Brain damages in ketamine addicts as revealed by MRI (2013)

Although there have been relatively few, often methodologically diverse, studies to date of the mnemonic effects of ketamine, there is an emerging consensus that an acute dose of the drug impairs the manipulation of information in working memory and produces decrements in the encoding of information into episodic memory. Preliminary evidence suggests that ketamine may differ from other classic amnestic drugs in impairing aspects of semantic memory. Acute-on-chronic effects in ketamine users generally mimic the pattern seen in controlled studies with healthy volunteers. However, chronic ketamine use may be associated with a more specific pattern of memory decrements and with episodic memory impairment, which might not abate following cessation of use.

Key points

• Ketamine can be neurotoxic after neuraxial administration.
• The authors studied its mechanism by using lymphocyte and neuroblastoma cell lines in experimental conditions.
• Cell viability, apoptosis, and mitochondrial metabolic activity were studied.
• In smaller concentrations, ketamine induced apoptosis via mitochondrial pathway.
• In larger concentrations, ketamine caused necrotic cell death.

• Ketamine users displayed impaired verbal fluency (but not figural fluency).
• Ketamine users had impaired cognitive processing speed.
• Ketamine disrupted verbal learning, but not visual learning or verbal/nonverbal memory.
• Cumulative ketamine use correlated with worse memory and verbal learning.
• There was no correlation between abstinence duration and cognitive impairments.

Conclusion: Ketamine poly-drug users displayed predominantly verbal and visual memory impairments, which persisted in ex-users. The interactive effect of ketamine and poly-drug use on memory needs further investigation.

Results: Cognitive impairment was found only in current ketamine users in the domains of mental and motor speed (p < .001), visual and verbal memory (p < .001), and executive functions (p < .001). Depressive symptoms were also more frequently found in current ketamine users (p < .001).
Conclusion: Current ketamine use is associated with cognitive impairment. Illicit substance treatment and rehabilitation services should pay attention to ketamine's cognitive effects and motivate their clients to quit using ketamine and stay abstinent.

Prevention
In medical settings, NMDA receptor antagonists are used as anesthetics, so GABAA receptor positive allosteric modulators are used to effectively prevent any neurotoxicity caused by them.Drugs that work to suppress NAN include anticholinergics, benzodiazepines, barbiturates and agonists at the alpha-2 adrenergic receptor in the brain, such as clonidine.

When NMDA antagonists are administered in significantly lower doses than suggested above, they promote robust and rapid neurogeneration. It is this action which reverses the neuronal atrophy and loss of connectivity that characterizes psychiatric disorders such as depression and bipolar disorder.

FranX schreef:Goeie post trouwens... hadden jullie, ter aanvulling, deze al gezien:

Reduced Dorsal Prefrontal Gray Matter After Chronic Ketamine Use
http://www.stichtingopen.nl/en/psychedelics/publications/recent-publications/reduced-dorsal-prefrontal-gray-matter-after-chronic-ketamine-use

Duration of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex, whereas the estimated total lifetime ketamine consumption was negatively correlated with gray matter volume in left superior frontal gyrus.

Conclusion: We have demonstrated a reduction in frontal gray matter volume in patients after chronic ketamine use. The link between frontal gray matter attenuation and the duration of ketamine use and cumulative doses of ketamine perhaps suggests a dose-dependent effect of long-term use of the drug.

Einstein schreef:Op zich moeten cognitieve achteruitgang en hersenschade ook hand in hand gaan.

aan de andere kant vindt cognitieve achteruitgang altijd zijn oorzaak in het brein en is dus altijd een bepaalde vorm van hersenschade.

Einstein schreef:dat dit volgens mij niet over Olney's lesions gaat, maar over een andere vorm van hersenschade

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use—on brain structure in humans—remains poorly understood.

We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and the lateral prefrontal cortex and dissociative experiences.

These findings suggest that chronic ketamine use may be associated with widespread disruption of white matter integrity, and white matter pathways between subcortical and prefrontal cortical areas may in part predict individual differences in dissociative experiences due to ketamine use.

Olney's Lesions have not yet been proven or disproven to manifest in humans. No tests have been conducted to test the validity of post-dissociative development of vacuolization in human brain tissue, and critics claim that animal testing is not a reliable predictor of the effects of dissociative substances on humans:

dan hebben we het wel over langdurig misbruik va dissiociatieven

Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear.

This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 polydrug controls, matched for IQ, age and years in education. We used fMRI utilising an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus and the caudate nucleus during a virtual reality task of spatial memory.

Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.