Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5–12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2–4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine.
The results of lesions observed in all the 21 ketamine addicts were depicted in Table Table2.2. Those who had two or less regions in the brain with lesions were classified as light damage. Those that had three to four regions in the brain with lesions were classified as moderate damage, and those with five or more regions with lesions were classified as severe damage. The MRI lesions initially were observed as hyperintense spots (holes or patches) of degeneration in the superficial white matter of the cortex which appeared as early as 1 year after ketamine addiction (Figure (Figure1A),1A), while each lesions spread to the internal capsule by 3 years of addiction (Figure (Figure1B).1B). Slightly after, patches of hyperintense degeneration spots appeared in the basal forebrain (Figure (Figure2A),2A), cerebellum, and pons (Figure (Figure2B),2B), and diencephalon at 4 years of addiction (Figure (Figure2C).2C). Likewise, diffusion blockage was illustrated by FLAIR image in the parahippocampal gyrus and insula, also by 4 years of addiction (Figure (Figure3A),3A), while atrophy of the parahippocampal gyrus was observed a bit later by 5 years of addiction (Figure (Figure3B).3B). Atrophy of the other parts of cortex was first noted after 4 years of addiction, usually with atrophy on only a small region of the cortex (Figure (Figure4)4) and extended to two or three regions (usually frontal, parietal, and occipital) of the cortex by 7 years of addiction (Figure (Figure5).5). Hyperintense lesions were also observed in the corpus striatum by 6 years (Figure (Figure6).6). In this patient cohort, one patient had a combination of drugs and was taking ketamine together with amphetamine and ecstasy. He demonstrated early atrophy of cortex after taking the three drugs together in 0.5 years, in which the basal prefrontal gyrus rectus already exhibited significant atrophy (Figure (Figure7A)7A) when compared with control (Figure(Figure7B).7B). Similarly, cortical atrophy also occurred early in another patient who had used a high dose of ketamine, in this case 3 g per day for 3 years (Figure (Figure8).8). After 7 years of addiction, in all other patients, lesions then appeared in the midbrain (Figure (Figure9).9). From 10 to 12 years of addiction, all lesion sites were as those described above.