Widespread reductions in cortical thickness following ketamine abuse.
Jinsong Tang, Qiuxia Wu, Chang Qi, An Xie, Jianbin Liu, Yunkai Sun, Tifei Yuan, Wei Chen, Tieqiao Liu, Wei Hao, Xu Shao, Yanhui Liao
Journal of Psychiatry and Neuroscience 2024 DOI: 10.1503/jpn.230111 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cross-sectional study Longitudinal Peer reviewed |
|---|---|
| Sample size | 264 |
| Population | Patients with ketamine use disorder and drug-free healthy controls |
| Topics | Ketamine Esketamine |
| Keywords | Drug-abuse Brain-structure Cognitive-health |
| Citations | 7 |
| Key findings | Chronic ketamine users had widespread decreased cortical thickness compared with healthy controls, with no areas of increased thickness observed. |
Abstract
Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.
Comparable studies
Other cross-sectional and survey studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 5-Year Trends in Use of Hallucinogens and Other Adjunct Drugs among UK Dance Drug Users People who use drugs in dance contexts | 2006 | Repeated-measures cross-sectional survey | |
| Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia Healthy subjects, ketamine abusers, and schizophrenia patients | 2014 | Cross-sectional study | n = 998 |
| Ketamine as a primary predictor of out-of-body experiences associated with multiple substance use Online survey respondents | 2011 | Cross-sectional survey | n = 192 |
| Self-reported prevalence of dependence of MDMA compared to cocaine, mephedrone and ketamine among a sample of recreational poly-drug users Global non-treatment-seeking sample of last year users of MDMA, cocaine, mephedrone,... | 2014 | Cross-sectional survey | |
| Near-Death States Reported in a Sample of 50 Misusers Previous ketamine misusers who reported a ketamine-related near-death experience | 2010 | Cross-sectional survey | n = 50 |
Citations in the library
Cited by 6
- The diverse effects of ketamine, jack-of-all-trades: a narrative review. British Journal of Anaesthesia March 1, 2025
- Prophylactic Ketamine: Current Knowledge and Future Directions. Biological Psychiatry March 28, 2025
- Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges Frontiers in Psychiatry October 1, 2026
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review Research Square May 27, 2026
- Repeated 7-day exposure to ketamine induces anxiety-like behaviors and neuronal apoptosis in mice via DRD1-medicated inhibition of Akt/Gsk-3β phosphorylation. Cell Biology and Toxicology January 30, 2026
and 1 more in the library
Cites 19
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Ketamine use: a review Addiction July 21, 2011
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
and 14 more in the library