SYNTHESIS: There was prepared a solution of 25.75 g indole in 100 mL DMF. A second solution was also prepared by cooling 80 mL DMF in an external ice bath (internal temperature about 12 °C), stirring well, and adding 20 mL POCl3 dropwise over the course of 30 min. This was then warmed to 25 °C and the first solution of indole in DMF was added dropwise (with continued stirring) over an additional 30 min. Stirring was continued for yet another 45 min, during which time the temperature was raised to 40 °C. Yellow solids formed during this period. The reaction mixture was poured onto chipped ice which produced a clear red solution. This was made basic with the addition of 200 mL 5 N NaOH which allowed the separation of a yellow solid. This was diluted by the addition of 200 mL hot H2O and, after cooling again, the product was removed by filtration and washed with cold H2O. This can be recrystallized from aqueous DMF to yield, after air drying, 24.5 g (84%) of indole-3-carboxaldehyde as faint orange needles.
A solution of 4.35 g indole-3-carboxaldehyde in 17.2 mL nitroethane was treated with 0.77 g ammonium acetate and heated, with occasional swirling, on the steam bath for 2.5 h. The excess reagent was removed under vacuum and the resulting yellow solids washed with H2O and air dried. Trituration under 25 mL dry MeOH, filtration, and air-drying gave 5.22 g (86%) 1-(3-indolyl)-2-nitropropene-1 as a yellow powder with mp 190–192 °C.
A suspension of 10.7 g LAH in 100 mL anhydrous THF was placed under an inert atmosphere, stirred, and treated dropwise with a solution of 10 g 1-(3-indolyl)-2-nitropropene-1 in anhydrous THF over the course of 2.5 h. The reaction mixture was brought to reflux temperature, held there for 2 h, and then returned to room temperature. The excess hydride was destroyed with an aqueous THF solution (80 mL of 25% solution) and there was then added 10 mL of 50% NaOH. There was added 150 mL Et2O, and the stirring was continued until no more solids formed. The reaction mixture was filtered and the filter cake washed with 150 mL Et2O. The filtrates and washings were combined, dried over K2CO3, and the solvent removed under vacuum. The residue weighed 9.2 g and was distilled at 130–140 °C at 1 mm/Hg to give a white oil that crystallized and had a mp of 96–98 °C. This was recrystallized from an ethyl acetate/petroleum ether mixture, and had a mp of 97–100 °C. The yield was 6.3 g (73%). IR (in cm-1): 750, 818, 911, 933, 1093, 1111. MS (in m/z): C2H6N+ 44 (100%); indolemethylene+ 130, 131 (44%, 43%); parent ion 174 (2%). A sample dissolved in 10 volumes of methanol, treated with one equivalent of glacial acetic acid, and taken to dryness under vacuum gave the acetate salt which, on recrystallization from ethyl acetate and air drying to constant weight yielded the product α-methyltryptamine (α-MT) as fine white crystals with a mp of 143–144 °C. The fumarate salt, formed by the addition of ethyl acetate to a hot solution of free base α-MT in methanol which had been neutralized with fumaric acid, was isolated as fine white needles with a mp of 200–203 °C.
DURATION: 12–16 hrs h
QUALITATIVE COMMENTS: (with 15 mg, orally) “I got a strong psychedelic experience that lasted about twelve hours, but an unexpected relief from my chronic depression that lasted for four days.”
(with 20 mg, orally) “Nothing happened for three hours—I thought I had drawn a blank. Then I became a little uncomfortable, restless, this delayed action is new to me. I feel completely washed out, exhausted. And I had a hang-over the next morning.”
(with 30 mg, orally) “It felt a little like speed, strong speed. Yet I found myself yawning and in sort of a dreaminess state and quite lethargic. It lasted a long time.”
(with 30 mg, orally) “Effects were first noted in just over an hour, a general numbness and a mild loss of motor coordination. This all became more pronounced over the next half hour, but my thoughts remained clear. A hand tremor and jaw tightness persisted throughout the experience. Music was OK but I didn’t really connect with it. There were no open or closed-eye visuals, but there was a moderate light sensitivity that lasted the day, and the visual field was altered such as the outside world did indeed appear unreal and alien. Were there any positive aspects to the day? I talked with a friend for two hours on the telephone, with ease. And I had no appetite. But there seems little else to recommend this compound. I slept well at the 12th hour.”
