Isomescaline · 2,3,4-Trimethoxyphenethylamine
#91 IM SYNTHESIS: A solution of 8.0 g 2,3,4-trimethoxybenzaldehyde in 125 mL nitromethane containing 1.4 g anhydrous ammonium acetate was held at reflux for 1.5 h. The conversion of the aldehyde to the nitrostyrene was optimum at this time, with a minimum development of a slow-moving spot as seen by thin layer chromatography on silica gel plates using CHCl3 as a developing solvent; the Rf of the aldehyde was 0.31 and the Rf of the nitrostyrene was 0.61. The excess nitromethane was removed under vacuum, and the residue was dissolved in 20 mL hot MeOH. On cooling, the yellow crystals that formed were removed by filtration, washed with cold MeOH and air dried yielding 4.7 g yellow crystals of 2,3,4-trimethoxy-β-nitrostyrene, with a mp of 73–74 °C. From the mother liquors, a second crop of 1.2 g was obtained.
A solution of 4.0 g LAH in 80 mL THF under He was cooled to 0 °C and vigorously stirred. There was added, dropwise, 2.7 mL of 100% H2SO4, followed by a solution of 4.7 g 2,3,4-trimethoxy-β-nitrostyrene in 40 mL anhydrous THF. The mixture was stirred at 0 °C for 1 h, at room temperature for 1 h, and then brought briefly to a reflux on the steam bath. After cooling again, the excess hydride was destroyed with 4.7 mL H2O in THF, followed by the addition of 18.8 mL 15% NaOH which was sufficient to convert the solids to a white and granular form. These were removed by filtration, the filter cake washed with THF, the mother liquor and filtrates combined, and the solvent removed under vacuum. The residue was added to dilute H2SO4, and washed with 2×75 mL CH2Cl2. The aqueous phase was made basic with 25% NaOH, and extracted with 2×50 mL CH2Cl2. The solvent was removed from these pooled extracts and the amber-colored residue distilled at 95–100 °C at 0.3 mm/Hg to provide 2.8 g of 2,3,4-trimethoxyphenethylamine as a white oil. This was dissolved in 20 mL IPA, neutralized with about 1 mL concentrated HCl, and diluted with 60 mL anhydrous Et2O. After filtering, Et2O-washing, and air drying, there was obtained 3.2 g of 2,3,4-trimethoxyphenethylamine hydrochloride (IM) as a white crystalline product.
DOSAGE: greater than 400 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 300 mg) “No effects whatsoever.”
(with 400 mg) “Maybe a slight tingle at the hour-and-a-half point. Maybe not. Certainly nothing an hour later. Put this down as being without action.”
EXTENSIONS AND COMMENTARY: Some fifty years ago this material was given the name “reciprocal mescaline” in that it was believed to exacerbate the clinical symptoms in schizophrenic patients. In the original report, one finds: “Thus we have discovered an extremely remarkable dependency of the intoxicating action upon the position of the three methoxy groups. , the 3,4,5-trimethoxy-β-phenethylamine, produces in the normal subject a much stronger over-all intoxication than in the schizophrenic patient, whereas 2,3,4-trimethoxy-β-phenethylamine has quite the opposite effect. It has little action in healthy individuals, being almost without intoxicating properties, but it is very potent in the schizophrenic. The metabolic conversion products of the “reciprocal” will be further studied as soon as the study of the metabolism of the proper is complete.”
This is a pretty rich offering, and one that the present medical community has no qualms about discarding. At the bookkeeping level, the promised further studies have never appeared, so all may be forgotten as far as potential new discoveries might be concerned.
One recent related study has been reported, tying together isomescaline and schizophrenia. Through the use of radioactive labelling, the extent of demethylation (the metabolic removal of the methyl groups from the methoxyls) was determined in both schizophrenic patients and normal subjects. When there was a loading of the person with methionine (an amino acid that is the principal source of the body’s methyl groups), the schizophrenics appeared to show a lesser amount of demethylation.
But might either of these two observations lead to a diagnostic test for schizophrenia? At the present time, the conventional thinking is that this probably cannot be. The illness has such social and genetic contributions, that no simple measure of a response to an almost-psychedelic, or minor shift of some urinary metabolite pattern could possibly be believed. No independent confirmation of these properties has been reported. But maybe these findings are valid. A major problem in following these leads does not involve any complex research protocols. What must be addressed are the present regulatory restrictions and the Federal law structure. And these are formidable obstacles.
13 May 2016 · Creative Commons BY-NC-SA ·

About PiHKAL · info

This version of Book II of PiHKAL is based on the Erowid online version, originally transcribed by Simson Garfinkle and converted into HTML by Lamont Granquist. I drew also on “Tyrone Slothrop’s” (Unfinished) Review of PIHKAL to enumerate the many analogues mentioned in PiHKAL but not described at length. Many, many others have since been added.
I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice. Typically the change is little more than expanding a prefix or setting it in italics. The history page has further details.

Cautionary note

“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.
“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
Alexander T. Shulgin

Copyright notice

The copyright for Book I of PiHKAL has been reserved in all forms and it may not be distributed. Book II of PiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.

Ordering information

PiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of phenethylamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Though Sasha and Ann have put Book II of PiHKAL in the public domain, available to anyone, I strongly encourage you to buy a copy. We owe them — and there’s still nothing quite like holding a real book in your hands.
PiHKAL (ISBN 0-9630096-0-5) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.
Transform Press,
Box 13675
Berkeley, CA 94701

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