β-Carboline, 3,4-dihydro-7-methoxy-1-methyl · 3,4-Dihydro-7-methoxy-1-methyl-β-carboline · 3,4-Dihydroharmine · 7-Methoxyharmalan · Harmadine
SYNTHESIS: To a solution of 0.033 g 6-methoxytryptamine in 3.5 mL 0.1 N HCl, there was added 0.011 glycolaldehyde and the mixture was heated on the steam bath for 1.5 h. The solution was then made basic with 10 mL 0.5 N NaOH, and extracted with Et2O on a continuous extractor. The Et2O extracts were pooled, dried over solid KOH, the solvent removed under vacuum. The residue was an oil that crystallized to give a solid, mp 170–175 °C, presumably a hydrate of 1-hydroxymethyl-7-methoxy-1,2,3,4-tetrahydro-β-carboline. This was treated with 2.5 mL 90% H3PO4 and heated on the steam bath for 2 h. After dilution with H2O, this was made alkaline with aqueous NaOH and extracted with Et2O. The pooled extracts were stripped of solvent under vacuum, and the residue distilled to give a fraction (bp 120–140 at 0.001 mm/Hg) that weighed 0.027 g (72%). MS (in m/z): Parent ion -1, parent ion, 213, 214 (100%, 89%); 198 (29%); 201 (23%); 170 (22%); 173 (19%). IR (in cm-1): 817, 832, 916, 1037, 1139, 1172. Harmaline hydrochloride dihydrate; IR (in cm-1): 820, 841, 992, 1022, 1073, 1137.
There is a little bit of interesting history connected with the melting point of harmaline. A report appeared that described an alkaloid from Peganum harmala that looked like harmaline but which melted 18 °C too high, and so it was thought to be an isomer and was given the name harmadine. This was all cleared up a few years later when it was observed that on an open melting point block, harmaline had a mp 242–244 °C (with beginnings of sublimation at 189 °C) and harmadine had the values of 241–243 °C and 178 °C. In a capillary tube, harmaline melted at 256°C and harmadine at 257 °C. So, harmadine is now a synonym for harmaline.
DOSAGE: 150–300 mg, orally
DURATION: 5–8 hrs h
QUALITATIVE COMMENTS: (with 100 mg, orally) “I have tried this on two occasions, essentially without effect.”
(with 150 mg, orally) “In an hour and a quarter, there was a rapid-onset intoxication and I felt a little unstable. And a little bit numb. There was an unusual shimmering, in my lateral vision when I turned my head to the side. Everything was just a little bit down. Music was pretty much normal but I was missing the higher frequencies. Even light food sat heavily, and I wasn’t too hungry (and I was remembering to watch what I eat, with this monoamineoxidase stuff). Sex was difficult—probably due to some reduced sensations. I feel that this compound is unlikely to be attractive to most people, as its major effects are an intoxication with a clouding of thoughts and some disruption of musical relationships.”
(with 175 mg, orally) “After about one hour I found myself becoming relaxed and a bit sloppy. By the end of the second hour, I had peaked, and was pretty much at baseline after five hours. At the peak, three areas of disturbance were obvious. There were obvious tracers—when looking at a bright object, and moving your eyes to the side, the image of the object lags in its leaving the visual field, and it leaves in the opposite direction. As to the auditory, it seemed as if the higher frequencies of music were attenuated, and the lower frequencies amplified. And as to touch, there is a definite numbing. I had no appetite, and the little I ate didn’t taste particularly good.”
(with 200 mg, orally) “At about the two hour point I remember three things. The first was the effort to bring into reality the visual image of a face that was playing with my eyes-closed imagery. I got the mouth and, after a bit of work, I got the eyes. So I concentrated on the nose and it came into view, finally, but it was upside down. The second and third things were more easily defined. Nausea and diarrhea. Fortunately they alternated. This is not my trip of choice.”
(with 300 mg, orally) “I was in a psychotherapy environment, so there was some suggestions and leading that influenced my responses. But I have great difficulty reliving my experience, in fact I don’t remember anything. I have only disconnected images. There is a girl—me—in front of a church on a dusty road, myself at communion, receiving the Host from an invisible hand at a grandiose alter. I feel that I am going crazy. Something inside. It is not anxiety. It is not depression. It is some of each, plus irritation and disorientation. I am dead but still have to come back to life. I am facing a reality of mine that I cannot accept.”
