#126 METHYL-DMA SYNTHESIS: To a stirred solution of 28.6 g methylamine hydrochloride in 120 mL MeOH there was added 7.8 g 2,5-dimethoxyphenylacetone followed by 2.6 g sodium cyanoborohydride. HCl was added as needed to maintain the pH at about 6. The reaction was complete in 24 h, but was allowed to stir for another 3 days. The reaction mixture was poured into 600 mL H2O, acidified with HCl (HCN evolution, caution) and washed with 3×100 mL CH2Cl2. Aqueous NaOH was added, making the solution strongly alkaline, and this was then extracted with 3×100 mL CH2Cl2. Removal of the solvent from the pooled extracts under vacuum gave 8.3 g of a clear, off-white oil that distilled at 95–105 °C. at 0.25 mm/Hg. The 6.5 g of colorless distillate was dissolved in 25 mL IPA, neutralized with concentrated HCl, and then diluted with anhydrous Et2O to the point of cloudiness. As crystals formed, additional Et2O was added in small increments, allowing clearing crystallization between each addition. In all, 200 mL Et2O was used. After filtering,Et2O washing, and air drying, there was obtained 6.2 g of 2,5-dimethoxy-N-methylamphetamine hydrochloride (METHYL-DMA) as fine white crystals with a mp of 117–118 °C. The mixed mp with (114–116 °C) was depressed to 96–105 °C. An alternate synthesis gave the same overall yield of an identical product, but started with 2,5-DMA. It required two synthetic steps. The free base amine was converted to the crystalline formamide with formic acid in benzene using a Dean Stark trap, and this intermediate was reduced to METHYL-MDA with LAH.
DOSAGE: above 250 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 250 mg) “There is a slight paresthesia at about 45 minutes, an awareness on the surface of the skin as if I had been touched by a cold draft of air. But nothing more. At three hours, I am completely out, if I was ever in. In the evening I assayed 120 milligrams of , and it barely produced a threshold effect, so the two materials might be seeing one another.”
EXTENSIONS AND COMMENTARY: This is a difficult compound to pin down in the anthology of drugs. For some reason it has intrigued several independent, quiet researchers, and I have accumulated a number of interesting reports over the years. One person told me that he had felt nothing at up to 60 milligrams. Another had found a threshold at 50 milligrams, and had complete and thorough experiences at both 150 and 200 milligrams. Yet another person described two incidents involving separate individuals, with intravenous administrations of 0.2 mg/kg, which would be maybe 15 or 20 milligrams. Both claimed a real awareness in a matter of minutes, one with a tingling in the genitalia and the other with a strange presence in the spine. Both subjects reported increases in body temperature and in blood pressure. Apparently the effects were felt to persist for many hours.
There is an interesting, and potentially informative, convergence of the metabolite of one drug with the structure of another. Under , mention was made of a bronchodilator that has been widely used in the treatment of asthma and other allergenic conditions. This compound, 2-methoxy-N-methylamphetamine is known by the generic name of methoxyphenamine, and a variety of trade names with (Upjohn) being the best known. The typical dosage of methoxyphenamine is perhaps 100 milligrams, and it may be used several times a day. It apparently produces no changes in blood pressure and only a slight cardiac stimulation. And one of the major metabolites of it in man is the analogue with a hydroxyl group at the 5-position of the molecule. This phenolic amine, is just a methyl group away from METHYL-DMA; it could either be methylated to complete the synthesis, or METHYL-DMA could be demethylated to form this phenol. There is plentiful precedent for both of these reactions occuring in the body. It is always intriguing when drugs which show distinctly different actions can, in principle, intersect metabolically at a single structure. One wonders just what the pharmacology of that common intermediate might be.
Three additional N-methylated homologues of known psychedelics warrant mention, but do not really deserve separate recipes. This is because they have had only the most cursory assaying, which I have learned about by personal correspondence. All three were synthesized by the reduction of the formamide of the parent primary amine with LAH. (or N-methyl-3,4,5-trimethoxyamphetamine) had been run up in several trials to a maximum of 240 milligrams, with some mental disturbances mentioned only at this highest level. (or N-methyl-2,4,5-trimethoxyamphetamine) had been tried at up to 120 milligrams without any effects. (or N-methyl-2,4,6- trimethoxyamphetamine) had been tried at up to 30 milligrams and it, too, was apparently without effects. These are reports that I have heard from others, but I have had no personal experience with them. Those that I can describe from personal experience are entered separately as recipes of their own. And there are many, many other N-methyl homologues which have been prepared and characterized in the literature, and have yet to be tasted. So far, however, the only consistent thing seen is that, with N-methylation, the potency of the psychedelics is decreased, but the potency of the stimulants appears to be pretty much maintained.
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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