SYNTHESIS: A suspension of 10 g tryptamine base in 10 g butyl formate was held at reflux for 24 h. The resulting clear solution was stripped of volatiles under vacuum, and the residue partitioned between dilute HCl and CH2Cl2, and the aqueous phase extracted twice with additional CH2Cl2. The pooled organic extracts were washed once with dilute aqueous HCl, once with dilute aqueous NaOH, and the solvent removed under vacuum to give a black oil. This was distilled at the KugelRohr to give 9.05 g (77%) of N-formyltryptamine as a clear oil, boiling at 170–190 °C at 0.1 mm/Hg which set to a glass. MS (in m/z): indolemethylene+ 130 (100%); 143 (57%); parent ion 188 (15%). This amide slowly crystallized on standing, but was used as the glass in the reduction described below.
A solution of 1.88 g N-formyltryptamine in 40 mL anhydrous Et2O was added to a 60 mL of a 1 N solution of LAH in THF, well-stirred under argon, and was held at reflux for 24 h. After cooling to room temperature, the excess hydrid hydride was destroyed by the addition of 20 mL of 50% aqueous THF. The resulting solids were removed by filtration, and the filter cake washed repeatedly with damp THF. The basic filtrate was stripped of solvent under vacuum to give 1.39 g of a pale oil which started to crystallize. After distillation at 135–145 °C at 0.1 mm/Hg, there was obtained 1.22 g (70%) of N-methyltryptamine as a white oil that which spontaneously set up to white crystals of the free base. These rapidly darkened on exposure to air. The infra-red spectral fingerprint was IR (in cm-1): 740, 1018, 1103, 1132, 1161. The literature mp is 90 °C. A 0.22 g sample of darkened base in 1.0 g IPA was neutralized with concentrated HCl (using external moistened pH paper as a titration guide) with the development of an intense blue-green color with the addition of each drop of acid. The acidified solution (now a stable blue-green color) was diluted with
diethyl Et2O (about 1 mL). This cloudy solution, upon scratching, set to crystals which, upon removal by filtration, Et2O washing, and air drying to constant weight, weighed 0.18 g and had a mp of 178–180 °C. The IR of N-methyltryptamine hydrochloride (NMT) IR (in cm-1): 748, 850, 1009, 1104, 1119, 1136. MS (in m/z): C2H6N+ 44 (100%); indolemethylene+ 130, 131 (51%, 61%); parent ion 174 (2%).
EXTENSIONS AND COMMENTARY: N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide N-methylindol-3-ylglyoxalylamide (mp 223–224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175–177 °C from EtOH) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above.
To my knowledge there have been no reports of oral activity of NMT, although its wide availability from botanic sources has encouraged some explorers to assay it. I have had one report that the smoking of 50–100 mg gave visuals that lasted for maybe 15 seconds. The N-hydroxy analogue has been noted as being found in plants, in the “DMT is Everywhere” chapter.
McKenna, DJ. Monoamine odixase inhibitors in Amazonian hallucinogenic plants: Ethnobotanical, phytochemical, and pharmacological investigations. Ph. D. Thesis, University of British Columbia, BC, Canada, 26 Apr 1984. 12211 kB.
Gornez-Jeria, JS; Morales-Lagos, D; Cassels, BK; Saavedra-Aguilar, JC. Electronic structure and serotonin receptor binding affinity of 7-substituted tryptamines QSAR of 7-substituted tryptamines. Quant. Struct.-Act. Relat., 1986, 5 (4), 153–157. 577 kB. doi:10.1002/qsar.19860050404
Gartz, J. Biotransformation of tryptamine derivatives in mycelia cultures of Psilocybe. J. Basic. Microbiol., 1989, 29 (6), 347–352. 357 kB. doi:10.1002/jobm.3620290608
Peroutka, SJ; McCarthy, BG; Guan, X. 5-Benzyloxytryptamine: a relatively selective 5-hydroxytryptamine1D/1B agent. Life Sci., 1 Jan 1991, 49 (6), 409–418. 556 kB. doi:10.1016/0024-3205(91)90582-V
Khalil, EM; Angelis, JD; Cole, PA. Indoleamine analogs as probes of the substrate selectivity and catalytic mechanism of serotonin N-acetyltransferase. J. Biol. Chem., 13 Nov 1998, 273 (46), 30321–30327. 247 kB. doi:10.1074/jbc.273.46.30321
Jensen, N. Tryptamines as ligands and modulators of the serotonin 5-HT2A receptor and the isolation of aeruginascin from the hallucinogenic mushroom Inocybe aeruginascens. Ph. D. Thesis, Georg-August-Universität zu Göttingen, Göttingen, Germany, 4 Nov 2004. 2268 kB. Referent: Prof. Dr. H. Laatsch; Korreferent: Prof. D. E. Nichols.
Fontanilla, D; Johannessen, M; Hajipour, AR; Cozzi, NV; Jackson, MB; Ruoho, AE. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science, 13 Feb 2009, 323 (5916):,934–937. 529 kB. doi:10.1126/science.1166127
McIlhenny, EH; Pipkin, KE; Standish, LJ; Wechkin, HA; Strassman, R; Barker, SA. Direct analysis of psychoactive tryptamine and harmala alkaloids in the Amazonian botanical medicine ayahuasca by liquid chromatography–electrospray ionization-tandem mass spectrometry. J. Chromatogr. A, 18 Dec 2009, 1216 (51), 8960–8968. 450 kB. doi:10.1016/j.chroma.2009.10.088
Meyers-Riggs, B. Grid biosynthesis of psilocybin. countyourculture: rational exploration of the underground, 5 Dec 2011.
Barker, SA; McIlhenny, EH; Strassman, R. A critical review of reports of endogenous psychedelic N,N-dimethyltryptamines in humans: 1955–2010. Drug Test. Anal., 2012. 270 kB. doi:10.1002/dta.422
Meyers-Riggs, B. N-Alkylated tryptamines. countyourculture: rational exploration of the underground, 10 Mar 2012.
This version of Book II of TiHKAL is based on the Erowid online version created by Bo Lawler with the help of Erowid, from content generously provided in electronic format by the Authors.
The Erowid online version does not always match the printed version—I’ve found over 300 inconsistencies. Text has been inserted, deleted, or changed at various points. Perhaps the Erowid version was created from an earlier (or later) draft? In several places the Erowid version is plainly wrong; elsewhere it’s a tougher call. I don’t claim to have found every discrepancy; in those cases I have found, both the Erowid and print versions are given and marked as such. I would be grateful if any sharp-eyed readers would report any I have missed.
As with PiHKAL • info, I’ve again attempted to reproduce the typographic style of the printed edition. And again, I’ve also made minor changes to some chemical names in line with current nomenclature practice, and in the hope of aligning with more readers’ searches. Typically the change is little more than expanding a prefix and setting it in italics. The errata and changes page has further details.
“I would like to take a moment to reiterate that 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
The Copyright for Part 1 of TiHKAL has been reserved in all forms and it may not be distributed. Part 2 of TiHKAL may be distributed for non-commerical reproduction provided that the introductory material, copyright notice, cautionary notice and ordering information remain attached.
TiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of tryptamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Although Sasha and Ann have put Book II of TiHKAL 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.
TiHKAL (ISBN 0-9630096-9-9) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.Transform Press,