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Someone please explain to me the pharmacology of mescaline

MagickalKat777

MagickalKat777

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It must be extremely complex... Euphoria that puts MDMA to shame that doesn't seem to rely on a massive serotonin release, visuals that rival LSD and DMT in intensity, very easy on the body (I imagine no effect on 5HT2c since I get no anxiety whatsoever on it whereas shrooms fucking kill me)... It literally is all of the good things about other drugs rolled into one amazing drug and other than the duration it really has NO negatives... After having it, it honestly seems like all of the other chemicals are trying to live up to mescaline but failing miserably...
 
Also of interest is something that I noticed yesterday but just read straight from Shulgin's own report... When it hits, BP and pulse drop below baseline... that has to be entirely unique in the psychedelic world. I went to the doctor and my BP was only 95/80... about 20 points lower than normal...
 
Nobody? I've searched and can not find receptor affinities/bindings or anything for it unlike MDXX, cannabis, benzos, LSD, etc. I did find an article saying that it was an MAOI but I seriously question that since we combo'd it with MDMA and didn't experience any nasty negatives.
 
from wiki:
Mescaline acts similarly to other psychedelic agents. It binds to and activates the serotonin 5-HT2A receptor with a high affinity as a partial agonist. How activating the 5-HT2A receptor leads to psychedelia is still unknown, but it likely somehow involves excitation of neurons in the prefrontal cortex.
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Pharmacokinetics

Tolerance builds with repeated usage, lasting for a few days. Mescaline causes cross-tolerance with LSD and other psychedelics.

About half the initial dosage is excreted after 6 hours, but some studies suggest that it is not metabolized at all before excretion.

Mescaline appears to not be subject to metabolism by CYP2D6 and between 20 and 50% of mescaline is excreted in the urine unchanged, and the rest being excreted as the carboxylic acid form of mescaline, a likely result of MAO degradation.

The LD50 of mescaline has been measured in various animals: 212 mg/kg i.p. (mice), 132 mg/kg i.p. (rats), and 328 mg/kg i.p. (guinea pigs).
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mescaline will work similar to the 2C series, if i aint been wrong.
you liked mescaline better..that doesnt mean mescaline works nothing like other phen psychedelics.
 
My knowledge in pharmacology is currently self-taught so if someone knows more feel free to correct me. Below is mescaline's normalized affinity for various sites, "higher affinities have higher pKi values".

Psychedelics and the Human Receptorome (1) said:
Mescaline: 4.00 Alpha2C, 3.97 5ht2b, 3.61 5ht1a, 3.44 Imidazoline1, 3.16 5ht1e, 2.92 Alpha2A; 0.00: 5ht2a, 5ht2c, 5ht6, 5ht1d, D1, D2, D3, D4, D5, Alpha1A, Alpha1B, 5ht5a, Alpha2B, 5ht7, Beta1, Beta2, SERT, DAT, NET, 5ht1b, Sigma1, Sigma2, DOR, KOR, MOR, M1, M2, M3, M4, M5, H1, H2, CB2, CB1, Ca+Channel, NMDA
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From the other studies I found mescaline has higher efficacy(2) and affinity(3) at 5-HT2C over 5-HT2A. Mescaline is not the optimal molecule for 5-HT2A docking, this substitution pattern has been implied through Shulgin (and proven by others) that it's not as effective as the classic 2,4,5. Maybe the other listed sites could help explain why you prefer it over other compounds. On top of everything from my understanding of functional selectivity it's not always "where" you act rather "how you act", shown with 5-HT2A signalling different with serotonin neurotransmitter and psychedelics.

(1) Psychedelics and the Human Receptorome (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814854/)

(2) Functional Selectivity of Hallucinogenic Phenethylamineand Phenylisopropylamine Derivatives at Human5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors (http://jpet.aspetjournals.org/content/321/3/1054.full.pdf)

(3) Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives (http://pubs.acs.org/doi/abs/10.1021/jm970219x)
 
The 5-ht1 receptors, to my understanding, produce a mood elevation. 5-ht1a promotes oxytocin release and therefore empathy.

That mescaline has 5-ht1 affinity is quite surprising, as I had been under the impression that phenethylamines in general have no affinity for the 5-ht1 receptors, whereas most tryptamines have significant 5-ht1 affinity.

EDIT: Apparently MDMA, too, has 5-ht1a affinity.
 
so it sounds like not much is known about the pharmacology of this amazing substance.

5HT2C is what causes the nausea, no? It seems to not have that effect in me but all of my friends have barfed their guts out...

It also sounds like mescaline is like amanita in that you could potentially drink your own urine and continue to trip - is the carboxylic acid active? Just curious, not going to drink my piss lol.
 
Also I gave some to a friend of mine who is an opiate addict and she is now going through intense opiate withdrawal... What would mediate that? I really hope it goes away when the peak comes and helps her work through her opiate withdrawal... she's barfed 2 times now... projectile style...
 
kat no idea about the opiate withdrawal thing, but, i dont see how mescaline could induce opiate withdrawal..it shouldnt have any effect on opiate receptors.
maybe the nausea is just from the effects of the drug? I know in fear and loathing in las vegas mescaline made Dr. Gonzo throw up, its very possible its just from the actual mescaline.
Are you using cactus extract? apparently lots of people puke from that..
i looked real quick and i think its 5HT1a that causes nausea?
wiki says
It binds to and activates the serotonin 5-HT2A receptor with a high affinity as a partial agonist.[12] How activating the 5-HT2A receptor leads to psychedelia is still unknown, but it likely somehow involves excitation of neurons in the prefrontal cortex.
i am pretty sure all phenethylamine psychedelics are releasing agents, and thats how they work (which would explain why MAOIs when mixed with phens would cause serotonin syndrome) and that the binding profiles of each droog are just slightly different.
Have you tried 2CB? i am pretty sure some people say thats a lot like mescaline..
 
