Pihkal

by Alexander Shulgin

  milligrams it gave me a 1.5 plus.

  The treasure turned out to be MEM, with the ethoxy in the 4-position. Perhaps the term, "4-position," which comes up again and again in this chemical story, may be now a little less mysterious. Again, it is the place on the ring, opposite the rest of the big collection of atoms on the molecule, where the action takes place. There is true magic there, and it was with the MEM that it first became apparent. MEM was clearly active at 10 milligrams. The activity was only marginal, but it was unquestionable.

  Just before a full half-hour had passed following the taking of 10 milligrams, I felt a dizziness, and had to get up and move about to offset some tension in my legs. There was no nausea.

  About 15 minutes later, I was clearly intoxicated (in the ethanol sense) but there were absolutely no apprehensions. There was a very slight eye dilation. From the two-hour period on, at least at this dosage, I felt that I was pretty much repairing mentally, but could not seem to shake a slight residual physical distress. I knew I had an active material here, and that I should proceed with caution.

  The first thing I did was to give a good supply of it to my psychiatrist friend, Paris Mateo, with whom I had worked with TMA. He had a long history of fruitful investigations into the uses of psychoactive drugs of various kinds in therapy. Paris explored MEM with seven willing patients.

  He reported the effective range to be from 10 to 40 milligrams. He concluded that it was certainly more potent than TMA-2 quantitatively, and that it produced a more defended attitude than TMA-2 in his patients. My friend the psychologist, Terry Major (also familiar with TMA), assayed MEM at 20 milligrams, and reported the chronology as peaking somewhere around the third hour, and out at about the eighth hour. The qualitative effects, he said, were along the psychedelic line (color, visual intensity, wavering of the visual field, emotional euphoria), but that he was also aware of slight but real extra-pyramidal tremors.

  This was clearly the most active of the mono-ethoxy compounds. I wrote up a short note in which I described all eight possible permutations of M's and E's, and sent it to the Journal of Medicinal Chemistry. It was accepted.

  I explored MEM quite thoroughly in the 20 to 30 milligram area, in these early years, and found it to be a most impressive psychedelic. In 1977,1 went up to 60 milligrams and found it not to be the profound self-analysis drug I had hoped it would be, at least not for me. But I also became aware that I was a little bit insensitive to this material, so I learned to recommend dosages in the 20 to 30 milligrams area for other explorers.

  From late 1977 to mid-1980,1 did eleven experiments with MEM with a total of nine members of my research group (usually in threes and fours), all in the 25 to 50 milligram range. In general, we found that there was always some body discomfort, extreme anorexia (loss of appetite) and frequent reports of color enrichment and eyes-closed fantasy. The material insists on being complex, but seems nonetheless to leave you in charge. In general, the effects drop off between the sixth and tenth hour, but sleep - even some hours later - can include disturbing dreams. It was not too restful for a number of the experimenters.

  I abandoned MEM in 1980, choosing to spend my time on other more intriguing compounds, but not before a couple of important experiences had taken place with the drug. One involved another psychiatrist friend of mine, who was so impressed with his observations of an opening of easy communication, that he decided to spin MEM into his practice, in a very limited way, using it with those patients he felt might benefit from it.

  The other was a day I will never forget, a day that I spent with a woman in her late forties, Miriam 0. She had had a few, largely unimpressive, earlier experiences with psychedelics, but her interest in working with psychoactive drugs had been rekindled by an experience with MDMA. She wanted to try something new, and I suggested MEM. I met her in Marin County one clear and not very cold December morning. I took 50 milligrams and she took 25. I had already asked her if there was any particular question she wished to address, and she said no, it was simply to be an adventure in altered spaces. The results were a reminder of the old but good maxim in the area of psychedelics: there are no casual experiments.

  At about the one hour point, we were well into the effects, around a plus one and a half. We wandered into the Green Gulch Zen Center just in time to attend a half-hour meditation session and to buy a loaf of home-baked bread. Thence on to Muir Beach and to a rolling plus-three.

