Mescaline is a hallucinogenic phenethylamine first isolated from peyote cactus.

Mescaline Metabolites

Metabolites Found in Man

  • N-acetyl-mescaline [6]
  • N-acetyl-β-(3,4-dimethoxy-5-hydroxyphenyl) ethylamine [6]
  • 3,4-dihydroxy-5-methoxyphenylacetic acid [3]
  • 3,4,5-trimethoxyphenylacetic acid [3][6]
  • 3,4-dimethoxy-5-hydroxyphenyethylamine [3]

The metabolite 3,4,5-trimethoxyphenylacetic acid is formed in vivo from the intermediate aldehyde metabolite 3,4,5-Trimethoxyphenylacetaldehyde created by the action of SSAO on mescaline (according to several animal studies).

Mescaline, 3,4,5-trimethoxyphenylacetic acid, N-acetyl-β-(3,4-dimethoxy-5-hydroxyphenyl) ethylamine and N-acetyl-mescaline have been identified in human urine after mescaline administration in the following amounts: mescaline 55–60%, 3,4,5-trimethoxyphenylacetic acid 27–30%, N-acetyl-β-(3,4,dimethoxy-5-hydroxyphenyl) ethylamine 5% and N-acetylmescaline less than 0.1%.[6]

Metabolites Found in Rats

  • 3,4,5-trimethoxyphenylethanol [3]

Metabolites Found in Rabbits

  • 2-hydroxy-1,3-dimethoxyderivative [3]
  • 3-hydroxy-1,2-dimethoxyderivative [3]

Mescaline Metabolism

Aldehyde Dehydrogenase

Aldehyde dehydrogenase appears to play a role suppressing the effects of mescaline.

Anecdotal reports indicate that Aldehyde dehydrogenase inhibitors boost the effects of mescaline in man. There is evidence that supports these claims. Rats trained in a 2 lever operant chamber to discriminate between the drugged state of mescaline and the nondrugged state where given aldehyde dehydrogenase inhibitors. Test results indicated that aldehyde dehydrogenase inhibitors enhanced the effects of mescaline in rats.[1]


Anecdotal reports indicate that the weak SSAO inhibitor caffeine boosts the effects of mescaline in man. There is evidence that supports these claims. In vitro tests using rabbit lung tissue showed mescaline metabolism was sensitive to inhibition by the potent SSAO inhibitor semicarbazide.[2]

It was also found that in vitro rabbit liver enzyme preparations deaminated mescaline to 3,4,5-trimethoxyphenylacetic acid. This reaction was inhibited by the SSAO inhibitors iproniazid and semicarbazide (Daly et al., 1962).

There is evidence that suggests that mescaline is degraded by SSAO in particulate preparations from hog kidney and liver, and mouse liver.[4]

Chemical Properties

PubChem Compound ID: 4076
Molecular Weight: 211.25758 [g/mol]
Molecular Formula: C11H17NO3
XLogP3: 0.7
IUPAC Name: 2-(3,4,5-trimethoxyphenyl)ethanamine
InChI: InChI=1S/C11H17NO3/c1-13-9-6-8(4-5-12)7-10(14-2)11(9)15-3/h6-7H,4-5,

Theoretical Active Metabolites


For decades scientists have argued that mescaline is not lipid soluble enough to elicit psychedelic activity. Its XLogP3 of 0.7 should prevent entry into the brain. For this reason it has been suggested that a metabolite of mescaline is psychedelic and not mescaline itself. However an active metabolite of mescaline had not yet been identified.

One theory states that mescaline's metabolite 3,4,5-trimethoxyphenylacetaldehyde condenses with dimethylamine, piperidine, or pyrrolidine in vivo in humans to form one of three possible theoretical active metabolites of mescaline: N,N-dimethyl-2-(3,4,5-trimethoxyphenyl)acetamide, 1-piperidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone, or 1-pyrrolidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone.

These theoretical alkaloid metabolite of mescaline possibly degrade rapidly, producing effects for only a short period of time, but are continuously being created as metabolites of mescaline throughout the duration of the effects of mescaline.

