Pihkal

by Alexander Shulgin

  CHAPTER 5. BLACKWOOD ARSENAL

  It was somewhere around 1960 that I met a brilliant neurologist. Harry Bush, who had become totally fascinated by lichens, and had invested much effort in their identification and characterization. I learned much from him about the symbiosis between algae and fungi, and I learned that some of the chemicals contained in lichens can easily be brought to react with certain essential oils from natural sources, to make a synthetic tetra-hydrocannabinol or THC

  (the active component of marijuana). There was considerable satisfaction for me, and more than a little humor, in the knowledge that, by wandering around a camp ground and mixing an extract of the colored scabs flicked off a big rock with some orange peels from the nearest garbage can, in the presence of phosphorus oxychloride (you would have to bring that yourself), and finally putting the cleaned-up product on parsley and rolling it into a kind of cigarette, you could produce a potentially psychoactive smoke.

  All this led me to a lot of literature searching and quite a bit of chemical diddling (I was still working at Dole), and it was through this that I was introduced to the wonderful world of plant products. I was already well aware of the strongly alkaline compounds known as the alkaloids.

  These were the nitrogen-containing products most often responsible for the biological activity of the plant. Drugs such as nicotine, strychnine and quinine are famous, and even the psychedelic area is well represented by indoles such as DMT, 5-methoxy-DMT, psilocin, psilocybin, and our archetypal phenethylamine, mescaline. But I began to appreciate other families, usually neutral compounds that were inactive, but which smelled nice and were potential starting materials for chemical synthesis. There were terpenes which are the sharp smells of conifers and camphor. And there are the magnificent essential oils that are the smells of the spice cabinet; the oils of nutmeg, clove, parsley, dill, and apiole. And on and on. This little-studied collection of chemicals proved to be an unending source of ideas in the psychedelic area.

  Then, three things occurred in rapid sequence. First (and of interest mostly to people who fool around with chemistry), I sharpened up the lichen/orange peel strategy and found that the condensation product from olivetol (which could actually be isolated from certain lichens that I collected just north of Ottawa) and pulegone (a terpene from pennyroyal, a peppermint-like plant that can be found growing profusely near Alamogordo in New Mexico), produced a sizable quantity of the marijuana-like material resembling THC. The groundwork for this chemistry was laid by Roger Adams, at the University of Illinois, before World War II. He, and A. R. Todd at the University of Manchester, in England, had a vigorous rivalry being waged in the chemical literature as to who could get closer to the chemical duplication and animal demonstration of the active components of marijuana. The culmination of Adam's work was the preparation of a mixture of synthetic products that proved, in his dog model, to be many times more potent than the natural drug. This has been called, "Adam's nine-carbon compound," since it has, not surprisingly, a nine-carbon unit in the terpene half of the molecule. This point is mentioned here only because it will reappear a little later in this account. An interesting sidelight is the fact that the precise structure of THC was still unknown at this time (some twenty years after the conclusion of Adam's work).

  Secondly, it occurred to me that Mother Nature, which thoroughly loves alkaloids, kind of blew it in letting the Cannabis plant make a psychoactive compound devoid of nitrogen (the necessary component of an alkaloid). What would THC look like pharmacologically if it were a phenethylamine? I said to myself, "Let's make it!" So I hied myself off to the library to begin unraveling some possible paths to the synthesis.

  And thirdly, a group of researchers (men with cautious faces, wearing proper suits and ties) from the Blackwood Arsenal, the chemical and biological warfare branch of the U. S. military, visited Dole to meet with some of the company's scientists in a brain-storming session. The visitors had some synthetic problems which could only be stated in the most general of terms, as they involved compounds that could not be explicitly described, having been assigned some classified information status, and some of us who were present did not have any kind of security clearance.