  For a while, it was theater time. Sam Goldwyn was running the show, directing Miriam's poses and gestures, her entrances and exits, while I played the role of the laughing audience. When we were tired of making movies, we started up toward the top of a hill overlooking the Pacific Ocean, with a broad view of the surf below. After climbing a bit, we turned toward the ocean and came upon a barbed-wire fence. I suggested we crawl through it and find a place to sit and look at everything and talk

  " can't," was the reply, "My legs don't seem to work."

  Her step was wobbly, and once she had reached the fence, it was clear she was having a really difficult time getting a foot raised to stick it between the two strands of wire.

  "I've lost control of my bottom half!"

  I helped her through, despite her apparent inability to make anything work too well, and we reached a sitting down place on the grass and sand.

  "My legs are paralyzed," Miriam said, "I'm being poisoned, and I want out."

  Something was developing, and I didn't know what it was she was headed for, but this "paralysis" and "poisoning" was obviously part of what was on its way up to the surface.

  "Well," I offered, rather unsympathetically, "If you really want to dump the poison, concentrate it into one place, and if it's high enough, you can vomit it out, and if it's low enough, you can shit it out."

  "I'm not fooling around," Miriam protested, "I'm really being poisoned and I want out."

  "Then get yourself out. You're in charge."

  There was no comment for a minute. Then she said it.

  "Can you give yourself cancer?"

  "You certainly can. Almost everyone who has cancer has gotten it for some reason that seems quite adequate. Where is yours?"

  "In my stomach."

  With her "paralyzed" legs stretched out in front of her, she gently touched her stomach to indicate the site of the enemy. She then unfolded one of the most complex stories I had ever heard, all of which boiled down to the fact that she'd had stomach cancer for some time, and always carried around in her purse some thirty Dilaudid tablets, so that if the pain got too much, she could end the whole thing.

  I asked the only question that occurred to me.

  "Why do you need cancer?"

  That broke the dam. She dissolved in tears and blurted out her secret. Many years before, her mother had suffered from cancer of the stomach and was in such intractable pain that/ finally, Miriam and her stepfather had smothered her with a pillow, releasing her from the agony. She was a teenager and she had helped kill her mother. She told me that she'd had total amnesia for all events in her life from that time until her early 20's.

  I wept with her.

  Later, we retraced our steps down the hill, reintegrating by revisiting each locale along the way which represented stages of the drug development, until we were back to the point where the entire experiment had started.

  Of course, Miriam did not have cancer of the stomach. She also had no residual leg paralysis.

  What she emerged with was an understanding of how the repressed grief and guilt had planted itself in her own body, giving symptoms which were signals to her of something dark which needed to be exposed and opened up to consciousness before she did, indeed, succeed in giving herself her mother's cancer.

  When we talked again, several days later, she told me - almost casually - that she had thrown away the Dilaudid. I could only say a heartfelt thank you.

  I had developed a keen respect for MEM.

  CHAPTER 9. DOM

  DOM appeared on the street i
n the 1960's under the name of STP and it proved to be for quite a while my hair shirt or, as Albert Hofmann would say later about his discovery, LSD, my problem child.

  In the early 1960's, when I had satisfied myself that the effectiveness of TMA-2 was intensified by the structural change that gave MEM (but not EMM or MME), it seemed a logical question to ask: was this because of the nature of that group in the magical 4-position? This 4-position substituted drug might have maintained its activity specifically because of the fragile nature of these groups, which would allow their easy removal by the body (or within the body) and the formation of some metabolic product that just happened to be much more potent. The human body has excellent facilities for changing molecules, and it usually changes them to make something less threatening. But in this case the change just might have achieved some upgrading of potency.

  Or maybe that group at the 4-position was not easily gotten rid of. Then one could argue that an indestructible molecule got settled in the receptor site, and simply stayed there. The new compound is fully as potent as the old one, because it gets in there and cannot be removed metabolically for some time. The easiest way of answering this question was to construct a molecule with a group at that position which could not be easily displaced or changed.

