by Power, Mike
And here is the third molecule in our triptych, mescaline:
Mescaline
The same basic phenethylamine skeleton is present in the second two molecules, but we can see that there are a number of other molecular groups attached to it. (These diagrams are, incidentally, 2D renderings of 3D objects.) The mescaline molecule fits into the dopamine receptors in the brain, and, in some way yet to be understood, affects our perception of reality in radical and unusual ways.
Shulgin took the mescaline molecule, and swapped the hydrogen molecules attached to each of the carbons on the benzene ring for other chemicals. He added sulphur molecules, or cleaved off an atom or two of oxygen here, spliced in an iodine or a bromine there, exploring the possibilities of chemistry.
Shulgin’s intense, rigorously academic study gave him pointers towards the likely effect and dosages of most of the new drugs he was inventing. But sometimes he simply added a chemical at various different positions on the ring and tested the drugs on himself to see what happened. He carried out the same process with both the mescaline molecule and with variants on the tryptamine skeleton, the parent structure for magic mushroom-like drugs.
Where mescaline most closely resembles the phenethylamine and dopamine neurotransmitters, tryptamine resembles serotonin. Drugs containing tryptamine work by entering serotonin receptor sites in the brain, and by some sub-atomic magic, triggering a release of it, which affects mood, social behaviour and impulsiveness. It limits other neural activities and changes our perception of reality in the process. How these substances achieve this in neurological terms is hotly debated, but the latest research suggests that when flooded with serotonin the mind dampens down brain activity, rather than increasing it, as had long been thought. (These descriptions deliberately and necessarily simplify the interaction between drugs and the brain, since each category of drugs actually acts on both systems at once, and each system is far too complicated for any non-scientist to describe – or read about.)
As the social taboos and moral panics around psychedelics started to build, Dow found itself the uneasy holder of patents for powerful psychedelics such as DOM – a designer drug created by Shulgin and popularized following the outlawing of LSD. This potent drug flooded the streets of Haight-Ashbury in 1967 and is said to have caused many traumatic episodes as tablets containing guaranteed overdoses of the chemical circulated in their thousands. Syd Barrett of Pink Floyd is said to have been profoundly affected by the drug in the years preceding his nervous breakdown and withdrawal from society.4
Shulgin left Dow in 1965 and set up his home laboratory in Lafayette, where he continued engineering new drugs from the basic mescaline phenethylamine structure. In the process he revolutionized our knowledge of biopharmacology, and set in motion, unwittingly, the global shift in drug use that has been witnessed since the mid-to-late 1980s. He worked for the DEA as an expert witness, supplying them with reference samples for use in criminal trials, and was otherwise left to his own creative devices.
Shulgin blurred the lines between the epiphanies of art and the harder edges of science. His career during this period can be seen, by those who are sympathetic, as a reinvention of the American pioneer spirit. He pushed the boundaries of his own mind, searching for a manifest destiny of his own, for an American expansionism anyone could believe in – but with no harm to others ever intended, and no presumption of ownership ever made. With his unruly beard, ready grin, colourful baggy shirts and loping gait, the endlessly punning chemist worked in his ramshackle garden shed laboratory, surrounded by thickets of glassware and dangling, vine-like tubing, the air thick with volatile gases and the thunderous chords of his beloved Rachmaninov.
Eventually, sensing a change in the attitude of the DEA towards his work, Shulgin published his entire body of knowledge in two seminal works of psychedelic chemistry: PIHKAL (Phenethylamines I Have Known and Loved): A Chemical Love Story, in 1990 and, seven years later, TIHKAL (Tryptamines I Have Known and Loved), which covered the other major class of psychedelics. Psychedelic pioneer Timothy Leary has compared PIHKAL to Charles Darwin’s On the Origin of Species,5 and, while most of Leary’s grandiloquence can be safely disregarded, it’s arguable that on this he was right. The DEA did not share that view, and they raided Shulgin’s lab in 1994, accusing him of possession of compounds he was unauthorized to own. Shulgin was found to be in possession of various samples of drugs people had sent him, anonymously, to test, which was an infraction of his DEA licence.
