant depression and healthy controls. Ketamine produced region‑specific changes in AMPAR density that correlated with clinical improvement and partially restored the abnormal AMPAR phenotype, supporting AMPAR dynamics as a mechanistic substrate of ketamine’s antidepressant effect in TRD.

Published
March 5, 2026
Journal
Molecular Psychiatry
Authors
Nakajima, W., Hatano, M., Ohtani, Y., Tani, H., Yatomi, T., Tsuchimoto, S., Fujimoto, Y., Eiro, T., Ichijo, S., Nakano, K., Arisawa, T., Takada, Y., Kimura, K., Abe, H., Sano, A., Nomoto-Takahashi, K., Yonezawa, K., Tomiyama, S., Nagai, N., Kusudo, K., Honda, S., Moriyama, S., Nakajima, S., Yamada, T., Iwabuchi, Y., Jinzaki, M., Yoshimura, K., Syed, S. A., Tsugawa, S., Uchida, H., Takahashi, T.
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 Accessindividual

A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers

In a Phase 1 single- and multiple-ascending IV dosing study in healthy volunteers, (2R,6R)-hydroxynorketamine was well tolerated with minimal adverse events, showed no anesthetic or dissociative effects and demonstrated dose-proportional pharmacokinetics with confirmed CNS exposure in CSF. Quantitative EEG showed increases in gamma power in some participants, supporting progression of RR‑HNK into Phase 2 development.

Published
July 25, 2024
Journal
Clinical Pharmacology and Therapeutics
Authors
Raja, S. M., Guptill, J. T., Mack, M., Peterson, M., Byard, S., Twieg, R., Jordan, L., Rich, N., Castledine, R., Bourne, S., Wilmshurst, M., Oxendine, S., Avula, S. G. C., Zuleta, H., Quigley, P., Lawson, S., Mcquaker, S. J., Ahmadkhaniha, R., Appelba, L. G., Kowalski, K., Barksdale, C. T., Gufford, B. T., Awan, A., Sancho, A. R., Moo, M. C., Berrada, K., Cogan, G. B., Delarosa, J., Radcliffe, J., Pao, M., Kenne, M., Lawrence, Q., Goldfeder, L., Amanfo, L., Zanos, P., Gilbert, J. R., Morr, P. J., Moaddel, R., Gould, T. D., Zarate, C. A., Thomas, C. J.
Open Accessindividual

Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression

In a randomized, double-blind crossover study of 36 people with treatment-resistant depression (TRD) and 25 healthy volunteers, ketamine altered the temporal dynamics of sleep EEG spectral power in TRD—producing earlier-night increases in delta power and later-night increases in alpha and delta. These spectral changes occurred without effects on sleep macroarchitecture (e.g. WASO, TST, REM latency), did not mediate ketamine’s antidepressant or anti‑suicidal effects, and baseline TRD showed lower total sleep time and shorter REM latency.

Published
June 4, 2024
Journal
Translational Psychiatry
Authors
Ballard, E. D., Greenstein, D., Reiss, P. T., Crainiceanu, C. M., Cui, E., Duncan, W. C., Hejazi, N. S., Zarate, C. A.
Open Accessindividual

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures

This single-blind placebo-controlled study (n=40) investigated the neural and behavioral effects of acute ketamine in healthy participants. Results revealed robust inter-individual variability in both neural and behavioral responses to ketamine, with data-driven individual symptom variation mapping onto distinct neural gradients. These findings emphasize the need to consider individual variation in response to ketamine and suggest potential implications for developing precise pharmacological biomarkers in psychiatry.