  I said to myself, let's replace the 4-methoxy group (of TMA-2) (or the 4-ethoxy group of MEM) with a methyl group. We will call it DOM (for TMA-2 without an oxygen atom but with a methyl group, desoxymethyl). The methyl group (at the 4-position) cannot be removed easily by any of the usual metabolic procedures. Thus, if this compound (DOM) is of reduced activity, the metabolic removal of some 4-position group seems a reasonable explanation of biological activity. And if the compound (DOM) maintains activity, it would argue that TMA-2 and MEM

  are intrinsically active, and something in the 4-position is instrumental to the expression of central action. In simple terms, the 4-methoxy group is fragile, and the 4-methyl group is solid. If the active 4-methoxy compound (TMA-2) becomes inactive with a 4-methyl group (if DOM is of decreased potency) then fragility (metabolic change) is needed for activity and the intrinsically active form is to be found somewhere down the metabolic pathway. If, on the other hand, the activity is maintained with the 4-methyl group (if DOM is fully potent) then the primary agents (TMA-2 or DOM) are the responsible factors, and metabolism only serves to inactivate these drugs.

  The very first step toward this noble end-product DOM was actually taken by my son, Theo, who was with me late one evening at Dole, on June 22, 1963, to be exact. Having him with me was probably against all the rules, but he was in a period when he wanted to become a chemist, so at about 9:00 p.m., with my blessings, he dumped 100 grams of 2,5-dimethoxy-toluene into a mixture of 225 grams of N-methyl-formanilide and 255 grams of phosphorus oxychloride, thus launching the synthesis of a precursor for what was eventually to be DOM.

  He ended up in the early hours of the morning with some 54.9 grams of an aromatic aldehyde that did the job. We had our precursor.

  (Theo's interests in chemistry have largely flagged and he has found his metier in marine biology and superb poetry, with a garden full of lovingly tended chrysanthemums and dahlias affording him hours of peaceful contact with the earth and his own inner being.) I completed the nitrostyrene synthesis on July 7th, and finally got back to this project on the 30th of November, to finish the reduction to the final amine. The next day, at 3:22 p.m., I tried 200 micrograms of the white solid and, as there was no effect whatsoever, I let the whole matter drift over the holidays. On January 4th of the new year, I rather heroically upped the dosage to a milligram and, to my total surprise, found activity there. This was the first time ever that a phenethylamine had been observed to be centrally active at such a miniscule dose.

  Although there was no response by the end of the first hour, I noted a dryness of the mouth at around the third hour, and my eyes were extremely dilated. I had an eerie over-all feeling that lasted for a couple of additional hours, but eating seemed to clear it up, for the most part. By the seventh hour, everything was repaired, back to normal, and I decided to doubt the validity of any of it.

  I noted some residual muscular pains which I readily ascribed to having hiked six miles the previous day. It was during this period of my employment at Dole that I established patterns of hiking to work, and then driving - each on alternate days. I would meet with other co-workers who were also outdoor types along the way, and, unbeknownst to them, I would often have a new level of a new compound on board. We would pick up Al at the drainage ditch. Bob at the edge of the Bainbridge Ranch, and all of us hiked along the canal until we were opposite the back parking lots of Dole. We would cut in opposite the electron accelerator and head for fresh coffee, they with wet feet and incipient muscle tiredness, I with wet feet, incipient muscle tiredness and a possible plus-one or plus-two altered space.

  Five days later, I tried a slightly increased level of DOM and recorded in my notes what was probably my first plus-2 experience on a material that was this much a stranger to mescaline.

  At about the 1-1 /4 hour point, I was talking to a friend in his office when I became aware of a warm flushing and tingling sensation in my genitals, which occasionally was a prelude to nausea. My mouth was dry. The nausea did not develop. At the 2-hour point, my teeth were what I call "rubby," which means that I'm suddenly aware of them and they have the feel of being squeaky clean. I was aware of some pressure in the ears.

