MDMA

MDMA acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine, which arises from its activity at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2).[4][51][52] MDMA is a monoamine transporter substrate (i.e., a substrate for DAT, NET, and SERT), so it enters monoamine neurons via these neuronal membrane transport proteins;[51] by acting as a monoamine transporter substrate, MDMA produces competitive reuptake inhibition at the neuronal membrane transporters (i.e., it competes with endogenous monoamines for reuptake).[51][53] MDMA inhibits both vesicular monoamine transporters (VMATs), the second of which (VMAT2) is highly expressed within monoamine neurons at vesicular membranes.[52] Once inside a monoamine neuron, MDMA acts as a VMAT2 inhibitor and a TAAR1 agonist.[51][52] Inhibition of VMAT2 by MDMA results in increased concentrations of the associated neurotransmitter (serotonin, norepinephrine, or dopamine) in the cytosol of a monoamine neuron.[52][54] Activation of TAAR1 by MDMA triggers protein kinase A and protein kinase C signaling events which then phosphorylates the associated monoamine transporters – DAT, NET, or SERT – of the neuron.[51] In turn, these phosphorylated monoamine transporters either reverse transport direction – i.e., move neurotransmitters from the cytosol to the synaptic cleft – or withdraw into the neuron, respectively producing neurotransmitter efflux and noncompetitive reuptake inhibition at the neuronal membrane transporters.[51]

Duloxetine, an SNRI

Duloxetine inhibits the reuptake of serotonin and norepinephrine (NE) in the central nervous system. Duloxetine increases dopamine (DA) specifically in the prefrontal cortex where there are few DA reuptake pumps via the inhibition of NE reuptake pumps (NET) thus allowing greater diffusion of DA in this brain region.[47] However, duloxetine has no significant affinity for dopaminergic, cholinergic, histaminergic, opioid, glutamate, and GABA reuptake transporters and can therefore be considered to be a selective reuptake inhibitor at the 5-HT and NE transporters. Duloxetine undergoes extensive metabolism, but the major circulating metabolites do not contribute significantly to the pharmacologic activity.[48][49]

DUH, how could I be so stupid?

No really, to my layman's ears they sound like they do the same basic thing: mess serotonin, dopamine, and norepinephrine to improve mood. If the story is more complicated than that, I don't see how a layman like me is going to gain any traction reading insanely complicated biochem nerdsauce like that.

Hence my appeal to r/drugs for help.