The Drugs That Changed Our Minds

by Lauren Slater

  Others, meanwhile, continued to disagree. ‘We’ve seen thousands of people safely use MDMA, sometimes as many as forty times or more,’ said Julie Holland, who for a time ran the psychiatric A&E department at Bellevue Hospital in New York, and has seen hundreds of drug-related emergencies. ‘There was nothing about the Ricaurte study that seemed plausible to me, and I can tell you, based on everything I’ve seen, based on the published data and my clinical experience, MDMA is just not a significant cause of psychiatric crisis.’ Doblin, too, was left scratching his bald spot. But it didn’t take long before someone started to poke around in Ricaurte’s study and a grave error was uncovered. Ricaurte, it turned out, had not given MDMA to his orangutans and bonobos. He’d given them an entirely different drug – methamphetamine, a known toxin – dosing his subjects with large amounts, watching as their brains sizzled, and then saying the damage had been done by MDMA.

  How could this have happened? Ricaurte reported that his supplier mislabelled the bottles, while his supplier counterclaims that it has never mislabelled its bottles. Ricaurte was forced to issue a retraction, but in a way it didn’t matter; the damage was already done. Millions of Oprah’s viewers had seen the images, while very few of them saw the published retraction. ‘The Ricaurte study has definitely added to the stigma and misinformation around MDMA,’ Doblin said. ‘It has become part of our uphill battle.’

  After Ricaurte published his retraction, the DEA gave the go-ahead to Doblin and Mithoefer for their research. That 2011 study has given rise to four others, including one in Boulder, Colorado, where the results have been promising. Of the twenty-eight subjects who were enrolled, three-quarters of those who received an active dose as opposed to a placebo achieved remission; they no longer met the diagnostic criteria for post-traumatic stress disorder. This, combined with a study of Mithoefer’s in which subjects were followed for as long as forty months and were still holding strong, suggests that while MDMA might be a quick high, it’s also no quickly fading cure. The positive press the post-traumatic stress disorder–MDMA experiments have generated has gone a way towards undoing some of the damage caused by Ricaurte’s megaphone. Doblin now wants to focus all his efforts on getting the DEA and the FDA to legalise MDMA for the treatment of posttraumatic stress disorder and, prior to that, getting permission to conduct more studies replicating the findings of the first few.

  Seeking MDMA

  Doblin was quick to acknowledge that MDMA has many applications beyond the treatment of post-traumatic stress disorder. But despite the breadth and depth of MDMA’s potential, he said he and his researchers would not be pursuing most of these paths right now and, with the exception of MDMA for life-threatening illnesses and the treatment of social shyness in autistic adults, probably not anytime soon either.

  This disappointed me, and for a very personal reason. When I first spoke to Doblin, the marriage to my husband that has now ended was in its denouement. But I wasn’t ready for our story to be over. After everything I had read, I was ready to try a tablet or two of MDMA with my husband. It was cheaper and faster, I reasoned, than taking the two-month holiday we would otherwise have needed to find our way back to the long-lost but not completely forgotten love we once had. Yes, I thought, we were perfect candidates for a blind date with an empathogen. But as it turned out, I probably wasn’t about to be making these discoveries, at least not through a MAPS-funded study, and right now that’s the only option there is in this country, at least of the legal variety. Of course my husband and I could have tried ‘scoring’ some of this stuff on our own, but I didn’t want what comes off the street.

  ‘Where is the MDMA anyway?’ I asked Doblin. ‘When the DEA gives you permission to do a study, where do you get the drug if it’s illegal?’

  The answer? Purdue University, where it was made in 1985 with a DEA licence by David Nichols, the former chair of pharmacology at Purdue. ‘MDMA’, Doblin explained, ‘is an extremely stable compound’, which means there’s a big glass bottle full of the substance that’s been sitting on a shelf in a chemist’s locked safe in an institution of higher learning for years. Impervious to heat, cold, light and darkness, the chemical doesn’t break down. In this sense it’s unlike most other medications, which come in bottles with use-by dates stamped on their sides. I find it ironic that ‘ecstasy’, a state known more for its passing than its actual emotion, is, in its molecular form, something so very solid.

  There was an awkward pause in my conversation with Doblin and I felt my face beginning to burn and at first I wasn’t sure why, but then the question formed. ‘Would you consider getting some for my husband and me to try?’ I couldn’t believe I was asking him this. Think about drugs too much, I guess, and you start to act like you’re on them.

  Doblin and I were sitting on the roof deck of his home in Belmont, Massachusetts. It was one of those gorgeous days on the cusp of autumn, before any of the trees have begun to turn, the air cooled, the greenery lush and verdant. Somewhere a dog was barking, and music came from the house next door.

  Before he could answer I said, ‘I’m on other medications, like Effexor [venlafaxine], for depression,’ to which Doblin replied, ‘You can’t take MDMA with an SSRI.’