PIHKAL reveals in practical detail the chemical synthesis and human dosage of hundreds of psychoactive substances, each of which are in the phenethylamine class. At the time of its release, many of the precursor chemicals, that is, the ingredients required to produce them, were not banned and were available without excessive governmental interference.
While it’s in no way comparable in terms of complexity and difficulty, drug chemistry is, to all intents and purposes, much like baking. Both aim to take one type of matter and use the physical forces of heat and chemical reactions to transform it. The cook and the chemist both need ingredients, techniques, equipment and expertise. Where a cook uses flour and fat and heat, a chemist such as Shulgin might use an essential oil, such as oil of parsley, or safrole, as a precursor, its similarity to pre-existing drug structures, such as amphetamine, making fewer chemical reactions necessary.
Indeed, in PIHKAL Shulgin identified ten amphetamines that were closely linked to essential oils and he deliberately chose precursors that were, back then, available without a great deal of trouble. ‘What are these relationships between the essential oils and the amphetamines?’ he wrote. ‘In a word, there are some ten essential oils that have a three-carbon chain, and each lacks only a molecule of ammonia to become an amphetamine.’6
Since their publication PIHKAL and TIHKAL have served as guidebooks to the new chemical terrain, their pages revealing in detail the doses of new and unknown drugs. But these are not orthodox academic manuals. The books mix chemistry and synthesis guides with wry asides, trip reports, and the story of the love affair between Shulgin and his wife, Ann, a counsellor and psychotherapist who has used many of her husband’s drugs in her practice, with, she says, great success. PIHKAL also contains an extended riff on the reasons behind Shulgin’s quest for psychedelic experiences. These drugs were for research, for exploration, and for the pursuit of spiritual and psychological insights, he writes:
I am completely convinced that there is a wealth of information built into us, with miles of intuitive knowledge tucked away in the genetic material of every one of our cells. Something akin to a library containing uncountable reference volumes, but without any obvious route of entry. And, without some means of access, there is no way to even begin to guess at the extent and quality of what is there. The psychedelic drugs allow exploration of this interior world, and insights into its nature.
Shulgin also reflects upon the unprecedented nature of the attacks made by governments upon those whom he sees as seekers of spiritual truths:
Our generation is the first, ever, to have made the search for self-awareness a crime, if it is done with the use of plants or chemical compounds as the means of opening the psychic doors. But the urge to become aware is always present, and it increases in intensity as one grows older […] This is the search that has been a part of human life from the very first moments of consciousness. The knowledge of his own mortality, knowledge which places him apart from his fellow animals, is what gives Man the right, the license, to explore the nature of his own soul and spirit, to discover what he can about the components of the human psyche.7
Shulgin argues passionately for free speech and the rights of the individual; there is no one less un-American than this chemist savant, yet he remains an outcast even today, in his old age. He asks: ‘One of the major strengths of our country has been in its traditional respect for the individual … How is it, then, that the leaders of our society have seen fit to try to eliminate this one very important
means of learning and self-discovery …?’8
Luckily for science, Shulgin and his friends decided that their minds and bodies were their own dominion, and self-experimented with the new compounds he created. Shulgin would gradually increase his doses by minute increments until the desired effects were felt. He would report on the drugs’ efficacy and their impact on what he called ‘the erotic’ – he and his wife agreed that any drug that precluded their lovemaking was undesirable – and his research group would offer their findings on the drugs’ effects on music appreciation and their artistic sensibilities in genteel and discreet prose. Shulgin even pioneered the concept of the ‘museum dose’ – a quantity of a drug that he deemed appropriate for trips to interesting exhibitions. He and his group would measure each of the experiences according to an agreed scale and write up their impressions, from a ‘plus one’ up to a ‘plus four’. The ‘plus four’, he wrote in PIHKAL, was a ‘a rare and precious transcendental state, which has been called a “peak experience”, a “religious experience”, “divine transformation” a “state of Samadhi” and many other names in other cultures.’9
