One of mescaline’s metabolites is known as 3,4,5-trimethoxyphenylacetaldehyde. If the aldehyde enzyme system is compromised, 3,4,5-trimethoxyphenylacetaldehyde can combine with dimethylamine to form an alkaloid known as N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine. This alkaloid is nearly identical to the dimethylamine alkaloid metabolite of elemicin known as 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one. The only difference is that the elemicin metabolite has oxygen on the 1 position of the tail and the mescaline metabolite doesn’t.
N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine has an XLogP3 2.1. This is high enough to produce psychedelic effects. Mescaline itself cannot. This is because of it’s very low XLogP3. So this is very possibly the active metabolite of mescaline. It’s probably very potent, active at a few mg. But in order to form, the aldehyde enzymes need to be inhibited.
I am willing to bet that mescaline inhibits the aldehyde enzymes (such as xanthine oxidase) just enough to allow this other alkaloid to form.
The dimethylamine form of elemicin known as 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one has an XLogP of 1.5. This is not that great. This is why taking filtered black pepper tea helps improve the effects of elemicin. It causes the piperidine form to be created instead. 3-piperidin-1-yl-1-(3,4,5-trimethoxyphenyl)propan-1-one has an XLogP3 of 2.3. This forms when you supplement with piperidine (from black pepper tea).
It’s very likely that if this theory is correct then supplementing with filtered black pepper tea will greatly potentiate the effects of mescaline, because instead of mescaline forming N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine as its potential active metabolite, it would form the piperidine metabolite which has an XLogP3 of 3.34.
Note that caffeine very noticeably boosts the effects of all allylbenzenes in a way identical to how it works for mescaline (this is judging by the impact it has on the experience according to SWIM).
Note also that caffeine is a xanthine oxidase inhibitor. This might help N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine form from 3,4,5-trimethoxyphenylacetaldehyde. It’s very likely that 3,4,5-trimethoxyphenylacetaldehyde is attacked by xanthine oxidase because its an aldehyde. Xanthine oxidase attacks a lot of aldehydes, and could prevent N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine from forming. So if this is the active metabolite of mescaline, then it makes sense that drinking coffee would potentiate mescaline, and it does.
Also interesting to note is that the phenethylamine form of methyl eugenol, known as 3,4-Dimethoxyphenethylamine occurs with mescaline in many mescaline containing cacti. This, although inactive as a psychedelic, is a very potent aldehyde oxidase inhibitor. Mescaline is 3,4,5- Trimethoxyphenethylamine. It’s just got one more methoxy group, that’s it. I’ll bet mescaline potently inhibits either aldehyde oxidase or xanthine oxidase. That’s why mescaline works. Mescaline probably inhibits the aldehyde enzymes, allowing it’s aldehyde metabolite to form a more potent psychedelic that passes the BBB. Mescaline itself cannot pass the BBB. It’s too water soluble. So only a metabolite can be active.
The dimethylamine metabolites of elemicin and mescaline are shown below. Notice how similar they are.
On the left is the elemicin metabolite 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)propan-1-one.
On the right is the mescaline metabolite N,N-dimethyl-3-(3,4,5-trimethoxyphenyl)propan-1-amine.
