Chronic ketamine use increases serum levels of brain-derived neurotrophic factor

Ketamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids (EAAs) including glutamate and aspartate. The use of ketamine at subanaesthetic doses has increased because of its psychotomimetic properties. However, long-term ketamine abuse may interfere with memory processes and inhibit the induction of long-term potentiation (LTP) in the hippocampus, an effect probably mediated by its NMDA antagonist action. Neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as survival factors for selected populations of central nervous system neurons, including cholinergic and dopaminergic neurons. In addition, neurotrophins, particularly BDNF, may regulate LTP in the hippocampus and influence synaptic plasticity. The purpose of this study was to test the hypothesis that ketamine use in humans is associated with altered serum levels of neurotrophins. We measured by enzyme-linked immunosorbent assay the NGF and BDNF serum levels in two groups of subjects: frequent ketamine users and healthy subjects. Our data show that BDNF serum levels were increased in chronic ketamine users as compared to healthy subjects, while NGF levels were not affected by ketamine use. These findings suggest that chronic ketamine intake is associated with increases in BDNF serum levels in humans. Other studies are needed to explore the pharmacological and molecular mechanism by which ketamine, and/or other NMDA antagonists, may induce modification in the production and utilization of BDNF and alter normal brain function.