Ketamine for Healthy Volunteers

11 papers and 27 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

11 papers
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
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

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
Journal
Clinical Pharmacology and Therapeutics
Authors
Ahmadkhaniha, R., Amanfo, L., Appelbaum, L. G., Avula, S. G. C., Awan, A., Barksdale, C. T., Berrada, K., Bourne, S., Byard, S., Castledine, R., Cogan, G. B., DeLaRosa, J., Gilbert, J. R., Goldfeder, L., Gould, T. D., Gufford, B. T., Guptill, J. T., Jordan, L., Kennedy, M., Kowalski, K,, Lawrence, Q., Lawson, S., Mack, M., McQuaker, S. J., Moaddel, R., Moore, M. C., Morris, P. J., Oxendine, S., Pao, M., Peterson, M., Quigley, P., Radcliffe, J., Raja, S. M., Rich, N., Sancho, A. R., Thomas, C. J., Twieg, R., Wilmshurst, M., Zanos, P., Zarate, C. A., Zuleta, H.
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
Journal
Translational Psychiatry
Authors
Ballard, E. D., Crainiceanu, C. M., Cui, E., Duncan, W. C., Greenstein, D., Hejazi, N. S., Reiss, P. T., Zarate, C. A.
Open Accessindividual

Ketamine and Attentional Bias Toward Emotional Faces: Dynamic Causal Modeling of Magnetoencephalographic Connectivity in Treatment-Resistant Depression

In a double-blind crossover MEG study using dynamic causal modelling during an emotional-face attentional task, a single ketamine infusion rapidly reduced symptoms in treatment-resistant depression and produced region-specific changes in glutamatergic and GABAergic transmission (faster GABA and NMDA in early visual cortex, faster NMDA in fusiform, slower NMDA in amygdala) with altered local inhibition in early visual and inferior frontal cortices. Symptom improvement correlated with faster AMPA transmission and increased gain of spiny stellate cells in early visual cortex, supporting GABA/NMDA inhibition–disinhibition models and emphasising AMPA throughput as a key mediator of ketamine's antidepressant effects.

Published
Journal
Frontiers in Psychiatry
Authors
Galiano, C. S., Gilbert, J. R., Nugent, A. C., Zarate, C. A.

Clinical Trials

27 trials
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
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
12625001087448

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