(with 400 mg, orally) “This is Fluka material, and has a nasty taste. I felt completely immobilized and sick to my stomach. Closed eyed visuals yielded native women, ‘organic’ colors and shapes, and a black panther! I would like to do
(with 500 mg, orally) “I took a half gram of pure synthetic harmaline after fasting for over a day. The resulting nausea was greatly attenuated after I vomited. At this dose there were intense and annoying visual disturbances, and complete collapse of motor coordination. I could barely stagger to the bathroom, and for safety’s sake locomoted by crawling. Tracers and weird visual ripplings disturbed my sight with open eyes. With eyes closed, there was eidetic imagery. It had no symbolic significance, just bothersome disjointed sequences that lacked a relevant theme. They proceeded to transform so slowly (in comparison to the speed of my thought) that they were predictable and boring. Throughout the experience I just lay hoping it would end soon. It did not seem as though I had encountered intrapsychic material which was being expressed through somatic symptoms. Rather, I felt that I was struggling to metabolize a chemical disruption of my physiological functions. Although the session was not enjoyable, I was satisfied at having educated myself about the effect produced by a penalty dose of this compound.”
(with 2 g Peganum harmala seeds, ground, in capsules) “No effects.”
(with 5 g Peganum harmala seeds, ground, in capsules) “At about 1:45 tinnitus was obvious. At 2:00 precise movements were problematical and nystagmus was noticeable. Mild nausea and diarrhea, but no vomiting. I was sensitive to light and sound, and retired to a dark room. Hallucinations were intense, but only with the eyes closed. They consisted, initially, of a wide variety of geometrical patterns in dark colors, getting more intense as time went on. They disappeared when the eyes were opened. Although the loose bowels and nausea were pretty constant through the first part of the trip, I was not afraid. It was as if the “fear circuits” in the brain had been turned off. The geometric shapes evolved into more concrete images, peoples faces, movies of all sorts playing at high speed, and animal presences such as snakes. It was like vivid and intense dreaming except that I remembered most of it afterwards. In another hour things became manageable and I could go out in public. My sex drive was pleasantly enhanced, and I slept very well.”
(with 7 g Peganum harmala seeds, ground, in capsules) “Very sick for 24 hours.”
(with 20 g Peganum harmala seeds, as extract) “The is equivalent, probably, to a gram or so of the harmala alkaloids. This was ground up material extracted with hot dilute lemon juice. Within a half hour, I found myself both trippy and sleepy. Then I became quite disorientated, nauseous, and with an accelerated heart beat. I had the strong sensation of moving backwards, drifting, with faint visuals under my eyelids. Restraining the vomiting urge was an ongoing problem. I could have gone out of body quite easily, except that I was completely anchored by the nausea. After about three hours, I knew that it had peaked, and I went to sleep and experienced intense and strange dreams. The entire experience was a conflict between tripping and being sick. I want to explore this more.”
(with 28 g Peganum harmala seeds, as extract) “I sat up late one night drinking gulp after gulp of tea from about an oz. of seeds, periodically adding more water and simmering. This process took several hours, and though I had read up on harmaline, I didn’t know quite what to expect. Suddenly it hit me like a wall. It was starting to get light outside and as I shifted my gaze, zebra-like stripes of light and dark spiraled off the perimeter of the window silhouettes. Every time I shifted my focus my visual field would shudder and swirl before settling down. This visual effect had a physicality unlike those any other entheogen I'd experienced. Rather than patterns revealing greater order in sensation, these were waves of chaos revealing no particular order and urging the mind to retreat from the disturbing realm of sensation. Accompanying this was a pronounced auditory buzz. Lying down and closing my eyes I left the physical symptoms behind and explored the vivid spontaneous imaginations evoked by this state. Unfortunately, it is getting light, which made it harder to shut out the distracting world of sensation. I resolved to conduct future sessions in the night-time (and always in a quiet undisturbed place).
“A second trial was made at the same level. This time it came on very fast. That tremendous buzz on the other side of which are the wondrous realms of the subconscious. The most memorable impressions from this trip were of weird animals. I imagined myself spinning on a merry-go-round of strange winged creatures. I started to feel very sick and negotiated my way to the bathroom to face the inevitable—voiding from both orifices simultaneously. It proved cathartic, and released me to experience the state more fully. I remember traveling to jungle-like places, full of imagery of vines, fountains, and animals. Minutes seemed like hours as I roamed in these spaces. Though the sensory effects were very disturbing when I got up, given high dose level, I could easily ignore my body when laying down and traveling in my mind.”