  He explained why but I wasn’t listening. Or rather I was, but to something else. I was listening to the neighbour’s radio and to the staccato barks of the dog, and pondering the disappointment I felt in Doblin – that despite all its potential myriad purposes, all the various and significant ways MDMA could help people connect, he and his agency were pursuing only one. I was remembering something he had said to me moments earlier, about how post-traumatic stress victims – war veterans, survivors of violent rape – make MDMA seem like a serious, even patriotic drug, whereas couples counselling reverberates with echoes of hippiedom, which is what Doblin above all wants to avoid. ‘Marriage can’t be conceived of as a disease,’ Doblin had said to me, ‘so how could we devise a study if there’s no discrete set of symptoms to increase, decrease or stabilise? Beyond that, couples counselling just doesn’t carry the weight, the import, in the public’s eye, and we need to think a lot about the public, and that eye.’

  I could appreciate Doblin’s reasoning, and the difficulty of the dual roles he needs to play here, part researcher, part PR manager, tiptoeing carefully along. ‘My life’s goal’, he said, ‘is to see the psychedelics made into prescription drugs.’ He hoped to see this happen by 2021. But for now he had picked just a portion of that goal to focus on: post-traumatic stress disorder, with MDMA as the treatment. And I understood why, even as I disagreed with him about whether marriage can be quantified for the purposes of research. Surely there must be some scale somewhere out there that captures, for instance, the symptoms of a failing marriage, some way to measure the marriage pre- and post-MDMA ingestion.

  ‘I’m going to find you a measurement device,’ I told him, ‘and if I can’t find you one, I’ll make one.’ Doblin laughed.

  We were at that point when the summer’s end feels palpable, the smell of autumn everywhere in the air. The sun was slowly sinking as we spoke, inching down bit by bit, so slowly you couldn’t even see it and wouldn’t notice until, suddenly, there were shadows everywhere and it was evening – just like that. This is how many marriages devolve as well, the shine waning so subtly no one notices until one day in year twelve of your marriage you can’t rinse the stale taste out of your mouth, and when you try to trace the path that got you here, all you see are seemingly festive landmarks: babies born, first day at school and so on. And then somehow it has been two decades.

  I don’t want to argue the case that divorce is a disease or that a failing, faded marriage is the same as a sickness, because that is a subject that goes, as the scientists say, ‘beyond the scope of this paper’. But even if divorce is not an illness itself, it does leave a trail littered with symptoms and syndromes – the depression, for instance, that so often comes when a dyad dissolves, or the generalised anxiety disorder that some childre
n experience when their parents go their separate ways. I’m rooting for a return, of sorts, to a time when MDMA was used by therapists like Shulgin and Zeff to treat marriages at their breaking point. And while Doblin may wish to steer clear of ‘the soft stuff’ and reserve MDMA for those decimated by a particular kind of distress, there is a part of him that understands how wide the reach of MDMA could, and perhaps should, be. I know this because he gave me the name of a practitioner who uses MDMA in her therapeutic work with couples.

  I drove out to see her. I told her I was on the edge of divorce, and that the edge felt bad – shaky and sharp both. Her office was filled with flowers, trillium and irises and lilies with long golden tongues. She had a statue of a laughing Buddha and somewhere a fountain burbled and splashed. Her hair, blonde and flowing, put me in mind of a pelt. I wanted her to simply give me two tablets, one for him and one for me, but she wouldn’t do that. Instead she wanted the whole sorry story of our decline, and even after I’d told it to her, over a series of weekly visits, she still wouldn’t give me the goods.

  ‘You may be too sensitive,’ she said, ‘and given all the medications you’re on I’d have no idea how to dose you.’

  ‘Let’s start small’, I said, ‘and go from there’, but she wouldn’t do it and eventually I lost interest in trying. I’ve never taken an empathogen, or any other type of psychedelic for that matter, and it seems like such a loss to me. Could MDMA really have saved my marriage, or would it have been just another chemical tool added to my already considerable stash? I have no way of knowing.

  In the meantime the season continued to change. The leaves were all coming down. The days were shorter and then shorter still until at last the sky was daily drained by four in the afternoon, with the tiny spot of the sun setting and the frost stiffening the grass and glazing the masses of fallen leaves. What can we do when we are lost to each other, when the temperature plummets, when the snow blinds us to even the familiar landmarks? Someday. Somewhere. Somehow. This is what I tell myself. Delic: to open. Maybe I don’t need a drug to see the wonder of the world, but I also didn’t need a drug to see the relationship dissolving, going to pieces, falling in flakes at our feet.

  Divorce may not be an illness, but it sears the soul all the same. I dream that we will one day meet and that, spurred by MDMA, we will recover the love we lost, even if only for an afternoon. I’d like him to see me as he once did, and vice versa. I’d like to be twenty-four, not fifty-four. Someone once told me that she took MDMA and all she did was weep. That is a possibility. Still, I want to see through that oxytocin-soaked lens. In the meantime I’ll wait. If Doblin’s goal is to make MDMA a legal prescription medicine by 2021, then I really have only four years to go. By then, who knows, we both may be remarried. But there’s enough love here that it deserves to be recalled, if not rekindled.