  Anyway, the sum total of their query was neatly organized on a slide which showed a reaction scheme down the left-hand side of the screen, leading to the penultimate compound A, and another scheme down the right-hand side of the screen, leading to the penultimate compound B. The product (from A reacting with B) was not on the screen at all, since it was considered secret. Their questions centered on the two displayed sequences. Could any of us come up with some jazzy ideas for easier or better syntheses of either A or B? Ideas were bounced around for a while, then I got into one of my more manic moods and grabbed some chalk. I said, in essence, that although none of our visitors were prepared to say just why it was they wanted efficient ways of making A and B, it seemed an interesting coincidence that the simple coupling of A and (using the phosphorus oxychloride procedure that worked so well with the lichens and citrus fruit) would surely produce "Adam's nine-carbon compound," which was (in case they were not aware of it) some five hundred and twelve times more potent in the dog motor ataxia test than the synthetic THC analog which was being used at the time as a reference standard.

  Silence.

  I bubbled on - having written the structure of this obviously classified compound on the blackboard - that if one were to conduct the synthesis as had been suggested on the slide in any way other than the explicit procedure described by Adams, one would end up with a mixture of products which would (due to the fact that there are several optically active centers involved) produce a mixture containing a total of eight isomers. And if any deviation were to be made from the original synthesis, the ratio of these isomers just might be radically changed, with a resulting biological activity that might be radically different from that observed by Adams (the 512 times potency job).

  The silence was thicker.

  More manic yet, I went on to say that, to be completely scientific about it all, these eight compounds should each be explicitly synthesized as individuals, and should each be separately assayed as unique entities. And, as a throw-away, I mentioned that if they really wanted to remedy Nature's sloppiness, they should consider synthesizing this unnameable target compound with a nitrogen atom in it, so as to emulate an alkaloid. That, I added in conclusion, might be a really super-potent phenethylamine!

  The silence persisted for a few moments, and when the talking eventually resumed, it wended its way into other areas, and eventually the visitors returned to Maryland.

  The entire incident was forgotten with the trauma that accompanied the unexpected and untimely death of my mother, while she and my father were at their summer cabin at Lake Tahoe, high in the Sierra Nevadas. It was a difficult transition for Helen and me, but especially so for Theo, who had developed a close and intimate relationship with his grandmother. As to my father, I noted signs of a subtle deterioration which we all saw as progressively robbing him of both spirit and motivation.

  Finally, I said Enough! Let's all go on some sort of short get-away, to give ourselves a chance to repair. Where should we go? It didn't matter, I said; I'll take care of it. So my father put a clean pair of socks and a change of underwear into a satchel, and all four of us set out for San Francisco, supposedly headed for San Diego. In actuality, unbeknownst to my father, I had arranged to have the house sealed off for a long absence, and I'd gotten tickets on the P & 0

  ship Chusan for a trip, not just to San Diego, but past it to Panama, then to Trinidad, Barbados, the Canary Islands, England, and on to France, where we would stay for a year. The true unrest cure, as in the wonderful short story by H. H. Munro.

  (The plan worked. My father had to buy a whole new wardrobe; he re-established contacts with Russian-speaking friends whom he hadn't seen for a quarter of a century; he completely severed himself from his grief-obligations, rediscovered his identity and his energy, and he later remar
ried, opened a restaurant, and lived another fifteen years. But that, as they say, is another story.)

  Back to the beginning of our trip. We were about a day out of Port-au-Prince when the first bird from the Blackwood Arsenal nest came home to roost. It was about five in the morning, and Helen and I were sound asleep in our dark inside stateroom on D-deck, when there was a rapping at the door. I got up and uttered a very bad word; I had forgotten I was in the upper bunk, so my step down to the floor was a four-foot jolt. I opened the door to meet, face to face for the first time, Mr. Munoz of the radio room.

  "I have a radio communication from RCA International for you," he said, handing it to me. I found a flashlight and read it. Some 500 words from a Dr. Frederick Pearsman at A.R.L.

  Company in Cambridge, Mass., saying - nay, demanding - that I call him from Trinidad collect when I arrived (we were due there the next day). I had no sooner gotten back to sleep, than there was another knock on the door. Mr. Munoz, again. He said that he had just received another radio communication for me, this time via ITT or something, but not to bother reading it as it was, word for word, identical to the first one. "Okay, okay," I muttered, "I've got it: I'm supposed to make a call from Trinidad."

