Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review

Abstract

Recently, the abuse of ketamine has soared. Therefore, it is of great importance to study its potential risks. The effects of prolonged ketamine on the brain can be observationally studied in chronic recreational users. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. We searched the following electronic databases: Medline, Embase and PsycINFO We screened 11,438 records and 16 met inclusion criteria, totaling 440 chronic recreational ketamine users (2–9.7 years; mean use 2.4 g/day), 259 drug-free controls and 44 poly-drug controls. Long-term recreational ketamine use was associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity. The observed differences in both structural and functional neuroanatomy between ketamine users and controls may explain some of its long-term cognitive and psychiatric side effects, such as memory impairment and executive functioning. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse.

Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling

“…While these neuropathological rat findings are of unclear significance for human safety, they cannot be discounted. Chronic ketamine abuse has been associated with brain damage and cognitive impairment [ 61 ], and similar effects cannot be excluded when ketamine is used chronically at dissociative doses for MDD treatment. In contrast, esmethadone and racemic methadone do not cause Olney’s lesions in rats [ 62 ].…”

An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome

“…The informed consent procedure included extensive discussion of potential risks of ketamine, including sedation, headache, nausea, elevated blood pressure and heart rate, and perceptual disturbances. 27 While this study involved only a single dose, caregivers were also informed that repeated ketamine use has been associated with structural and functional brain changes, 28 cognitive problems, and increased inflammatory cytokines. 29 Ten participants were screened, and all met criteria for inclusion and were enrolled between August 2020 and May 2021.…”

Effect of Prenatal Ketamine Exposure: A Focused Literature Review

“…The self administration and rapid physiological response make this drug susceptible for misuse among the general population (66). The adverse effects that coincide with misusing ketamine have been explained by the increased dosage used recreationally compared to the clinical dosage (67). Additionally, ketamine has been proven to significantly change the structure and network function within the substantia nigra, ventral tegmental area, and posterior cingulate cortex.…”