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In particular, methamphetamine appears to cause hyperintensity and hypertrophy of white matter, marked shrinkage of hippocampi, and reduced gray matter in the cingulate cortex, limbic cortex, and paralimbic cortex in recreational methamphetamine users.Moreover, evidence suggests that adverse changes in the level of biomarkers of metabolic integrity and synthesis occur in recreational users, such as a reduction in N-acetylaspartate and creatine levels and elevated levels of choline and myoinositol.Chronic high-dose use can precipitate unpredictable and rapid mood swings, stimulant psychosis (e.g., paranoia, hallucinations, delirium, and delusions) and violent behavior.

Following presynaptic dopamine and glutamate co-release by such psychostimulants, ΔFos B functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.

Sufficiently overexpressing ΔJun D in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFos B).

Methamphetamine is known to possess a high addiction liability (i.e., a high likelihood that long-term or high dose use will lead to compulsive drug use) and high dependence liability (i.e.

a high likelihood that withdrawal symptoms will occur when methamphetamine use ceases).

As dry mouth is also a common side effect of other stimulants, which are not known to contribute severe tooth decay, many researchers suggest that methamphetamine associated tooth decay is more due to users' other choices.

They suggest the side effect has been exaggerated and stylized to create a stereotype of current users as a deterrence for new ones.

Sigma receptor activation by methamphetamine promotes methamphetamine-induced neurotoxicity by facilitating hyperthermia, increasing dopamine synthesis and release, influencing microglial activation, and modulating apoptotic signaling cascades and the formation of reactive oxygen species.

A moderate overdose of methamphetamine may induce symptoms such as: abnormal heart rhythm, confusion, difficult and/or painful urination, high or low blood pressure, high body temperature, over-active and/or over-responsive reflexes, muscle aches, severe agitation, rapid breathing, tremor, urinary hesitancy, and an inability to pass urine.

Muscle cramps such as "charley horse", sometimes severe and prolonged, can occur both in short-term use and more dangerously in long-term use due to electrolyte imbalance from poor diet and dehydration.

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