Interactions
Methamphetamine is metabolized by the liver enzyme CYP2D6, so CYP2D6 inhibitors will prolong the elimination half-life of methamphetamine. Methamphetamine also interacts with monoamine oxidase inhibitors (MAOIs), since both MAOIs and methamphetamine increase plasma catecholamines; therefore, concurrent use of both is dangerous. Methamphetamine may decrease the effects of sedatives and depressants and increase the effects of antidepressants and other stimulants as well. Methamphetamine may counteract the effects of antihypertensives and antipsychotics owing to its effects on the cardiovascular system and cognition respectively. The pH of gastrointestinal content and urine affects the absorption and excretion of methamphetamine. Specifically, acidic substances will reduce the absorption of methamphetamine and increase urinary excretion, while alkaline substances do the opposite. Owing to the effect pH has on absorption, proton pump inhibitors, which reduce gastric acid, are known to interact with methamphetamine. Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans. Similarly, norepinephrine–dopamine reuptake inhibitors (NRIs) like methylphenidate and bupropion prevent norepinephrine and dopamine release induced by amphetamines and bupropion has been found to reduce the subjective and sympathomimetic effects of methamphetamine in humans
Pharmacodynamics
Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems. Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). When methamphetamine binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters. Methamphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux. TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels. TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter
Detection in biological fluids
Methamphetamine and amphetamine are often measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics. Chiral techniques may be employed to help distinguish the source of the drug to determine whether it was obtained illicitly or legally via prescription or prodrug. Chiral separation is needed to assess the possible contribution of levomethamphetamine, which is an active ingredients in some OTC nasal decongestants, toward a positive test result. Dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine


