The Drugs That Changed Our Minds

by Lauren Slater

  In the early 1970s, Stanford University professor and psychologist David Rosenhan devised an ingenious experiment to illustrate the flimsy nature of the psychiatric diagnosis. He rounded up seven colleagues, plus himself, and they dispersed to various mental hospitals around the country, whereupon they presented themselves as hearing a voice that said ‘thud’, ‘empty’ and ‘hollow’. This was the sole symptom that these pseudo-patients complained of; they otherwise acted completely normal. On the basis of this single ‘symptom’, all eight of the pseudo-patients were admitted with a diagnosis of schizophrenia, with the exception of one who was diagnosed with manic-depressive psychosis. The pseudo-patients were held on their respective wards for an average of nineteen days, during which time they acted as they always did. They took notes, which the staff tended to consider part of their pathology (‘patient engaged in writing behaviour’, wrote one ward nurse), and never once did any mental health specialist suspect them of faking. The actual patients, by contrast, caught on quickly to the ruse, accusing the pseudo-patients of being journalists or professors checking up on the hospital. Once all the pseudo-patients were released, Rosenhan published his results, causing quite a ruckus in the field, as he had for all intents and purposes proved that psychiatric diagnosis was entirely unreliable and scarily subjective, with almost no validity.

  This got under the skin of one psychiatrist in particular, Robert Spitzer of Columbia University in New York, who made it his sole mission to overhaul the entire manual, coming out, in 1980, with the third edition of the DSM, which was decidedly different from the two earlier versions in that it attempted to yield a picture more akin to a statistical population census rather than relying on simple psychodynamic diagnoses. Spitzer broke human suffering into quantifiable chunks, listing, for instance, all the known symptoms of major depression, of generalised anxiety disorder, of psychotic disorders, and including instructions to clinicians as to how many symptoms the patient needed to have to qualify for any given diagnosis. Spitzer and company effectively made a diagnostic manual that had real reliability – but it didn’t have any more validity, and there’s the rub. The description of depression, just like every other diagnosis, was decided upon by a committee subject to whims and agendas. And still today you will not find in the DSM any understanding of why, only how. The manual describes all sorts of suffering but utterly fails to illuminate the roots and reasons.

  For the latest iteration, the DSM-V, published in 2013, a group of neuroscientists, biological psychiatrists and prominent doctors petitioned the DSM-V’s mood disorder committee to consider a new diagnosis that they were calling by a very old name – melancholia. Melancholia has been around for a very long time, so long that Hippocrates wrote about it, attributing the phenomenon to an excess of black bile. The petitioning practitioners believed that the absence of melancholia in the DSM-V would be a great oversight, as it has symptoms distinctly different from other kinds of depression, like dysthymia, for example, for which low-grade dejection is the defining descriptor. In melancholia, the patient shows not only psychological symptoms, such as a guilt-ridden psyche and deep despondency, but also physical symptoms such as psychomotor retardation – a slowing of the body and the mind – and distinctly disturbed sleep patterns, along with a metabolism of the stress hormone cortisol gone into ‘overdrive’, decidedly different from that of non-depressed people and people suffering from other types of depression. Unlike with other symptoms of depression, there is an actual way to test a person’s level of cortisol. The dexamethasone suppression test (DST), which is capable of measuring stress hormones like cortisol, may therefore be perhaps the first actual objective biological measure of a mental illness, something psychiatry has long been searching for. ‘If melancholia wasn’t the Holy Grail’, said writer and therapist Gary Greenberg, ‘it was at least a sip from the chalice of science, one disorder that could go beyond appearances.’

  The mood disorder committee of the DSM-V, however, was not open to adding melancholia to its types and subtypes of depression, despite the fact that it would have provided the field at last with one physiological test proving that at least one mental illness is a medical disease. Committee member William Coryell wrote to the petitioning practitioners, telling them he believed they were correct but that ‘the inclusion of a biological measure would be very hard to sell to the mood group.’ Why? The problem, explained Coryell, was not the DST’s reliability, which Coryell believed was very high, but rather that the DST would be ‘the only biological test for any diagnosis being considered.’ The result, wrote Greenberg, was that ‘the main obstacle was exactly what you would think was melancholia’s strength: the biological tests, especially the DST . . . A single disorder that met the scientific demands of the day, in other words, would only make the failure to meet them in the rest of the DSM that much more glaring.’ The committee of the DSM-V had the chance to step into the psychiatry of the future and turned it down, falling back on patterns of the past.

