Better living through chemistry

It was an extraordinary gathering of individuals that came together at Berkeley in California. There were hippies, heroes of 1960s counterculture, neurobiologists, artists and Bradley Horowitz, a vice-president of Google. All were there to comemmorate the life of Dr Alexander ‘Sasha’ Shulgin, a leading pharmacologist who had died from liver cancer in June, aged 88. And those attending the memorial service were by no means the only ones whose lives he touched. He may well have touched yours. Shulgin was the man who gave the world MDMA, descriptively known by its more common name: ecstasy.

After obtaining his PhD from the University of California, Berkeley, Shulgin worked for the Dow Chemical Company throughout the 1960s developing pesticides. His most profitable creation was Zectran, one of the world’s first biodegradable insecticides. The proceeds from this insect repellent were considerable, and allowed him the freedom to pursue his own rogue interests.

A colleague introduced him to a curious compound, 3,4-methylenedioxy-N-methamphetamine, first synthesised in the laboratories of pharmaceutical giant Merck in Germany in 1912. A few animal experiments had produced uninteresting results. Nobody knew much about it. A few scientists had investigated the potential for it to be used as an antispasmodic, but little came out of their studies. Somehow it found its way into American subculture, probably due to its use by the military on psychiatric patients as part of the MKUltra programme. These notorious CIA experiments of the 1950s developed the art of ‘depatterning’ interrogation subjects: breaking them to remake them.

An entire generation of ravers would say MDMA set the tone for their twenties and changed their lives for the better”

Like mescaline and LSD-25, rebellious 20th-century counterculture was introduced to this chemical thanks to military attempts to employ it as an agent of control. And like LSD before it, somehow, the chemical leaked. By the 1970s, rogue underground experimentalists were dabbling with MDMA. The first recorded seizure by police took place in Chicago in 1970.

But it hadn’t hit the big time. Few knew about it – or, more importantly, how to make it.

In 1976, Shulgin reported it had remarkable effects. In the spirit of discovery, he had ingested it. His first MDMA experience was transformative. He became obsessed with the capacity for synthetic compounds to transform human experience, and began to focus his research into their synthesis, structure and effects. He worked for Dow for a few more years, and published reports on his chemical creations in reputable journals such as Nature and the Journal of Organic Chemistry. When Dow grew weary of his druggy pursuits, Shulgin set up shop in his garden shed.

Shulgin created no fewer than 150 new drugs, many in his garden shed laboratory

Shulgin single-handedly crafted thousands of chemicals, of which hundreds were found to be psychoactive. A kooky chemist as well as a gentleman, he always tested every creation on himself first. Then, if it seemed safe, his wife. Then, his friends. Then he would distribute the chemical formula to the public through his website, Erowid. In addition to decoding and broadcasting MDMA to the world, he created the club drugs 2C-B (C10H14BrNO2), 2C-E (C12H19NO2) and a few that behave in weird ways, such as diisopropyltryptamine (C16H24N2) which only influences the auditory system: DIPT is a hallucinogen for the ears.

Shulgin consistently evaded authoritative measures because everything he synthesised was new and therefore uncontrolled. Every time he made and took something he had created, his consumption was therefore entirely legal.

Fearing he would eventually be shut down by the DEA in America, Shulgin self-published his complete chemical compendium – the tale of each molecule’s discovery, its effects and how to produce it – in a two-volume chemical bible: ‘PiHKAL’ (1991) short for ‘Phenethylamines I Have Known and Loved’ and ‘TiHKAL’ (1997), short for ‘Tryptamines I Have Known and Loved’. Both are part chemical textbook, part autobiography; each tome is 800 pages long.

Shulgin is regarded as a hero by some and a menace by others.

The ‘Godfather of Ecstasy’, Alexander Shulgin – with his wife, Anna, in the background – in 2010

An entire generation of ravers would say MDMA set the tone for their twenties and changed their lives for the better. But not everyone had a great time with his chemical concoctions. In 1967 2,5-dimethoxy-4-methylamphetamine, DOM (C12H19NO2), was briefly fashionable in the San Francisco hippy enclave of Haight-Ashbury. A few kids ended up in hospital thinking they would never come down.

Ecstasy was Shulgin’s Number One Hit: throughout the 1980s and 1990s it spread across the planet. As the chemical made an inexorable march through subcultures and into the mainstream, parents worried, authorities disapproved and newspapers screamed.

Just how dangerous is MDMA? Initial studies in monkeys indicated the compound could result in neurodegeneration (permanent deterioration of the electrical highways of the brain). But these have failed to manifest in a generation of human MDMA users, 25 years later. One study indicated the chemical could trigger the symptoms of Parkinson’s – but that turned out to be the result of mislabelled lab samples. The trigger compound was in fact methamphetamine, or crystal meth.

Many of the deleterious impacts of MDMA may simply be due to its combined use with alcohol and other drugs. An intriguing study of Mormon teenagers who had access to MDMA but not alcohol showed no discernible difference in their mental functioning compared with teenagers who had never taken drugs. But due to the clampdown on research following the US Drug Enforcement Administration’s restriction in 1985, MDMA was employed in only a few small studies on depression and anxiety. Neuroscientists could not investigate how the compound affects the human brain.

It is not only licences and red tape which make clinical studies of psychotropic drugs so difficult – the expenses are enormous. How much do you think one gram of medical grade MDMA costs? £500? £1,000? Answer: £5,000. For one gram. Considering you can obtain the compound for 20 quid on the street, it’s a remarkably high price, and makes bona fide research prohibitively expensive. “The ultimate effect of all these rings of red tape is to harm the science,” says Dr Robin Carhart-Harris of Imperial College London, who conducted one of the world’s first studies of psilocybin on the human brain using MRI scanners.

“Science is hard: it requires special licences and regulations, and most people just don’t have the patience for it – it is utterly tedious sometimes,” says Professor David Nutt, director of the neuropsychopharmacology unit at Imperial College London. You may know him as the man fired by the British government for statistically demonstrating that taking ecstasy is less dangerous than horse riding.

Professor Nutt’s use of magnetic fMRI scans revealed patterns of brain activity induced by MDMA that had not been seen before: a decrease in the ‘synchronous firing’ of two regions, the prefrontal cortex and the posterior cingulate cortex.

In people who suffer from clinical depression, these two locations are known to synchronise their firing more tightly, which many neuroscientists think correlates with ‘ruminative’ thought patterns. Spinning round and round, dwelling on negative ideas, memories and feelings. Trapped in an emotional vortex. You’ve probably been there.

Shulgin himself used his compounds to feed his spirituality and as a tool for research. And many who spoke at his memorial service in Berkeley felt that he had helped them to open their eyes and expand their minds. Paul Daley, a research scientists and former colleague of Shulgin’s, summed up the sentiment best: “It breaks my heart that we’re missing him now, but somehow it seems that Sasha Shulgin is now tripping in the cosmos somewhere.”

Zoe Cormier is the author of ‘Sex, Drugs and Rock ’n’ Roll: The Science of Hedonism and the Hedonism of Science’, published by Profile Books. 

Posted on Wednesday, October 18th, 2023 - Categories: #16 - Jul-Sep 2014, App Issues.