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An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, substantially reduced or no urine output, cardiogenic shock, bleeding in the brain, circulatory collapse, hyperpyrexia (i.e., dangerously high body temperature), pulmonary hypertension, kidney failure, rapid muscle breakdown, serotonin syndrome, and a form of stereotypy ("tweaking").This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine.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.The FDA also advises individuals with bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome to monitor their symptoms while taking methamphetamine.The physical effects of methamphetamine can include loss of appetite; hyperactivity; dilated pupils ( Mydriasis ); excessive sweating; increased movement; dry mouth and teeth grinding (leading to "meth mouth"); headache; irregular heartbeat (usually as accelerated heartbeat or slowed heartbeat); rapid breathing; high blood pressure or low blood pressure; high body temperature; diarrhea or constipation; blurred vision; dizziness; twitching; muscle cramps, spasms, pain or stiffness; numbness; tremors; dry skin; acne; and pale appearance or flushed skin.

The NF-κB-mediated neuroimmune response to methamphetamine use which results in the increased permeability of the blood–brain barrier arises through its binding at and activation of sigma receptors, the increased production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and damage-associated molecular pattern molecules (DAMPs), the dysregulation of glutamate transporters (specifically, EAAT1 and EAAT2) and glucose metabolism, and excessive Ca Moreover, methamphetamine neurotoxicity is associated with an increased risk of Parkinson's disease, an effect which partially arises through excessive cytosolic and synaptic production of reactive oxygen species and autoxidation of dopamine.Dextromethamphetamine is a much stronger CNS stimulant than levomethamphetamine.Both methamphetamine and dextromethamphetamine are illicitly trafficked and sold owing to their potential for recreational use.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.

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