  Morning came, and with it came Trinidad, along with heat and humidity. I spent almost an hour in a telephone booth, talking to Fred Pearsman at A.R.L.

  Dr. Pearsman said something like this, "We have been asked to submit a contract proposal, by a group which we can't really identify, to synthesize a nitrogen-containing phenethylamine analog of THC. You will be arriving in London at such and such a time on such and such a day (he was correct to the minute) and we want you to please send us a complete synthetic procedure at that time by airmail special delivery the very minute you arrive. It will get to us here just in time for our submission."

  "But," I protested, "I'm aboard a luxury liner, and the most up-to-date reference book in its library is an 1894 edition of Roget's Thesaurus!"

  "Then write it out from memory," said he, and that was that. I cannot begin to describe what forty minutes in a Trinidad telephone booth at 90% humidity and 92 degrees temperature can do to one's rational defenses.

  So, for the rest of the way across the Atlantic Ocean, I reviewed, with what modest photographic recall I could muster, the appropriate texts of Beilstein and Chemical Abstracts, and put together a chemical flow-sheet and proposal for the phenethylamine analogues of THC. It was mailed from London and got to A.R.L. Company apparently in time for the contract proposal to be awarded to them. It must have been somewhat successful in showing CNS

  activity, since Dr. Pearsman left A.R.L. and became the founder of a consulting group in Boston that promoted nitrogen-containing THC analogs to industry, apparently with some success.

  I got my name on a patent that was subsequently issued to the Simpson Winter Corporation, and for which I received a token dollar; that is the way things are done when one works for industry. I never found out what the connection was between Blackwood Arsenal, A.R.L. and Simpson Winter. I also never met the man I privately dubbed "Frantic Freddy," although I did run into people at several scientific meetings in following years who knew him. His company has continued to grow, and today it is pursuing a large number of research projects in the area of pharmaceuticals. Their work occasionally touches the THC molecule with imaginative variations, but as to the putting of a nitrogen atom in there, not much more has been done. I did put out a few more materials with that THC-nitrogen combination from my own lab sometime later, which earned me a trip to Sweden. But I found nothing of psychedelic interest.

  Maybe nature wasn't being sloppy by leaving it out. I suspect she knew it wasn't worth it and was simply saving her energies.

  The rest of the ocean passage to Europe (the time not spent in writing the rough draft of the government grant) was spent in developing the art of playing Ping-Pong on a rolling ship, and learning about the initiation rites of obscure African tribes from our radioman Mr. Munoz, who evolved into an interesting and constant pre-dinner cocktail companion.

  I have lost all touch with Mr. Munoz; I do not know if he is even alive today. The P & 0 Lines certainly did not survive.

  CHAPTER 6. MMDA

  I had a number of projects that I wished to pursue in France. I wanted to learn to speak the language, I wanted to break my father loose from his grief over the death of my mother, and especially, I wanted to put a methylenedioxy group in place of two of the methoxy groups in TMA. The three methoxy groups of mescaline and of TMA have oxygen atoms that are sticking out from the benzene ring all isolated like islands. They are not interconnected. If two adjacent ones were to get a bridge between them, be tied together, then a very subtle change in the geometry of the molecule would result. The name of the bridged analogue would be MMDA.

  All of this grew out of nutmeg. At Dole, having seen the effectiveness of TMA, I put myself to searching in catalogs, in books, on shelves, in plants, for anything that resembled it and which thus might indicate where I should go next. I discovered a few mentions in the literature of an intriguing compound called elemicin. It was an essential oil (a new term to me) which was one of a large class of compounds responsible for the flavors (the essences) of many of our food stuffs. So it looked as if plants were the direction to go.

  Elemicin looked (in the structural sense) almost identical to TMA. Through the magic of blackboard and chalk, I could add a molecule of ammonia to a molecule of elemicin and get a molecule of TMA. And if it could be done on a blackboard, maybe it could be done in the liver.