The theoretical piperidine alkaloid metabolite of mescaline 1-piperidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone has an XLogP3-AA of 2.1. This compound can easily cross the blood brain barrier, while mescaline with an XLogP3 of 0.7 clearly cannot. It's theorized that 1-piperidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone is a primary substrate of SSAO and that mescaline itself acts as a competitive SSAO inhibitor, allowing 1-piperidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone to produce effects. Without mescaline being present as a competitive inhibitor of SSAO, 1-piperidin-1-yl-2-(3,4,5-trimethoxyphenyl)ethanone is theorized to be rapidly destroyed by SSAO rendering it inactive. Thus a complex interaction exists between mescaline, it's aldehyde metabolite, and it's alkaloid metabolites.

Tests performed on rats indicate that aldehyde dehydrogenase inhibitors enhance the effects of mescaline.[1] Anecdotal human reports also indicate that this happens in man. These inhibitors would prevent highly reactive aldehyde metabolites of mescaline from being converted to acids. This would give them more time to condense with dimethylamine, piperidine, or pyrrolidine in vivo in humans, thereby possibly forming more alkaloid metabolites of these amines. This helps support the theory that active alkaloid metabolites are being created in vivo from mescaline's intermediate aldehyde metabolite 3,4,5-Trimethoxyphenylacetaldehyde, and that they are responsible for the psychedelic effects attributed to mescaline and not mescaline itself.

Aldehyde dehydrogenase inhibitors cannot act on the alkaloid mescaline, they only degrade aldehydes and similar compounds. Curiously the same test on rats showed that the aldehyde metabolite of mescaline 3,4,5-trimethoxyphenylacetaldehyde did not show mescaline activity in rats treated with aldehyde dehydrogenase inhibitors. The results indicate that 3,4,5-trimethoxyphenylacetaldehyde is not capable of producing the effects of mescaline on its own.

3,4-dimethoxy-2-phenylethylamine, a very close relative of mescaline, was found to be converted to is acid form (after conversion to it's aldehyde form) by the action of aldehyde dehydrogenase, xanthine oxidase, and aldehyde oxidase. [5]

Therefor, simply inhibiting aldehyde dehydrogenase may not be enough to illicit mescalines effects from 3,4,5-trimethoxyphenylacetaldehyde when mescaline and other metabolites are not present. 3,4,5-trimethoxyphenylacetaldehyde might be attacked by enzymes other than aldehyde dehydrogenase when its not produced in vivo form mescaline, leading to inactivity. There are many other enzymes capable of metabolizing aldehydes (i.e., xanthine oxidase, aldose reductase, aldehyde oxidase, etc.). Mescaline or one of its metabolites may be acting as enzyme inhibitors protecting 3,4,5-trimethoxyphenylacetaldehyde from other enzymes until it reaches a point where it can condense with dimethylamine, piperidine, or pyrrolidine to form one of three possible theoretical active metabolites of mescaline.

1. Browne RG, Ho BT.
Discriminative stimulus properties of mescaline: mescaline or metabolite? Pharmacol Biochem Behav. 1975 Jan-Feb;3(1):109-14. PubChem PMID: 1129346
2. Roth RA Jr, Roth JA, Gillis CN.
J Pharmacol Exp Ther. 1977 Feb;200(2):394-401. Disposition of 14C-mescaline by rabbit lung. PubMed PMID: 839444
3. Peter Kovacic1, and Ratnasamy Somanathan;
Novel, unifying mechanism for mescaline in the central nervous system; Oxidative Medicine and Cellular Longevity 2:4, 181-190; September/October 2009 (Download Attached PDF Document)
4. E. Albert Zeller, James Barsky, Elaine R. Berman, Marshall S. Cherkas and James R. Fouts;
DEGRADATION OF MESCALINE BY AMINE OXIDASES; Department of Biochemistry, Northwestern University, Medical School, Chicago, Illinois; J Pharmacol Exp Ther. 1958 Dec;124(4):282-9; PubMed PMID: 13611629
5. Georgios I Panoutsopoulos;
Contribution of aldehyde oxidizing enzymes on the metabolism of 3,4-dimethoxy-2-phenylethylamine to 3,4-dimethoxyphenylacetic acid by guinea pig liver slices.; Department of Experimental Pharmacology, Medical School, Athens University, Greece; Cellular Physiology and Biochemistry (impact factor: 2.86). 02/2006; 17(1-2):47-56. DOI:10.1159/000091463; PubMed PMID: 16543721
6. K. D. Charalampous, K. E. Walker, John Kinross-Wright;
Metabolic fate of mescaline in man; Psychopharmacologia, Volume 9, Issue 1 , pp 48-63; 1966-01-01; ISSN 0033-3158; DOI 10.1007/BF00427703
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