The Shopping List

I

In 1976, in a garden shed at a house in California, a fifty-one-year-old chemist synthesised a substance that had been patented and forgotten for sixty-four years, and took it.

His name was Alexander Shulgin. He had worked at a large chemical company, where he had invented an insecticide that made a great deal of money, and with that standing he had obtained something unheard of: a federal licence to work with controlled substances in his own domestic laboratory.

The shed had cobwebs and second-hand equipment [a domestic laboratory with a federal licence, which is a combination that does not exist today]. In there he synthesised and tested more than two hundred compounds over the course of his life.

The method was always the same and he had it written down. You began with a ridiculous quantity, far below any expectable effect, and worked upwards in sessions separated by days, noting the hour of each dose and of each change. First him, then his wife, Ann, and then a group of ten or so friends who had been doing the same for years —with a scale of intensity they had invented themselves—.

Of that substance he wrote that it produced “a window” and that it seemed to him useful for talking, emotional clarity, no hallucinations.

He did not invent it. A German company had synthesised it in 1912, as an intermediate for making something else [the patent does not claim it as a drug], and it went sixty-four years without anyone knowing what it was good for.

II

What Shulgin did next is what makes this case different from a laboratory anecdote.

He showed it to a retired psychologist, Leo Zeff, who was working with assisted therapies. Zeff came out of retirement and spent the following years teaching other therapists how to use it in session [he is reckoned to have trained several thousand].

Between 1977 and 1985, that substance was used in consulting rooms, legally, without a single controlled clinical trial on it existing.

Then it left the consulting room. It began to be sold in Texas bars under a trade name and by credit card, it appeared in the press, and in 1985 the federal authority banned it as an emergency measure [schedule one, that of substances with no accepted medical use], against the finding of its own administrative judge, who had recommended leaving it available on prescription.

With the ban the two things ended at once: the therapeutic use and the possibility of studying it.

It took thirty years for there to be authorised trials again.

III

I have not taken it and the part that falls to me to tell is the room.

I have been many times in places where half the people were carrying something inside, and what is seen from outside is fairly monotonous. Jaws working. People drinking water from half-litre bottles they leave everywhere. Long embraces between people who have just met. Very intense conversations by the toilets, at four in the morning, that nobody remembers precisely the next day.

Entry with a drink cost twenty euros. The rest I do not know, because I have never bought it.

What I have seen is the Tuesday. There is a crash that arrives two or three days later, with people odd, touchy, sleeping badly and saying they are never going out again, and it is so predictable that it has a name among those who do it often.

That is the only thing I can contribute, and I put it in because to describe from inside an experience I have not had would be exactly what this series tries not to do.

IV

Inside, this molecule does something almost no other does. It does not block the collection of a signal, it turns it inside out.

In a neuron that works with serotonin there is a pump on the surface whose normal function is to collect from the gap what has been released and put it back inside to be reused. There are drugs that sit on top of that pump and occupy it; then the serotonin that had already come out stays out longer.

Not this. This molecule enters the pump and travels with it into the cell, and once inside it makes the pump work in reverse and start pouring serotonin out, without waiting for any signal.

It is not an increase in the normal conversation between two neurons. It is an emptying.

Since the store is emptied, afterwards there is nothing left. Replacing it takes days, and in those days the mood is below its baseline; it is what people describe as “the Tuesday”.

It also does two other things that matter, and both explain newspaper headlines. It releases oxytocin, which is the signal associated with bonding and contact, which explains the social part of the effect better than any psychological theory. And it raises body temperature and blocks the sensation of thirst in some cases, which is the combination that has killed people at parties.

The body, meanwhile, does what it can: the liver goes on dismantling it, and in that process produces fragments that at high and repeated doses can damage the very terminals that released the serotonin.

V

What interests me about this file is not the substance.

It is the window. Between 1977 and 1985 there were eight years in which a molecule was used in therapy, in a whole country, without anyone having run a controlled trial, and then there were thirty years in which it could not be studied even if one wanted to.

The two situations are the same class of error with opposite signs, and both come from the decision not having been taken by the evidence; it was taken, first, by a group of convinced therapists, and then by an administrative emergency procedure.

Today there are trials, there are results and there is argument about their quality [one regulatory agency has already rejected an application over design problems]. That is what there was not for forty years, and that absence is not the molecule's fault.

VI

The objection is easy to formulate and hard to sustain in either direction.

Shulgin experimented on himself, on his wife and on a group of friends who signed off what they did and kept a scale of intensity invented by him. That is not a clinical trial and he never said it was; he published two enormous books with the formulas and the doses, and those books are at once a unique scientific archive and a manual anybody can use.

I do not know how to resolve that and I am not going to pretend I do.

What I can say is the same as in the piece about the Swiss man with the bicycle: the body in the archive is better documented than mine. He noted hour, quantity, duration and effects for forty years. I have looked at a dance floor.

VII

Shulgin had a stroke in 2010 and died in 2014, at eighty-eight, in the same house where the shed was.

His notebooks are kept and have been digitised.

What is in there is forty years of one same routine: date, compound, quantity in milligrams, hour of the dose, hour of the first effect, duration, notes. Two hundred and some substances, many invented by him and synthesised for the first time in that shed, tested on the same body that made them. The federal licence had been withdrawn in 1994, after an inspection; he was fined and went on working without it.

1912, patented as an intermediate and forgotten for sixty-four years.

1976, the first dose in the shed.

1977 to 1985, eight years of use in therapy without a single controlled trial.

1985, emergency ban against the finding of the authority's own administrative judge.

Thirty years until the first authorised trials.

Entry with a drink: twenty euros.