Published
April 17, 2024
Journal
eLife
Authors
Moujaes, F., Lisa, J., Rahmati, M., Burt, J. B., Schleifer, C., Adkinson, B. D., Savic, A., Santamauro, N., Tamayo, Z., Diehl, C., Kolobaric, A., Flynn, M., Rieser, N., Fonteneau, C., Camarro, T., Xu, J., Cho, Y., Repovs, G., Fineberg, S. K., Morgan, P. T., Seifritz, E., Vollenweider, F. X., Krystal, J. H., Murray, J. D., Preller, K. H., Anticevic, A., Vollenweider

Clinical Trials

28 trials
Not yet recruitingPhase II

Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers

This Phase II, randomised, double-blind, placebo-controlled crossover trial (n=92) will evaluate the analgesic potential of a single intravenous infusion of (2R,6R)-hydroxynorketamine (HNK) in healthy adults aged 18 to 60 years. The study will assess whether 0.5 mg/kg HNK reduces acute experimental pain during quantitative sensory testing (QST) and will also examine pain-related and emotion-related brain responses. Participants will receive HNK or matched placebo as a single intravenous infusion over approximately 40 minutes, with visits repeated 1 to 3 weeks apart in the treatment group. A no-treatment control arm is included to help estimate natural changes and placebo effects. Pain ratings, blood draws, and functional MRI assessments will be repeated before and after infusion, including follow-up measures immediately after treatment, at 4 to 5 hours, and one day later. The trial will also compare placebo with the no-treatment group to gauge placebo analgesia.

Started
June 15, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07504601
Not yet recruitingPhase NA

Neural Mechanisms of Ketamine Antidepressant Treatment 2.0: Exploring how ketamine affects the brain function in people with difficult-to-treat depression.

This is a randomised, quadruple‑blind, placebo‑controlled mechanistic clinical trial enrolling 90 participants (60 adults with major depressive disorder, including treatment‑resistant cases, and 30 healthy controls) at the Royal Melbourne Hospital, Australia, with recruitment from February 2026 and completion expected December 2027. Participants receive a single subcutaneous administration of ketamine 0.75 mg/kg versus placebo (0.9% saline). The primary outcome is change in habenula activity measured using ultra‑high‑field 7T MRI at baseline and 24–48 hours after dosing, designed to probe rapid neural mechanisms underlying ketamine’s antidepressant effects. Secondary outcomes assess clinical and behavioural effects using the Montgomery–Åsberg Depression Rating Scale (MADRS), QIDS‑C, Snaith–Hamilton Pleasure Scale (SHAPS), GAD‑7, and objective activity monitoring by actigraphy. The protocol includes healthy controls to facilitate mechanistic comparisons between clinical and non‑clinical neural responses. The study phase is not specified in the available data. The quadruple‑blind design and saline comparator aim to isolate drug‑specific neural changes and early clinical signal following a single subcutaneous ketamine exposure in treatment‑resistant and broader MDD populations.

Started
February 2, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
ACTRN12625001087448
RecruitingPhase I

Investigation of Psychedelic Effects in Psychoactive Substances

Triple-blind, placebo-controlled, within-subjects study (n=50) testing whether various psychoactive substances (psilocybin, ketamine, DXM, DMT, MDMA, THC) produce experiences similar to classic psychedelics across up to six single-dose sessions.

Started
February 5, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06772753
Not yet recruitingPhase I

A study comparing two formulations of R-107 under fasting conditions

Phase I randomised, blinded crossover PK/bioavailability study (n=34) comparing R-107-H (3×60 mg) versus R-107-P (3×60 mg) in healthy volunteers under fasting conditions.

Started
October 9, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
ACTRN12624001308583
RecruitingPhase IV

Pharmacology of human decision making – Study of the effects of ketamine on healthy volunteers (18-55) making simple perceptual decisions

This Phase IV, placebo-controlled crossover trial (n=35) will investigate the impact of ketamine on perceptual decision-making in healthy volunteers.

Started
June 14, 2024
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
ACTRN12624000943549
CompletedPhase I

Acute Analgesic Effects of DMT on Experimentally Induced Pain in Healthy Participants

This randomised, triple-blind, placebo-controlled crossover trial (n=18) will investigate the acute analgesic (anti-pain) effects of N,N-dimethyltryptamine (DMT) on experimentally induced acute nociceptive pain, hyperalgesia, and allodynia in healthy participants.

Started
May 1, 2024
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06180759

Explore further

Search all Ketamine papers Search all Healthy Volunteers trials Full Ketamine profile Full Healthy Volunteers profile