A pilot human study using ketamine to treat disorders of consciousness.
Paolo Cardone, Arthur Bonhomme, Vincent Bonhomme, Nicolas Lejeune, Cécile Staquet, Aline Defresne, Naji Alnagger, Pauline Ezan, Minji Lee, Andrea Piarulli, Sebastien Van Goethem, Javier Montupil, Aurore Thibaut, Charlotte Martial, Olivia Gosseries
iScience January 17, 2025 DOI: 10.1016/j.isci.2024.111639 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, cross-over trial Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Adult patients with post-comatose prolonged disorders of consciousness |
| Intervention | Intravenous ketamine |
| Dose | sub-anesthetic concentration, incremental concentrations |
| Duration | During infusion, with continuous EEG recording and assessments |
| Topics | Esketamine Ketamine Philosophy of mind |
| Keywords | Biological sciences Drugs Pharmacology Psychedelic medicine Consciousness research Clinical trials |
| Citations | 9 |
| Key findings | Ketamine infusion increased Lempel-Ziv complexity and reduced spastic paresis and increased arousal, but did not change the explainable consciousness indicator or improve diagnosis. |
Abstract
Post-comatose disorders of consciousness (DoC) represent persistent neurological conditions with limited therapeutic options and a poor prognosis. Recent works advocate for exploring the effects of psychedelics to enhance brain complexity in DoC and ameliorate their consciousness. We investigated sub-anesthetic concentration of the atypical psychedelic ketamine for treating post-comatose prolonged DoC through a double-blind, placebo-controlled, cross-over trial involving three adult patients. Incremental concentrations of intravenous ketamine and saline were administered, alongside continuous electroencephalogram (EEG) recording and assessments of conscious behaviors and spastic paresis. Brain complexity, measured by Lempel-Ziv complexity (LZC) and explainable consciousness indicator (ECI), revealed increased LZC during ketamine infusion but no change in ECI. Patients exhibited reduced spastic paresis and increased arousal as time spent with eyes open but no positive change in diagnosis. No adverse effects were noted. This study contributes to understanding the relationship between consciousness and brain complexity and suggests a potential therapeutic role for ketamine in DoC.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 7
- Pharmacological therapies for early and long-term recovery in disorders of consciousness: current knowledge and promising avenues. Expert Review of Neurotherapeutics June 1, 2025
- Psilocybin for disorders of consciousness: A case-report study. Clinical Neurophysiology May 1, 2025
- The entropic brain today Brain December 12, 2025
- A critical review of brain entropy as a biomarker of the psychedelic state. Neuroscience & Biobehavioral Reviews July 1, 2026
- Acute Effects of Esketamine on the EEG Power Spectrum and Signal Complexity in Prolonged Disorders of Consciousness: A Prospective Exploratory Cohort Study. Journal of neurosurgical anesthesiology June 15, 2026
and 2 more in the library
Cites 20
- A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior Science Translational Medicine August 14, 2013
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Global Street Food: la cocina de la calle Diseño interior 2009
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Scientific Reports April 19, 2017
and 15 more in the library