Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention.
Verner J Knott, Anne M Millar, Judy F McIntosh, Dhrasti K Shah, Derek J Fisher, Crystal M Blais, Vadim Ilivitsky, Ed Horn
Biological Psychology July 13, 2011 DOI: 10.1016/j.biopsycho.2011.06.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | 20 smokers and 20 non-smokers, both male and female, healthy volunteers |
| Interventions | Ketamine Nicotine |
| Dose | 0.04 mg/kg ketamine; 4 mg nicotine gum |
| Measures | P300 event-related brain potential (ERP), visual information processing (RVIP) task |
| Topics | Ketamine Esketamine |
| Keywords | Humans Nicotine Nicotinic agonists Analgesics Drug combinations Electroencephalography Electrooculography Analysis of variance Cross-over studies Double-blind method Photic stimulation Smoking Attention Reaction time Event-related potentials, p300 Dose-response relationship, drug Adolescent Middle aged Female Young adult Surveys and questionnaires |
| Key points | Nicotine improved sustained attention, especially in non-smokers, as measured by performance accuracy and P300 amplitude. Ketamine impaired these behavioral and electrophysiologic measures, and acute nicotine reduced this impairment, with the combined effects differing between smokers and non-smokers. The authors argue these results support nicotinic receptor function as a potential therapeutic target for cognitive deficits in schizophrenia. |
Abstract
Given the cognitive-promoting properties of the nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled nicotine in schizophrenia has been interpreted as an attempt to self-correct cognitive deficits, which have been particularly pronounced in the attentional domain. As glutamatergic abnormalities have been implicated in these attentional deficiencies, this study attempted to shed light on the separate and interactive roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the modulation of attention by investigating, in healthy volunteers, the separate and combined effects of nicotine and the NMDAR antagonist ketamine on neural and behavioural responses in a sustained attention task. In a randomized, double-blind, placebo controlled study, performance and the P300 event-related brain potential (ERP) in a visual information processing (RVIP) task were examined in 20 smokers and 20 non-smokers (both male and female). Assessment involved intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo gum. Nicotine-enhanced attentional processing was most evident in nonsmokers, with both performance accuracy and P300 amplitude measures. Ketamine's detrimental effects on these behavioural and electrophysiologic measures were negatively moderated by acute nicotine, the synergistic effects being expressed differently in smokers and nonsmokers. These findings support the view that acute alterations and individual differences in nAChR function can moderate even subtle glutamatergic-driven cognitive deficiencies in schizophrenia and can be important therapeutic targets for treating cognitive impairments in schizophrenia.
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 5
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
- Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model Current Pharmaceutical Biotechnology June 21, 2018
- Effects of Subanesthetic Ketamine Administration on Visual and Auditory Event-Related Potentials (ERP) in Humans: A Systematic Review Frontiers in Behavioral Neuroscience April 16, 2018
- Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings. Molecular Psychiatry January 14, 2025
- Potential Mechanisms for the Ketamine-Induced Reduction of P3b Amplitudes. Frontiers in Behavioral Neuroscience 2018
Cites 12
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Ketamine activates psychosis and alters limbic blood flow in schizophrenia Neuroreport April 1, 1995
- Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine Archives of General Psychiatry March 1, 2000
and 7 more in the library