Methamphetamine has been identified as a potent full agonist

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.[142][143] 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).[142][144] 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.[142][145] 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.[149][150][151] TAAR1 activation by methamphetamine in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter.

In addition to its effect on the plasma membrane monoamine transporters, methamphetamine inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release.[152] This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters.[153] Other transporters that methamphetamine is known to inhibit are SLC22A3 and SLC22A5.[152] SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter

Methamphetamine is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B).[62][143][66] Sigma receptor activation by methamphetamine may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain.[62][66] Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger peripheral effects, a longer half-life, and longer perceived effects among heavy substance users.[155][156][157] At high doses, both enantiomers of methamphetamine can induce similar stereotypy and methamphetamine psychosis,[156] but levomethamphetamine has shorter psychodynamic effects.

Degradation

Degradation
A 2011 study into the destruction of methamphetamine using bleach showed that effectiveness is correlated with exposure time and concentration.[181] A year-long study (also from 2011) showed that methamphetamine in soils is a persistent pollutant.[182] In a 2013 study of bioreactors in wastewater, methamphetamine was found to be largely degraded within 30 days under exposure to light