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Central nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers.

P Hartvig, J Valtysson, K J Lindner, J Kristensen, R Karlsten, L L Gustafsson, J Persson, J O Svensson, I Oye, G Antoni

Clinical Pharmacology & Therapeutics August 1, 1995 DOI: 10.1016/0009-9236(95)90194-9 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, crossover study Peer reviewed
Sample size 5
Population Healthy adult volunteers
Interventions (S)-ketamine (S)-[N-methyl-11C]ketamine
Dose 0, 0.1, and 0.2 mg/kg
Measures positron emission tomography
Topics Ketamine Esketamine
Keywords Brain Humans Pain Tomography, emission-computed Cross-over studies Double-blind method Affect Memory Tissue distribution Dose-response relationship, drug Reference values Adult Middle aged Male
Key points (S)-Ketamine binding in the brain, measured by PET, decreased dose-dependently and correlated with induced analgesia, amnesia, and mood changes. Memory impairment and psychotomimetic effects were consistently seen at plasma (S)-ketamine concentrations above 70 ng/ml and maximum regional brain concentrations above 500 ng/ml, suggesting binding magnitude relates directly to drug effects.

Abstract

Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.

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

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