Methamphetamine

Concurrent use of any monoamine oxidase inhibitor — irreversible (phenelzine, tranylcypromine), reversible (moclobemide), or selective (selegiline, rasagiline) — with methamphetamine is absolutely contraindicated. Fatalities are documented.

Severe cardiovascular disease, uncontrolled hypertension, or structural heart disease. Methamphetamine's sympathomimetic effects impose acute hemodynamic stress that exceeds the compensatory capacity of a compromised cardiovascular system.

History of cardiac arrhythmia, prolonged QT interval, or cardiomyopathy. Risk of fatal arrhythmia is elevated but not absolute if cardiovascular status is monitored.

History of arrhythmia or cardiomyopathy is a relative contraindication. Methamphetamine's noradrenergic effects exacerbate cardiac conduction abnormalities and may precipitate fatal arrhythmias in susceptible individuals.

History of epilepsy or other seizure disorder. Methamphetamine lowers seizure threshold, increasing breakthrough seizure risk even in patients on anticonvulsant therapy.

History of seizures or epilepsy is a relative contraindication. Methamphetamine lowers seizure threshold, and seizures are a recognized component of acute methamphetamine toxicity.

History of methamphetamine-induced psychosis, schizophrenia, schizoaffective disorder, or other primary psychotic disorder. Sensitization mechanisms ensure high probability of psychotic relapse upon re-exposure.

Concurrent use of SSRIs, SNRIs, tramadol, or other serotonergic medications. Additionally, CYP2D6 inhibition by some SSRIs (fluoxetine, paroxetine) increases methamphetamine plasma concentrations.

Bipolar disorder is a relative contraindication. Stimulant exposure may precipitate manic or mixed episodes. The combination of direct catecholaminergic stimulation and prolonged sleep deprivation creates dual mania triggers.

Uncontrolled or inadequately treated hyperthyroidism. The synergistic catecholaminergic amplification creates disproportionate cardiovascular risk.

Pregnancy at any stage. Prenatal exposure documented to cause adverse neonatal outcomes in human cohorts.

Narrow-angle glaucoma or untreated open-angle glaucoma. Methamphetamine's mydriatic effect can precipitate acute intraocular pressure elevation.

Concurrent use of any monoamine oxidase inhibitor — irreversible (phenelzine, tranylcypromine, isocarboxazid), reversible (moclobemide), or dietary (Syrian rue/harmine/harmaline) — with methamphetamine is absolutely contraindicated. Documented fatalities. This is among the most dangerous drug combinations in pharmacology.