Each entry begins with a densely complex synthesis for each drug. A typical entry, for TMA, a mescaline derivative, reads thus:
To a solution of 39.2 g 3,4,5-trimethoxybenzaldehyde in 30 mL warm EtOH there was added 15.7 g nitroethane followed by 1.5 mL n-butylamine. The reaction mixture was allowed to stand at 40°C for 7 days. With cooling and scratching, fine yellow needles were obtained which, after removal by filtration and air drying, weighed 48 g. Recrystallization from EtOH gave 2-nitro-1-(3,4,5-trimethoxyphenyl) propene as yellow crystals with a mp of 94–95°C.10
The remaining 600 words of chemical nomenclature and technique would make even less sense to anyone except highly trained organic chemists. But then the register shifts dramatically as users describe their experiences:
[With 225 mg of TMA] There was quite a bit of nausea in the first hour. Then I found myself becoming emotionally quite volatile, sometimes gentle and peaceful, sometimes irritable and pugnacious. It was a day to be connected in one way or another with music. I was reading Bernstein’s Joy of Music and every phrase was audible to me. On the radio, Rachmaninov’s Second Piano Concerto put me in an eyes-closed foetal position and I was totally involved with the structure of the music. I was suspended, inverted, held by fine filigreed strands of the music which had been woven from the arpeggios and knotted with the chords. The commercials that followed were irritating, and the next piece, Slaughter on Fifth Avenue, made me quite violent. I was told that I had a, ‘Don’t cross me if you know what is good for you’ look to me. I easily crushed a rose, although it had been a thing of beauty.
Of the hundreds of phenethylamines he explored or invented Shulgin identifed six as being particularly useful for the exploration of inner space, and for understanding reality in new and extraordinary ways. These were mescaline, DOM, 2C-B, 2C-E, 2C-T-2, 2C-T-7. The differences between each drug can be measured, prosaically, by descriptions of their dose, their duration and their chemistry. More poetically, members of his test group would discuss them as wine buffs might discuss a fine Pétrus, appreciating the finer points of their effects. Some approached it from a spiritual perspective, and ranked the drugs on the insights the compounds gave them into their own natures.
The phenethylamine that would catapult Shulgin’s work from academic and even psychedelic obscurity into the mainstream, though, would be MDMA, or Ecstasy. MDMA does not exist anywhere on earth naturally, but its synthesis can be arrived at in a couple of days by a moderately competent chemist, given access to the right materials and equipment. There are a number of different routes to the production of the drug, including isosafrole, MDP-2-P, piperonal and beta-nitroisosafrole. The easiest synthesis for MDMA, though, is from an essential oil, safrole, that acts as a natural pesticide for the plants that produce it. With a sickly-sweet synthetic smell somewhere between marzipan and aniseed, the oil is used legitimately in the perfume and flavourings trades; but buying it in any quantity will ensure your almost immediate presence on a police watch list, as it is a well-known and internationally banned precursor to MDMA.
In around 1965, Shulgin synthesized the drug using safrole as a precursor, and in 1967 he started to work with the new drug himself. Entry 109 in PIHKAL would prove to be the most revolutionary of the hundreds it contained. PIHKAL does not attribute authorship to its substance reports, and Shulgin himself never (publicly) rhapsodized about the power of MDMA, comparing it instead to a low-calorie martini. One of his test group, however, felt somewhat differently:
(with 120 mg) I feel absolutely clean inside, and there is nothing but pure euphoria. I have never felt so great, or believed this to be possible. The cleanliness, clarity, and marvellous feeling of solid inner strength continued throughout the rest of the day, and evening, and through the next day. I am overcome by the profundity of the experience …
(with 120 mg) The woodpile is so beautiful, about all the joy and beauty that I can stand. I am afraid to turn around and face the mountains, for fear they will overpower me. But I did look, and I am astounded. Everyone must get to experience a profound state like this. I feel totally peaceful. I have lived all my life to get here, and I feel I have come home. I am complete.11
What exactly did these molecules do to the human mind? What is the chemical process by which a certain arrangement of atoms can make a user experience bliss? How can a chemical make an instant seem eternal, or transform the banal into the transcendent, or turn a blinding spotlight on to ineffable universal mysteries, for a brief, possibly delusional moment?
