Table 3.
Functional differences.
| References | N (ketamine vs controls) | Ketamine subjects (ketamine use-other substance use-comorbid disorders) | Controls | Significant differences ketamine subjects compared to controls | Statistic measure | Correlation |
|---|---|---|---|---|---|---|
| Liu et al. (2016) | 124–57 | 25% mood disorder, 15.3% anxiety disorder. “Many” ketamine users used other drugs like cannabis or cocaine. Mean ketamine use: not mentioned Male/female not mentioned Ketamine users performed worse than controls on intelligence and cognitive tasks Presence of psychiatric or somatic disorder was not mentioned. |
Healthy controls | -Less functional connectivity in orbital part of right inferior gyrus, left anterior cingulate and paracingulate gyri, right superior temporal gyrus and bilateral vermic lobule VI of cerebellum. -More functional connectivity left middle occipital gyrus. |
No test statistic reported | |
| Liao et al. (2016) | 130 (41–89) rsfMRI | Mean ketamine use: 2 g/day 3.4 years Mean age 26.8 years Male/female 33/7 Ketamine was consumed by snorting 100% Tobacco 75% Alcohol 70% Ecstasy 15% Diazepam 20% Marijuana 58% Methamphetamine 68% Amphetamine+caffeine No history of neurologic disorder or other psychiatric illnesses Excluded if other substance dependence (excl. nicotine) |
Drug-free controls Mean age 27.1 years Male female 70/18 50% Tobacco 55% Alcohol No personal history of neurologic or psychiatric illnesses |
Less thalamocortical connectivity between ketamine users and healthy controls. connectivity of thalamic nuclei with: prefrontal cortex 1) left medial dorsal nucleus motor/supplementary motor area 2) left ventral posterior lateral nucleus 3) right ventral lateral nucleus posterior parietal cortex 4) right pulvinar nucleus 5) left pulvinar n. 6) left medial dorsal n. 7) right ventral lateral n. 8) right lateral dorsal n. |
1) T=3.72, voxel 270 mm3 2) T=3.41 v=459 3) T=3.34 v=1354 4) T=3.72 v=243 5) T=2.76 v=108 6) T=4.32 v=108 7) T=3.20 v=162 8) T=3.53 v=405 |
Less thalamocortical connectivity in posterior parietal cortex and individual craving scores. (p < 0.05) A correlation between total ketamine intake and craving scores. (p = 0.003) |
| Liao et al. (2012) | 85 (41–44) rsfMRI | Mean ketamine use: 2 g/day 3.4 years Mean age 26.9 years Ketamine was consumed by snorting 0% Cocaine 2,4% Heroin 15% Diazepam 20% Marijuana 56% Methamphetamine 63% Amphetamine+caffeine No history of neurologic disorder or other psychiatric illnesses Excluded if other substance dependence (excl. nicotine) |
Drug-free controls Mean age 26.3 No history of neurologic or psychiatric illnesses |
1) Lower ReHo in right anterior cingulate cortex. 2) More ReHo in left precentral frontal gyrus. |
1) peak T=4.32 p < 0.001 voxel Z = 4.09 2) peak T=4.85 p < 0.001 Z = 4.54 |
Higher ReHo in left precentral gyrus negatively correlated with estimated total lifetime consumption (p = 0.035) and ketamine craving (p = 0.007). |
| Li et al. (2017) | 56 (36–20) rsfMRI |
Mean ketamine use: 4.9 years (M & F, dose not recorded) Mean age 25.2 (M) 27.5 (F) Male/female 26/10 Route of administration was not mentioned Mean tobacco use: 8.4 years (M) 12.1 years (F) Mean alcohol use: 4.3 years (M) 6.7 years (F) Subjects had no major medical or neurological illness |
Drug-free controls Mean age 25.3 (M) 25.1 (F) Male/female 11/9 Mean tobacco use: 2.5 years (M) 0 years (F) Mean alcohol use: 5.2 years (M) 1.9 years (F) Subjects had no major medical or neurological illness |
1) No difference in sgACC connectivity 2) Positive connectivity between sgACC and rostral ACC/medial prefrontal cortex/medial orbitofrontal cortex, bilateral temporal poles/superior temporal gyri, bilateral caudate head/ventral striatum/anterior thalamus and negative connectivity to bilateral occipital cortex, bilateral inferior frontal cortex/anterior insula (rIFC/AI), bilateral middle frontal gyrus and left angular gyrus |
1) A two sample t-test was performed 2) A one sample t-test was performed |
- sgACC-OFC connectivity negatively correlated with CES-D (p = 0.00001, r =-0.66) in KU (M & F) - sgACC-STG connectivity positively correlated with CES-D both in KU (p = 0.00002, r = 0.74) and in HC (p = 0.009, r = 0.74), men only - sgACC-dmPFC connectivity positively correlated with the CES-D in KU (p = 0.00003, r = 0.97), not in HC (p = 0.69, r = −0.16), female only |
| Morgan et al. (2014) | 26 (11–15) fMRI |
Mean ketamine use: 1.5 g/day 9.7 years Mean age 28 years Male/female 8/3 Route of administration was not mentioned 100% Tobacco 82% Alcohol 36% Cocaine 18% Ecstasy 73% Cannabis 1/11 personal history of mental illnesses somatic illness is not mentioned |