EXTENSIONS AND COMMENTARY: Right off the bat, I must make an apology, in that I have commingled reports employing harmaline as a single chemical, with reports employing seeds from Peganum harmala. This is of course pharmacological nonsense in that harmaline is a pure chemical substance, whereas the seeds of the P. harmala contain
There is a valid reason for this commingling of the reports of the effects of this chemical and plant, however. In many people’s minds, the two materials are felt to be exclusively monoamineoxidase inhibitors, and to be interchangeable. I recently read the following bit of advice somewhere on the internet. “If you really want to get off on ’shrooms, take some harmaline or Syrian Rue seeds along with them.” This one phrase embodies a number of popular myths in the psychedelic drug subculture. Let me try to unravel this tangled knot.
Some drugs are metabolized by the removal of the needed amine function. This deamination results from the action of an enzyme system that is called a monoamineoxidase, or a MAO. If this enzyme system is inhibited, then the drug would be destroyed to a lesser extent, and would have a greater potency. The material that protects the drug from this erosion is called a monoamineoxidase inhibitor, or a MAOI. As a result, some drugs that do not show any oral activity (such as
That is the reason for the presentation of the effects of harmaline by itself, and of Peganum harmala seeds, just by themselves. They are very different from one-another, although both can be pretty rough on the body.
Now, I would like to reenter the qualitative comments mode, this time with the use of harmaline or Peganum harmala in conjunction with a second drug. In some of these examples, the inhibitor was taken ahead of the actual tryptamine, as indicated by the time statement.
FURTHER QUALITATIVE COMMENTS:
(with 20 mg harmaline and 55 mg
(with 50 mg harmaline, 60 mg
(with 80 mg harmaline, 40 mg
(with 100 mg harmaline, 120 mg
(with 150 mg harmaline, 35 mg
(with 150 mg harmaline, 80 mg
(with the extract of 3 g Peganum harmala seeds, 40 mg
(with the extract of 5 g Peganum harmala seeds, 20 mg
(with 70 mg harmaline, 10 mg
(with 80 mg harmaline, 10 mg
(with 150 mg harmaline, 25 mg
“I started to come ‘down’ into a more differentiated consciousness, and the first thing I felt was a powerful, aggressive sexual feeling. I was not wearing any clothes and I spent a long time, over an hour, writhing around, occasionally uttering phrases of one or three or four words of a very hostile and/or sexual nature. I remember saying I hated my sitter (a female) and God, but it was quite clear that it was the sexual/maternal image of the sitter that I hated as something that I desired and felt dependent upon while resenting that I needed something I did not have within myself. The next phase found me physically calm and quiet. Finally, after four hours, I felt sleepy and comfortable. I ate well, and was in a good mood.
“I do not feel that taking a higher dose orally would necessarily have pushed me through to the state achieved by smoking because the onset was so, so slow. I don’t think I’ll repeat this combination.”
(with 150 mg harmaline, 200 mg
(with 100 mg harmaline, 60 mg
(with 150 mg harmaline, 100 mg
FURTHER EXTENSIONS AND COMMENTARY: There is a fascinating unanswered question that I had to ask myself a little while ago. It is a question that, if ever answered accurately, just might throw the entire area of the pharmacology of harmaline into a delightful disarray. I received a small quantity of documented seeds of Syrian rue and I was curious to see, in my hands, what its alkaloid content was. This is, after all, a well known source rapidly increasing in popularity as the inhibitor component of ayahuasca. So I ground a few of them up in a mortar under DMF and carbonate, spun down the extract, dissolved a drop of it in a milliliter of 90:10 toluene/butanol, and shot a microliter into the GCMS. As expected, there were two major peaks, and an intriguing scatter of small things. The spectrum of first was clearly that of harmaline, and of the second, that of
Then, to tidy up a bit and make absolutely sure of the relative retention times, I decided to run standards from my reference collection. Reference
Three explanations popped into mind. (1) Maybe the P. harmala itself. Maybe the analytical tools at the time were inadequate to detect and identify this amount of harmine as an impurity. This is not comfortable, in that these two alkaloids were first isolated, and separated from one-another, from plant sources some 150 years ago. I am sure my sample is not that old. I am not sure that even E. Merck AG is that old. The tools of analysis have been around a long time. Anyway, I wrote to them, and they answered me with the elliptical comment stating that they had never had harmaline in their catalog, only harmine. And thus, they would have no way of knowing what was in the bottle. Of course they could have distributed research samples of many things, of stuff that was never in their catalog, but by replying in this way they are absolved of all guilt. And of all legal responsibility as well, of course. OK.