Drugs hijack our neural circuitry and change the way we feel, how we see and hear and interpret the world, and in the case of some psychedelics, how we see ourselves. As we saw above, they work in this way, in the most basic terms, because their molecular structures closely resemble naturally occurring chemicals, or neurotransmitters, that are generated by our brains to regulate mood, muscle action, appetite and dozens of other important physical processes. Drugs act as chemical ‘keys’ that somehow fit into the transmitters’ ‘locks’ in our brains. These molecules circulate, and are received back into the site that transmitted them, much like hot water in a radiator and boiler system.
Prozac, the antidepressant, works on the brain’s levels of serotonin, the chemical that is triggered when we experience stimulus that results in joy, but the effects of this and the dozens of other pharmaceuticals in its class are gradual. They work more on inhibiting the synapses’ reuptake of naturally circulating serotonin, rather than triggering unusually large quantities of it. When we take MDMA, serotonin floods the brain, and our synapses’ regular pattern of release and reuptake are dramatically changed by the presence of the drug.
There are also serotonin receptors in the heart and the stomach, which goes some way to explaining the concept of gut instinct, or feeling lovesick when missing a partner, the sensation of butterflies when meeting a loved one after an absence, or the real and physical trauma of a truly broken heart.
MDMA also produces a flood of dopamine, the neurotransmitter pumped around our brains when we are excited, or sexually aroused, or seeking or receiving rewards. And finally it also leads to the release of norephrenine, also known as noradrenaline, a neurotransmitter released when we are frightened or angry or edgy, which increases respiration and heart rate.
The magical ratio of serotonin-dopamine-norephrenine release and reuptake prompted by the presence of MDMA in the human brain is not produced by any other substance. Other recreational drugs come close, but the charged, empathetic, transcendent, peak-MDMA experience has yet to be matched by any designer drug. It’s called Ecstasy for a reason.
This fascinating, mysterious collision between the physical and the intangible, between the flesh and photon, reframes all human consciousness as a chemical reaction. That’s the science of it, but human emotion and the mystical experiences some drugs afford users cannot be so neatly quantified.
MDMA was used initially in the 1970s by psychotherapists in the USA excited by the drug’s therapeutic potential. One such was Leo Zeff, who had been introduced to the drug by Shulgin in 1977. The California-born practitioner was so thunderstruck after his first experience that he cancelled his retirement and travelled the country dosing thousands of willing users with the drug, whose extraordinary qualities of personal boundary dissolution he believed would help therapists to discover the root of a sufferer’s problems. Zeff claimed that a single MDMA-assisted therapy session could accomplish as much as six or more months of traditional therapy. Therapists say the drug first helps patients to open up and discuss their problems honestly, and then enables them to engage in objective analysis without self-judgement, and finally allows them to generate solutions.
Shulgin hated the term Ecstasy, preferring the stark chemical nomenclature of MDMA. The name Ecstasy was popularized by an ex-priest-turned-MDMA-propagandist, Michael Clegg, whose E-triggered epiphany was so utterly damascene when it came that he started to press the pills himself and give them away for free. But this was the yuppie era, and by 1984 the ‘Texas group’ – a loose conglomeration of dealers – was selling 500,000 pills a month in that state alone. When he was warned that if he carried on selling it so openly the drug would be banned, Clegg is said to have responded: ‘Yes, and then I’m going to get very rich.’12
In the mid-1980s, designer Phillipe Starck’s eponymous Dallas, Texas, nightclub was a hotbed of early public, hedonistic MDMA use, a tactile bacchanal with unisex bathrooms, playing kitschy synthpop and frequented by patrons with prominent cheekbones and heavily moussed hair. The pursed lips and swinging hips, the primped pomp and sexual display, the high-sheen finish and conspicuous consumption could not have been more removed from a therapist’s sofa: it was an orgiastic, consumerist 1980s riot with guest star appearances by imperious Jamaican diva Grace Jones. Fittingly, a CD compilation of the music played at the Starck club sold in 2007 for over US$14,000 on eBay.