  Two points deserve comment here. One is that with every new drug, at the low levels where there is clearly some action, but the nature of that action cannot yet be defined, one reads every unknown possible complication into one's responses, often recording a syndrome that can never be repeated. The second point is that, at the time, I was still most naive in the area of drug effects, and just a bit frightened, so I'm sure that I often mentally promoted signs and symptoms that were not valid.

  Between the third and fourth hour, I wandered out to the little greenhouse I had put in near the parking lot, where I had planted some Salvia divinorum, and relaxed in the pleasure of watching things grow. I knew that at higher dosages plants would creep and crawl, but now they were just visibly growing. Between the seventh and tenth hour, I recovered a good baseline and brought my notes to a close, before heading home.

  Through the year 1964, DOM was being evaluated by several of my allies, in the dosage range of 2 to 4 milligrams. I was still dedicated to marginal threshold dosage evaluations, unwilling to dip into the spring deeply. I admire, to this day, the brave souls who worked with me to explore the nature of this material. My friend, Terry, evaluated 2.3 milligrams. and reported an extraordinary mood elevation, with no indication of any nausea whatsoever. In the third hour, he found a pronounced enhancement of odors and of emotional interactions, with a richness of empathy. At the eighth hour there was an unmistakable decline, and a 3/ 4 grain of seconal was needed for sleep at the tenth hour. He did a later experiment with 3.8 milligrams and reported that it showed its maximum effect at the fifth hour, with a peaking from there to the eighth hour, and a gradual decline on into the 12th hour. This was the first clear portrayal of the very long time course that this drug shows.

  The first full "psychedelic" experience of DOM was reported by another friend. Mark, at 4.1

  milligrams. For him, the effects were noted at about half an hour, and between 1-1/2 and 3

  hours there was a matter-of-fact but impressive recounting of visual and interpretative effects similar to those of mescaline. It wasn't until his fifth hour that these really broke through, and his notes are replete with superlatives. For him, there were colors and textures without precedent, as he had no past experience with color effects from mescaline.

  It was many years later, in 1967, that some unknown enterprising chemist introduced DOM

  onto the street, where it was called STP and, unfortunately, it was distributed in doses of up to 20 milligrams. When you consider that the active level, a plus three effect, is clos
er to 5

  milligrams, it is not surprising that the emergency wards of numerous hospitals began seeing young people in states of confusion and panic. They had taken the new drug and, when nothing seemed to happen within the first hour, some of them believed they had taken too low a dose, and took another pill. The hippies and street people were used to drugs like LSD, which come on relatively quickly and are completely developed by one hour. The person responsible for this debacle must have realized his error, because within a relatively short period of time, he had put out new tablets which were only 10 milligrams each. This was still a whopping amount.

  While I was in medical school, I heard the rumors and the reports about something called STP

  and wondered, along with everyone else, what it was. Initially it was thought to be some scopolamine-like drug, but then its nature became more evident. In time I learned that it was, indeed, DOM. Maybe it had became known from a seminar I gave at Johns Hopkins, months earlier, in Baltimore. Maybe the patents had been read and duplicated. Maybe someone had followed the same quite reasonable line of reasoning that I had. But, my challenge to the meaning of the 4-position was now public property, and there was no remaining question as to mechanistic logic. The unchangeable group at the 4-position gave a compound not just of similar potency, but of greatly enhanced potency. Clearly, that 4-position needs to remain untouched, metabolically, (for a while), if a compound is to be active.

  In going through my files recently, I discovered a handwritten note that had come to me not long after the first trials with this material. It was short and impressive. I have no idea from whom it came, so no answer could ever be sent It implied an experience that had several faces:

  "If on this page I shall have expressed it to you, then it is true that DOM has the glory and the doom sealed up in it. All that's needed to unseal it is to surround it with a warm living human for a few hours. For that human, for those hours, all the dark things are made clear."