This leaves (3). Maybe over the years, harmaline spontaneously loses a molecule of hydrogen, and becomes Banisteria caapi (now known as Banisteriopsis caapi). The herbarium specimens he was looking at had been collected by the 19th century plant explorer Richard Spruce in the Rio Negro area of South America and had, after a few years of storage in a moist and mildewy hut a few miles down river, been rediscovered and sent on to the Kew Botanical Museum where they had quietly rested for over a hundred years. When Holmstedt worked them up some 30 years ago, he reported that the alkaloid content was 0.4%. This was virtually identical to a newly collected, botanically verified specimen of Banisteriopsis caapi which he analyzed at the same time and found to contain 0.5% alkaloids. The latter material contained, as described by many authors, the main alkaloids harmine, harmaline and
How can this enigma be answered? Put away a sample of pure harmaline, with its spectral identification, onto the shelf for 50 or 100 years, and then re-analyze it? Who knows, but what might be needed for this conversion is heat, or a bit of iron catalyst, or some unknown species of South American mold. Acid is certainly known to promote this oxidation. It would be very much worth while to answer this question because some, perhaps much, of the results of human pharmacological studies that involve harmaline as a metabolic poison, may be influenced by the independent action of
If indeed the use of Peganum harmala becomes increasingly popular as a harmaline source, some help might be useful for those who do not have balances and need to call upon volumes instead. I decided to make an equivalency table between weights, and volumes, and quantities, and laboratory numbers, and kitchen things, so that some consistency might be found in the measurement of the botanical materials that are being used. In short, how heavy is something or how bulky is it? My starting point was the most frequently used tool that is mentioned, continuously, in the lay press dealing with drugs and drug use. It is the teaspoon. How much stuff is there in a teaspoon? Just how big is a teaspoon? What is a teaspoon? Is it a small semi-spherical metal scoop hanging from a ring that has other scoops of different dimensions attached, that is found in the knife and cork-puller drawer in the kitchen? Or is it a schluppy thing, with an artistic handle on it, that adds sugar to your coffee and does the stirring? Do you heap stuff up on it, or do you level it off by smoothing it flat with your finger? The dictionary says that a teaspoonful contains exactly 1.333 fluid drams. Oh wow! Let’s look it up. You will discover that this is a total cop-out if you read the dictionary definitions of dram: (1) 1.771 grams if you are using the avoirdupois system, or (2) 3.887 grams if you are using the apothecaries system. So, how does a non-pharmacist person, without an analytical scale or an immediate command of the avoirdupois versus apothecaries vocabulary, measure a wanted quantity of Peganum seeds?
I would suggest using the following scale, remembering that with water weights can be easily interchanged with volumes, since water has a weight that is equal to its volume. In both of these scales, the water and the rue, the teaspoon is the small semi-spherical thing in the cork-puller drawer, leveled off:
—This is for water—
|1 teaspoon water =||0.16||ounces (5 grams)|
|3 teaspoons||=||1||tablespoon||=||0.5||ounce (14 grams)|
|2||tablespoons||=||1||ounce (28 grams)|
|4||quarts = 1 gallon|
or, as I had learned as a childhood rhyme; a pint’s a pound, the world around.
You must remember, this volume thing has its own traps. When you start using the volume measurement for things such as seeds, or bark, or leaves, or other biological things that are not of the density of water, they possess varying degrees of fluffiness, and the weights will be less than the volumes. The Rosetta stone translation that is appropriate here is based on the fact that the Peganum harmala seeds are just over half the density of water. And, since they may contain from 2 to 6% its weight of alkaloids, the following equations are useful:
—This is for the seeds of Syrian rue—
|1 teaspoon rue seeds =||3||grams||=||60–180 mg alkaloids|
|1 tablespoon rue seeds =||9||grams||=||200–600
|1 large (
with ground rue seeds =
|0.7||gram||=||15–45 mg alkaloids|
But do remember, with the harmaline and Peganum harmala, you are also accepting an equal weight of quinazoline alkaloids with pharmacological properties that are quite different from those of the carbolines.
20 Jun 2018 · · Isomer Design
About TiHKAL · info
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 align precisely with the printed version. Text appears to have been inserted, deleted, or changed at various points. Where the two are seen to diverge both the Erowid and print versions are given. Sharp-eyed readers are encouraged to report novel discrepancies.
As with PiHKAL, I’ve again attempted to reproduce the typographic style of the printed edition. I’ve again 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.
“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.”
The copyright for Book I of TiHKAL has been reserved in all forms and it may not be distributed. Book II of TiHKAL may be distributed for non-commercial reproduction provided that the introductory information, 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.
Though 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,
Berkeley, CA 94701
510 · 934 · 4930 (voice)
510 · 934 · 5999 (fax)