Polydrug controls Mean age 26.13 years Male/female 10/5 87% Tobacco 100% Alcohol 6.7% Cocaine 0% Ecstasy 27% Cannabis 1/15 personal history of mental illnesses somatic illness is not mentioned |
1) Less activity of right hippocampus and 2) Left parahippocampal gyrus in spatial memory task. 3) Less left caudate activation during memory updating. |
1) t=2.77 p = 0.03 controls>ketamine users 2) t=2.81 p = 0.03 3) t=2.6, p = 0.048 |
|
| Chan et al. (2012) | 6 (3–3) fMRI |
Mean ketamine use: 1–2 g/day 2 years Mean age not mentioned Male/female not mentioned Route of administration was not mentioned Presence of psychiatric or somatic disease not mentioned |
Drug-free controls Mean age not mentioned Male/female not mentioned Presence of psychiatric or somatic disease not mentioned |
Lower number of activated areas in cerebellum during simple motor activities. Consecutively, subject drank 200 ml of red wine and repeated the motor task. |
In controls, 55.7% of cerebellar volume was activated vs. 27.7% in ketamine users, and 21.1% in ketamine users + red wine condition. | |
| Liao et al. (2018) | 129 (40 ketamine smokers, 45 non-ketamine smokers, 44 non-ketamine –non-smokers. | Mean ketamine use: not mentioned Other substance; nicotine. Subjects were excluded if any other substance use disorder was present. |
-Nicotine smoking controls, -non ketamine, non-smoking |
more activation in anterior cingulate cortex in response to ketamine cues 1) left anterior cingulate cortex 2) precuneus 3) cingulate gyrus 4) left inferior parietal cortex 5) right posterior cingulate 6) left occipital cortex (lingual gyrus) 7) right parietal cortex (supramarginal gyrus) Smoking cues 8) right frontal cortex (precentral gyrus) Sexual cues 9) left cerebellum 10) middle temporal cortex Ketamine cues minus smoking cue 11) left inferior parietal cortex 12) posterior cingulate/precuneus 13) left middle temporal cortex lower activation in left cerebellum and middle temporal cortex in response to sexual cues |
1) peak T=4.45, voxel z = 4.28 Voxel size=378 mm3 2) peak T=4.19, voxel z = 4.05 Voxel size=361 mm3 3) peak T=3.96, voxel z=3.84 Voxel size = 77 mm3 4) peak T=3.76, voxel z = 3.66 Voxel size=53 mm3 5) peak T=3.76 voxel z = 3.66 Voxel size=45 mm3 6) peak T=3.63 voxel z = 3.53 Voxel size=56 mm3 7) peak T=3.62 voxel z = 3.52 Voxel size=53 mm3 8) peak T=4.20 voxel z = 4.06 Voxel size=33 mm3 9) peak T=4.65, voxel z = 4.46 Voxel size=123 mm3 10) peak T=4.33, voxel z = 4.17 Voxel size=80 mm3 11) peak T=4.22, voxel z = 4.14 Voxel size=130 mm3 12) peak T=3.74, voxel z = 3.68 Voxel size=81 mm3 13) peak T=3.58, voxel z = 3.53 Voxel size = 361 mm3 |
|
| Hung et al. (2020a) | 53 (34 ketamine users, 19 controls) | Ketamine users were divided between adolescent (onset before age 20) onset users and adult onset users (onset after age 20). Age: 25.33 years Mean ketamin use: not mentioned Male/female 26/8 Subjects testing positive on methamphetamine, Opioids, ecstasy and marijuana were excluded. Participants had no major medical or neurological illness. The level of education of ketamine users was significantly lower than in the control group. |
Participants had no major medical or neurological illness. Age: 25.26 years Male/female 11/8 |
Both 1) adolescent onset ketamine users and 2) adult onset ketamine users had higher functional connectivity between the left and right precuneus than 3) controls |
1) Z = 0.21 SD = 0.03 2) Z = 0.25 SD = 0.03 3) Z = −0.02 SD = 0.03 P <0.001 |
|
| Hung et al. (2020b) | 56 (36 ketamine users, 20 healthy controls | Age 25.2 years (M) 27.5 years (F) Male/female 26/10 Mean ketamine use: dose not recorded 59.4 months (M) 59.0 months (F) None of the ketamine users had a major medical, neurological illness. |
Age 25.3 years (M) 25.1 years (F) Male/female 11/9 |
Ketamine users showed higher connectivity between 1) caudate and the dorsal anterior cingulate cortex 2) pallidum and bilateral cerebellum |
1) voxel z=4.24 2) voxel z=5.28 |
The connectivity between putamen and lOFC correlated with months of ketamine use and BIS impulsivity scores (mediation analyes p = 0.00007–0.007) |
rsfMRI, resting-state functional magnetic resonance imaging; ReHo, regional homogeneity; KU, ketamine user; M, male; F, female; CES-D, Center of Epidemiological Study-Depression score; sgACC, subgenual anterior cingulate cortex; OFC, orbitofrontal cortex; STG, superior temporal gyrus; dmPFC, dorsomedial prefrontal cortex; fMRI, functional magnetic resonance imaging.