Chronic ketamine abuse causes diffuse brain damage visible on MRI. In 21 addicts with 0.5 to 12 years of use, lesions appeared in multiple brain regions after 2–4 years of addiction. Cortical atrophy was evident in the frontal, parietal, and occipital cortices. The pattern of injury differs from that caused by cocaine, heroin, or methamphetamine.
Long-term recreational ketamine use is associated with lower gray matter volume, reduced white matter integrity, and decreased functional connectivity between brain regions, particularly thalamocortical and corticocortical pathways. A systematic review of 16 studies involving 440 chronic users (average 2.4 grams per day for 2–9.7 years) compared with 259 drug-free controls and 44 poly-drug controls found these neuroanatomical differences. The observed brain changes may help explain cognitive and psychiatric side effects of prolonged ketamine abuse, including memory impairment and executive functioning problems. The findings suggest that efforts to curb ketamine abuse are warranted given its potential long-term effects on the brain.