  8

  PKMzeta/ZIP (Memory Drugs)

  The Spotless Mind

  Memory Erasers

  Strange things were happening to me. When friends came to visit I’d say, ‘Let me show you around’, and the odd way they looked at me let me know I’d already given them the grand tour of my new home months, weeks, maybe just days ago. The house felt to me like a maze, all crooked corridors and dark doors, a floor plan I couldn’t seem to memorise even after we’d been here for six whole months, long enough to learn the layout of a bungalow with four bedrooms and two bathrooms ugly enough to want to forget. ‘Let’s redo those bathrooms,’ I’d say to my husband, and then I’d launch into my design ideas and he’d ho-hum, having heard it all before. But when? My mind, it seemed, was going the way of the wood I coveted – gnarled and pitted, washed out by weather. It felt as if there were ragged holes in my brain through which both fact and fiction were swiftly falling.

  In an increasingly ageing society – in England and Wales, according to the Office for National Statistics, the aged sixty-five and over population increased from 8.3 million in 2001 to 9.2 million in 2011, an increase of 11 per cent – memory is more than a hot topic of conversation. While I may be showing some form of early cognitive decline, it won’t be long before my contemporaries have to acknowledge that their brains aren’t as shiny as they once were either. Our collective ageing, and the huge profit potential for clinical interventions that slow or even reverse age-related forgetfulness, has researchers on the fast track to find a cure for the dreaded Alzheimer’s and its companion scourge, mild cognitive impairment (MCI), a condition that frequently develops into Alzheimer’s.

  Memory research, however, is about much more than Alzheimer’s. Scientists are using fMRIs to peer deep into our mental machinery, and studying the brains of fruit flies as well, all in an effort to better grasp not only how we remember but also how we forget. The goal is to create a drug that can be administered to addicts or trauma survivors. While MDMA can change the emotional tone of trauma so that the memory no longer sears or scares, some scientists are looking to go even further by developing a drug capable of completely erasing a frightening incident, or, for addicts, of wiping out a series of recalled ingrained associations and behaviours that they have been unable to shake.

  Current memory research, then, reflects our own contradictory needs. We are, on the one hand, a society terrified of losing our past, while at the same time we seek the means to wipe our slates clean – if not the whole blackboard, then at least those nightmare scrawlings: whether it’s the collective trauma of a serious terrorist attack or disaster or the personal trauma of the rape in the rain. We covet a memory scrubber so specific, so technologically savvy, that it can cleanse certain spots while leaving the rest of the plot untouched. At the moment this is just a dream, an ambition, what the scientists are stretching towards as they probe for ways of helping us navigate the minefield of memory, both when it wanes against our will and when it clings, keeping us spellbound by something we’d rather be rid of.

  But just because scientists haven’t yet managed to work all the magic we might wish for doesn’t mean they haven’t come up with some pretty amazing discoveries about memory. Alain Brunet, for example, a clinical psychologist at McGill University in Montreal, had a hunch about a common drug that he believed could be repurposed into a mental eraser. Unlike MDMA, which is illegal without a special permit and therefore impractical for scientists to obtain, Brunet’s drug is readily available including in the United States and the UK. The drug is called propranolol, a commonly used beta blocker prescribed for those suffering from high blood pressure or, in other cases, performance anxiety. The drug works by blocking the action of the chemical noradrenaline, which is involved in arousing strong emotions, particularly during fight-or-flight mode. Brunet understood that traumatic memories retain their power because every time we recall the event, we reactivate our fear circuitry – the clammy hands, the rapid heartbeat, the high startle response. What would happen, Brunet wondered, if he could get traumatised subjects to recall their terrible and terrifying stories while simultaneously suppressing the fight-or-flight response that keeps the trauma potent?

  Unlike MDMA, propranolol does not raise levels of oxytocin, a hormone that, as we’ve seen, promotes feelings of peace and love, but propranolol does inhibit adrenaline, thereby allowing trauma survivors to remember with less fear. In 2011 Brunet administered propranolol to nineteen traumatised patients, asking them first to write a detailed description of their trauma before ingesting the drug. He then waited one week and had his subjects return to his laboratory, whereupon he exposed them to their own written descriptions of the traumatic event. Subjects who had ingested a placebo appeared as traumatised as ever, but those who had taken the beta blocker seemed changed. Upon hearing their tales of trauma read out loud, they showed significantly reduced stress responses. Brunet and other scientists in the field believe that the beta blocker works to dilute traumatic memories by suppressing the fear and anxiety associated with them so that the memories no longer kick the amygdala – the fear centre in the brain – into overdrive.

/>   While propranolol is not a ‘forgetting tablet’ – it doesn’t destroy memory but instead alters its emotional overtones – it was a big advance and provided the platform for what came next. The following year, in 2012, when I first spoke to neuroscientist Todd Sacktor, he was busy studying the tiniest particles of chemical compounds associated with remembering and forgetting in a laboratory in Brooklyn. Sacktor’s father was a biochemist who had suggested to his son, almost three decades earlier, that he should take a look at a group of molecules called protein kinase C. Sacktor listened to his father and began investigating the enzymes, taking three years first just to purify and isolate them before eventually discovering that PKMzeta, a type of protein kinase C, has a star role in making our memories work the way they do.