(with 80 mg, orally) “I shot up in an hour, and by another hour I was vomiting worse than with mescaline. Absolutely no visuals, no hallucinations, but extreme depersonalization. Thirteen hours into this and it is still go, go, go. Out with a bit of pot.”
(with 100 mg, orally) “There was pupillary dilation, jaw clenching, tachycardia and vomiting. Too much. But I really liked this compound at lower dosages.”
(with 4 mg, smoked) “It burns and smells bad. It took quite a while to come on. After a half hour, BINGO, there was a very slow building of a definite psychedelic. It builds slowly but strongly for another few hours to a plateau at maybe four hours after which a very slow decline sets in. But even after 18 hours following input, and after 7 hours of sleep, I awoke still feeling the effects.”
(with 5 mg, smoked) “Qualitatively it was milder and less intense than mushrooms, but much longer lived. Not complex, but just a lot of very good spirit, energetic feeling, enhanced colors, attractive rhythms in music. Party stuff.”
(with 6 mg, smoked) “Onset was immediate, with heart racing, enhancement of surroundings. Taste? Pee-yew!”
(with 10 mg, smoked) “While there are no true visuals to speak of, the overall picture of things seemed grainy—as if filmed on low quality color 16mm film. There is an energized eeriness about inanimate objects. This lasted three hours.”
(with 20 mg, smoked) “I inhaled several hits from my vaporizer and sat back. I felt head-pressure and uneasiness, then suddenly I became very fast. My mind was moving fast, and my body was speeding along with it in an unconscious way. Several hours into it, I began to notice more of a psychedelic effect beginning to manifest. It seemed as if the speedy part was becoming less predominant and the psychedelic visual effects were starting to kick in. I went back to my room to watch the distinctive waves of a soft red/orange visuals They were similar to colors of LSD. It gradually increased to a level of intensity similar to perhaps 0.5–1.0 g P. cubensis, and after several more hours it was clear that I had reached the plateau. Feeling fairly tired and ready for bed, I decided to call it a night. Quite to my surprise, when I awoke four hours later I was at the same level as when I went to sleep. Gradually over the next day I returned to baseline and I was left feeling quite euphoric with a pleasant afterglow.”
EXTENSIONS AND COMMENTARY: In the 1960’s there was quite a bit of interest in a couple of pharmaceutical houses with the indole analogues of amphetamine. Both the alpha-methylated tryptamine (this compound, α-MT) and the alpha-ethylated homologue (α-ET, see its separate recipe) were found to be effective monoamine oxidase inhibitors, and both were clinically studied as potential antidepressants. The ethyl compound became a commercial drug, offered by the Upjohn Company as Monase, but now is considered to be without medical use and is a Schedule I drug. It is interesting that this methyl compound, α-MT was also a medically available antidepressant in the Soviet Union in the 1960’s and was sold under the name of Indopan, in 5 and 10 milligram tablets.
There is quite obviously a wide range of reported effect described for α-MT, indicating much individual variability. For some it has a fast onset, for others a slow one. Some find it a good psychedelic, others are disturbed by the negative physical side-effects. This is all a bit reminiscent of harmaline, where the spectrum of responses also range from 1 to 10 on a scale of 1 to 10. Perhaps this is a reflection of the monoamineoxidase inhibition property, and if so, perhaps low levels of α-MT might serve the harmaline role of inhibiting the metabolic destruction of DMT in some form of a pharmahuasca.
I have always been intrigued by a fascinating bit of speculation. Ken Kesey, of “One Flew over the Cuckoo’s Nest” fame, had his own nest in a log cabin down in La Honda, back in the ’60’s. This was given fame mostly by Tom Wolfe’s “The Electric Kool-Aid Acid Test” The Electric Kool-Aid Acid Test where it was well described. At that time, Kesey served as an experimental subject for a number of studies involving psilocybin, Ditran, and α-MT. Shortly after these were completed, he left and took the role of “The Chief” of his band of “Merry Pranksters” who traveled far and wide around the country U.S. in the now famous bus, the “Further.” The stories of their broad and well advertised use of LSD are legion. I had heard as a rumor that the research supply of α-MT had disappeared at about the same time, and the thought occurred to me that maybe the drug consumed in the tour was not LSD but α-MT. Or maybe today one, and tomorrow the other. I made gentle inquiry of the research director there, whom I knew personally, if this might be so, and his opinion was that the material used by Kesey and the pranksters was probably LSD, as it was so widely available at that time.