MagickalKat777 said:
so it sounds like not much is known about the pharmacology of this amazing substance.
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Did you overlook my post with fairly extensive information on it's pharmacology? When you say "not much" I'd liken that to these newer research chemicals not mescaline, one of the longest known psychedelics to the scientific community. What is missing from the pharmacological data you're interested in? I'll see if I can't find it.

As for the vomiting I've always been under the impression synthetic or natural extract both would cause vomiting or nausea. I think Huxley is where I got this idea from so I can't speak without some uncertainty.

Edit: 5-HT3 makes more sense for nausea/vomiting, but I don't know it's binding data at this site.
 
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That's the thing... this one seems to have a weird pharmacological profile... its not made me vomit but everyone else who took it sure did... and my friend seriously is going through massive opiate withdrawal right now... and she's miserable. Its her birthday and she's homeless and I just wanted her to have a good time - she did with the MDMA but the mescaline threw her into the bathroom immediately and then threw her into opiate withdrawal...

And somehow I did overlook your post... jesus mescaline must have the most complicated pharmacology of any substance out there... that's a LOT of different receptors!

EDIT: LSDMDMA&AMP - 2C-B is nothing like mescaline. 2C-T-2 is the closest but still doesn't come close to it...
 
Astavats said:
My knowledge in pharmacology is currently self-taught so if someone knows more feel free to correct me. Below is mescaline's normalized affinity for various sites, "higher affinities have higher pKi values".
Originally Posted by Psychedelics and the Human Receptorome (1)
Mescaline: 4.00 Alpha2C, 3.97 5ht2b, 3.61 5ht1a, 3.44 Imidazoline1, 3.16 5ht1e, 2.92 Alpha2A; 0.00: 5ht2a, 5ht2c, 5ht6, 5ht1d, D1, D2, D3, D4, D5, Alpha1A, Alpha1B, 5ht5a, Alpha2B, 5ht7, Beta1, Beta2, SERT, DAT, NET, 5ht1b, Sigma1, Sigma2, DOR, KOR, MOR, M1, M2, M3, M4, M5, H1, H2, CB2, CB1, Ca+Channel, NMDA
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(1) Psychedelics and the Human Receptorome (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814854/)
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The article where these values are taken from should be considered with some scepticism! As Astatvats correctly cited, these are so-called "normalized" affinities and already the way how the author, Thomas S. Ray, established this "normalization" is dubious. Despite the huge information presented in that article, I wouldn't put too much trust into it.
Furthermore (rhetorical, but anyway) never forget: Affinity does not equal activity.

Nausea, sometimes to the extend of vomiting, is not unusual with both peyote and mescaline. In any case, I wouldn't call mescaline "easy on the body" at doses where OEVs are experienced. Of course, YMMV, but comparing mescaline to other psychedelics, this usually ain't the most benign one with respect to physical side-effects.


Peace! - Murphy
 
This is odd to me because mescaline had NO physical side effects in me... I did get nausea when I took 772mg but I didn't have any other negative bodyload. And the peripheral anti-stimulation effect is rather interesting...

This is no extract though. Its synthetic HCl. May have something to do with it.
 
The affinity data for 5-HT2A and C given in that article may be somewhat misleading, as the PDSP measurements use antagonist radioligands for these receptors. The Ki's for mescaline given in Bradens thesis are 4142 (5-HT1A, [3H]8-OH-DPAT), 1499 (h5-HT2A, [125I]DOI), 2438 (h5-HT2C, [125I]DOI) and 14,640 (h5-HT2A, [3H]ketanserin).
 
MagickalKat777 said:
wow that is total gibberish to me...

Btw its apparently an MAOI as well - explains why it makes a roll last so damn long.
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Mescaline is best though of as a substrate for MAO, rather than an inhibitor.

the affinities and pharmacological effects of mescaline are nothing special. as a hallucinogen it is equally good at activating both PLC-IP and the PLA2-AA pathways downstream of 5ht2a about 60% efficacy. probably gibberish to you

it is a beta blocker which explains the effect on BP and heart rate.

pure mescaline causes people to throw up just as much as the extracts. The good thing to be said is that it gets the hangover done first rather than afterwards.

>700mg of pure hydrochloride is a rather excessive dose, this is equivalent to almost a gram of sulphate...
 
MAOI definately makes sense with MESCALINE.

From experiments (unlike the more popular 2c-B, which was once sold as a sexual aid at low dose levels) there definately seems to be a minimum effective dose, of which after that it's fairly steep dose response (I.e 100-200mg might just be baseline but 300-400mg is suddenly full psycadelic - there is no middle ground)

never got round to trying it but would be willing to bet good money that ONDANSETRON (5ht3 antagonist) would help with MOST psycadelic nausea. It is used in chemotherapy for drugs which don't directly bind to 5ht3, wondering whether even if such compounds attribute their main actions from other receptors whether in the stomach they still HIT the 5ht3 rather hard.
 
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