ethanol

Probably the simplest and smallest molecule used as a psychoactive drug: It is neurotoxic, carcinogenic, and addictive, but of course still widely used as a "legacy drug". (see alcohol substitutes)

Being such a lightweight molecule, taken in relatively enormous doses (a typical alcoholic 'drink' might contain 15g of pure ethanol, approximately 1000x more than a typical dose of THC) it does a lot of stuff in the body. We can't easily characterize its psychoactive effects in terms of a single neurotransmitter, because it gets everywhere and affects pretty much every system.

It seems to act on most receptors generally as an "allosteric modulator", binding to a different site on the receptor than the usual (orthosteric) site of the endogenous ligand (e.g., it binds to GABA_A receptors at a different site than GABA itself would bind), but in a way that either up- or down-regulates the activity of the receptor with respect to its usual ligand.This seems unsurprising since it's such a small molecule; as a tiny "key" it's unlikely to activate any specific elaborate "lock", but it will accidentally have small effects on everything it touches For example, ethanol is a positive modulator of GABA_A receptor receptors, which may account for its general anxiolytic effect, but also a negative modulator of various glutamate receptors, which may account for its dyscoordinating "drunkenness" effect.

References:

• https://en.wikipedia.org/wiki/Alcohol_(drug)#Pharmacology