There is another parallel to the ethyl homologue, α-ET. In the commentary under α-ET, I had mentioned how industry was benefiting economically in the War on Drugs, by charging inflated prices for reference and research samples. Here, there just might be political counterpart. There are several commercial sources for α-MT, with catalog prices ranging from $50 to $150 per gram. I bought a gram from Acros Organics and it was delivered with dispatch. I also received the MSDS sheet (Material Safety Data Sheet, a listing of physical hazard information now required to accompany all chemicals purchased) and it not surprisingly had no mention of any known hazard. Imagine my surprise when I received the invoice only to find that there as a $6 surcharge as a hazardous shipping charge. Some three 800-number phone calls later, I got to a person at Fisher Scientific who told me that this was a result of the State of California placing this compound on a Classification #110 listing. I had previously received solvents from Acros, that were inflammable, volatile, bad smelling and rather toxic, and had never before had to pay a hazard fee. I suspect that someone in Sacramento has discovered that this compound has a wide acceptance as a stimulant and somewhat psychedelic, and is effectively capatalizing capitalizing on it before it becomes illegal. One of the commercial suppliers, a mail-order operation called CRSB, provides drug precursors (not illegal) and actual drugs (not illegal) as long as no illegal use will be made of them. The demand for α-MT is very high, second only to gamma-butyrolactone which can be converted to GHB with sodium hydroxide (the #3 item in their sales volume listing).
There is some interesting biochemistry and pharmacology all around the edges of α-MT. The 4-hydroxy analogue of α-MT has been looked at in human subjects. It is reported to be markedly visual in its effects, with some subjects reporting dizziness and a depressed feeling. There were, however, several toxic signs at doses of 15 to 20 milligrams orally, including abdominal pain, tachycardia, increased blood pressure and, with several people, headache and diarrhea. The 5-hydroxy analogue of α-MT is also a well-studied compound, but not to my knowledge in man. It can be called α-methylserotonin (α-M-5-HT or α-MS), and it is an effective inhibitor of 5-hydroxytryptophan decarboxylase which is the immediate precursor to serotonin (5-HT). The amino acid tryptophan, without the 5-hydroxy group but with an α-methyl group, is α-methyltryptophan, and it is readily metabolized by the rat to α-MS. In the pineal, it mimics serotonin rather than melatonin, and there is no evidence that it is acetylated on to a melatonin analogue. This α-methyl blocking of the amine group from metabolic deamination represents a half-way step in the modification of serotonin to allow it to enter into the central nervous system, i.e., the protection of the amine group from deamination because of its alpha-methyl substituent. The rest of the needed modification is the methylation of the 5-hydroxy group as well. This yields alpha,O-dimethylserotonin which allows the entry of this serotonin-like product (α,O-DMS) directly into the brain. In all this casual use of the Greek letter alpha to indicate the carbon atom next to the nitrogen atom of the tryptamine side-chain, readers of the very old literature should remember that the letter alpha used to be used to indicate the 2-position of the pyrrole ring.
A few more compounds can be considered as part of this territory. The addition of a methyl group to the indolic 1-position gives rise to 1,α-DMT. This has been prepared in the conventional way from the 1-methylindole-3-carboxyaldehyde via the intermediate nitrostyrene reduced, in turn, with LAH. It represents the MLD-41 to LSD relationship, where there was some three fold drop in potency. The α,α-dimethyl tryptamine homologue (α,α-DMT) is also known. It represents the phentermine to amphetamine relationship where, again there is a three fold drop in potency. It would be a fair hypothesis to expect either of these “DMT’s” to be active stimulants at reasonable dosages, but neither have been explored in man. The analogue with the methyl group relocated to the indolic 4-position (4,α-DMT) has been looked at in man. At an oral dose of 20 milligrams, there are reports of feelings of unreality. External body signs include flushing, muscle tightness, and eye dilation.
And there are five possible chain relocation, from the normal 3-position to the 2, the 4, the 5, the 6 or the 7-positions. All five “alpha-methyltryptamine” isomers are known, but only one is known to be active in man as a CNS active material. This is the 5-isomer, 5-(2-aminopropyl)indole or 5-IT, which, at 20 milligrams orally, is a long-lived stimulant producing increased heart-rate, anorexia, diuresis, and slight hyperthermia for about twelve hours.
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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,