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In human studies, long-term recreational ketamine use has been associated with structural brain changes, including reduced prefrontal gray matter volume and impaired white matter connectivity, which are potentially linked to chronic low-grade inflammation ( 5.2.2 Mitochondrial dysfunction Ketamine disrupts mitochondrial function by reducing the membrane potential, increasing cytochrome c release, and promoting ROS generation, which collectively induce neuronal apoptosis ( Human studies have identified metabolic abnormalities in ketamine abusers, particularly in the prefrontal cortex, which may reflect mitochondrial dysfunction ( 5.2.3 Dose and frequency dependence The neurotoxic effects of ketamine are highly dependent on its dosage and frequency of use

Furthermore, studies in vitro have shown that it inhibits the activity of the metalloproteinases MMP-1 and MMP-2, enzymes involved in the breakdown of the dermal matrix

Your glial cells can be involved in maladaptive mechanisms and play a role in pain generation, says Dickenson