  Was there any suggestion or report, I wondered, anywhere at all, suggesting that elemicin had psychoactive properties?

  Off I went to an exciting few days in the published literature, during which I learned a great amount about the intriguing world of essential oils. They were everywhere, wonderful structures to be found in spices and related plants, with names that often reflected their origins: elemicin, api-ole, dill-apiole, safrole, eugenol, anol, croweasin, myristicin, asarone, and on and on. A wealth of obscure, unexpectedly magical chemistry completely ripe for exploration and exploitation.

  Well/ although I could find no specific mention of any psychopharmacology of elemicin, it is one of the major components of nutmeg, and there was a vast anecdotal literature concerning nutmeg. It had been used for everything from inducing abortions and reinstating missed menstrual periods, to attempted suicide and curing baldness. And bingo! It also had a wide reputation as an intoxicant.

  Apparently, nutmeg has been used as a "kitchen narcotic," in prisons, and a scatter of medical reports have appeared describing several patterns of drunkenness or psychic disorder. It contains elemicin, which is structurally almost identical to TMA. What else might be in nutmeg that could cause or contribute to its folklore reputation? I pursued the answer by the straightforward process of buying ten pounds of high quality Oil of Nutmeg, and fractionally distilling it through a super-efficient still into some three score fractions. What a treasure of compounds! In fact, several of them had never been observed in this plant extract before.

  A major component present was myristicin, a known close relative of elemicin. If one could stir simple household ammonia into elemicin to convert it to the strange and challenging psychedelic TMA (at least in theory), then a similar stirring of ammonia into myristicin should give rise to the unknown base, 3-methoxy-4,5-methylenedioxyamphetamine, or MMDA.

  In principle, I thought the synthesis of MMDA should be simple and straightforward. Just take the correct starting aldehyde, myristicinaldehyde, and follow the standard procedures. Which is something like the famous recipe for hippopotamus soup: take a mature hippopotamus and follow the standard procedures. There is no obvious way of getting hold of a hippo, and I was going to discover that there was a similar problem in the getting of myristicinaldehyde. It was simply not available, and extraordinarily difficult to make. But I was totally determined to make MMDA and discover whether it was active and, if so, just what the actio
n would be.

  Arrival for a year's stay in France can be somewhat traumatic even if there are reservations and arrangements and places to go and people to contact. In this case, there were practically no plans whatsoever. We (my wife Helen, my son Theo, and my grieving father) found our way to London to pick up a new Volkswagon (that much had been arranged), and we piled all our belongings on top of it and headed for the English Channel. Across it we went, on the night ferry, and roared south to Paris the following day.

  So there we were, with no place to go and no person to contact. We found the American Express office up near the Opera, and there were no messages for us. But, then, we hadn't really expected any. Clearly, we had to spend a year in some location, but the most immediate problem was where to spend a night while we searched for the place to spend a year.

  It was already late afternoon. I vaguely remembered that there were some neat hotels somewhere around St. Germain des Pres, and we found that the Hotel aux Deux Continents had a room on the fifth floor. On the top of the Volkswagen we had a giant tea case and three suitcases, which carried all of our needs for the year. I managed to convey to the manager of the hotel that my father had an extremely weak heart (necessity is the mother of many little fibs) and that his walking up to the fifth floor and down again might seriously threaten him.

  And certainly his carrying baggage to the fifth floor would be even riskier. The manager then just happened to discover a room on the ground floor which, by good fortune, had a large window which opened out onto the street, so we passed in all the luggage from the sidewalk through it, and settled in for a while until we could find an apartment.

  The complete absence of available downtown Paris rentals soon became apparent, so we finally located ourselves in the suburb of Meudon. I immediately set out on the quest for myristicinaldehyde and a laboratory where I might convert it to MMDA. What I found was that the French have a way of regarding academic positions and related research projects in a framework that is completely alien to an American. One cannot simply go into a university and say, "I am me, and I would like to meet you." All doors are locked and no one responds to telephone calls. One must go through channels.