Table 2.

Structural differences: white matter.

References	N (ketamine vs. control)	Ketamine subjects (ketamine use-other substance use-comorbid disorders)	Controls	Significant differences ketamine subjects compared to controls	Statistic measure	Correlation
Liao et al. (2010)	85 (41–44)	Mean age 26.9 years Male/female 33/8 Mean ketamine use: 2 g/day 3.4 years Ketamine was consumed by snorting 73% Alcohol 68% Ecstasy 66% Amphetamine + caffeine 56% Methamphetamine 20% Marijuana 15% Benzodiazepine 2,4% Heroin 0% Cocaine No history of neurologic disorder or other psychiatric illnesses Excluded if other substance dependence (excl. nicotine)	Drug-free controls Male/female 34/10 Mean age 26.3 years 20% Alcohol	Lower FA in 1) left frontal cortex 2) right frontal cortex 3) left temporoparietal cortex white matter.	1) z= 4.21 (p = 0.014) 2) z=3.96 (p = 0.014) 3) z=3.85 (p = 0.014)	Negative correlation between FA in left (p = 0.015) and right (p = 0.003) frontal white matter and total lifetime consumption(g)
Edward Roberts et al. (2014)	32 (16–16)	Mean age 27.0 years Male/female 9/7 Mean ketamine use: 16.7 g/week 7.3 years Route of administration was not mentioned Regular use: 56% Alcohol 0% MDMA 44% Cannabis 19% Benzodiazepines 38% Cocaine Presence of psychiatric or somatic disorder is not mentioned.	Polydrug controls Mean age 28.5 years Male/female 11/5 Regular use: 75% Alcohol 0% MDMA 50% Cannabis 6% Benzodiazepines 44% Cocaine Presence of psychiatric or somatic disorder is not mentioned.	Less axial diffusivity in Eight right hemisphere clusters 1) anterior corona radiata and inferior fronto-occipital fasciculus (IFOF) 2) forceps minor 3) anterior forceps minor Adjacent to parietal cortex: 4) close to the intraparietal sulcus 5) close to posterior thalamic radiation and IFOF Near SLF 6) and somatosensory cortex 7) and corticospinal tract Other areas 8) sagittal stratum, inferior longitudinal fasciculus (IFL) and IFOF	1) T=3.972 671 voxels 2) T=3.966 177 voxels 3) T=4.345 34 voxels 4) T=4.71 173 voxels 5) T=3.482 165 voxels 6) T=3.256 22 voxels 7) T=3.637 92 voxels 8) T=2.49 38 voxels
Liang et al. (2020)	180 60 (ketamine users) 64 (ketamine + polysubstance users) 56 (non-users)	Primarily Ketamine Users Mean age: 26.0 years Male/female 37/23 Ketamine Use 3.2 g/day 76 months Regular use: Cocaine 29.3% Metamphetamine 16.9% Marijuana 10.2% Hallicunogens 31.6% Presence of psychiatric or somatic disorder is not mentioned Ketamine + Polysubstance users Mean age 25.6 Male/female 36/28 Mean ketamine use: 3 g/day 77.7 months Regular use: Cocaine 69.2% Methamphetamine 29.7% Marijuana 27.7% Hallicunogens 27.7% Presence of psychiatric or somatic disorder was not mentioned.	Non-users Mean age 23.9 Male/female 24/32 No drug use is reported. Presence of psychiatric or somatic disorder was not mentioned.	1) Both primarily ketamine users and ketamine + polysubstance users had larger caudate nuclei than the non-drug controls. 2) Both ketamine groups had larger white matter volumes throughout the whole brain. 3) The K+polysubstance abuse showed even higher white matter volumes.	White matter volume was measured as a percentage of total intracranial volume. 1) (p = 0.030) 2) (p = 0.046) 3) (p = 0.011 compared to controls)	Earlier age of ketamine (both the primarily K and K+polysubstance users) use predicted larger white matter volumes.

FA, fractional anisotropy; IF, inferior longitudinal fasciculus; IFOF, inferior fronto-occipital fasciculus; SLF, superior longitudinal fasciculus.