  Indeed, the past may be where psychiatry is content to live for however long it lives, given that, according to psychiatrist Richard Friedman of Cornell University in New York, no novel drugs have come through the pipeline in thirty years. There were the mostly serendipitous and stunning drug discoveries that this book has endeavoured to describe, the majority of which occurred between 1949 and 1959, and then fluoxetine broke the blues in 1987. But in the long run, even that medicine turned out, despite the huge hype, not to be really any more effective than the tricyclics had been.

  I personally find it difficult to believe that we have now gone decades without any true innovation in psychotropic medication. Within the cocoon of my own experience, the tricyclics were dry-mouth duds, while fluoxetine spun me around twice and then took me to the dance, where I waltzed away my thirties in a state of such supreme happiness that I was legitimately worried. And it turns out I had something to be worried about. Even setting aside the warnings of Robert Whitaker and Joseph Glenmullen about the lack of knowledge regarding the drug’s long-term side effects, the problem for me was that the drug wore off – or I developed a tolerance to it, call it what you will. I needed more and more of those pretty tablets, until at last my dose was both sky-high and ineffectual.

  Psychiatry’s answer to the problem of tolerance is to practise polypharmacy. For me, as for so many others, this meant two things. First, I switched from an SSRI to an SNRI, venlafaxine, a drug that tickles the noradrenaline receptors as well as the serotonin receptors, and then I also went on a second drug, an antipsychotic that was meant to enhance the efficacy of the venlafaxine. I don’t think, however, that psychiatry’s future is in polypharmacy, in doping up patients on a little of this and a lot of that and sitting back to see what happens. But I don’t totally agree with Friedman and others, either, when they say that no novel drugs have come down the pipeline in thirty years. While it may be accurate in a strictly technical sense that there has been little or no recent actual invention in the psychotropics, the truth is that there has been significant innovation. There are groups of psychiatrists doing amazing things way out on the edge, not necessarily with new drugs but with old, even ancient drugs, which they are using in undoubtedly novel ways. I think the future of psychiatry is, strangely enough, right here, in tiny tabs of acid and chalices of psychedelics such as ayahuasca, psilocybin and MDMA.

  We’ve seen already how Alicia Danforth and Charles Grob have enabled many autistic patients at University of California, Los Angeles (UCLA) to experience, for the first time, what it is like to interact with the neurotypical world without fear. The beneficial effects of these experiences last well beyond the actual ‘high’. MDMA, as we know, has already proven to be incredibly effective for those suffering from post-traumatic stress disorder, and Danforth would also like to see it utilised for borderline personality disorder (BPD), a diagnosis often given to young women who have an extreme fear of abandonment, who self-harm and who experience perpetual feelings of emptiness. It is a condi
tion marked by self-hatred and an impaired ability to connect. In the psychiatry of the past, borderline personality disorder was a condition one either grew out of or failed to; the psychiatry of the future, however, has a potential answer to borderline personality disorder with MDMA, offering those suffering from borderline personality disorder a new world view in which their worth is protected and preserved and regard for self and others can be kept totally intact.

  The intrepid practitioners out on the far fringes of psychiatry who are turning to ancient or synthesised psychedelics are finding that these drugs make a real difference for those suffering from a broad spectrum of afflictions, from autism to addiction to posttraumatic stress disorder to depression to fear of death as well. Although there are several different psychedelics currently being tested with different populations of patients, they all seem to offer the subject the same thing: insight. The psychedelics allow patients stuck in self-destructive patterns of thought or behaviour to view themselves and their role in the universe in a radically different light. They appear to illuminate death, or the limit of life, and in so doing to underscore its preciousness. Time is both highlighted and obliterated, so that patients can truly grasp that although they live in a timeless universe, they have just a short amount of it on this Earth in which to love and to work. Psychedelics like ayahuasca, made from vines and leaves, allow patients to see the uselessness of their alcohol or drug abuse and, by increasing their empathy for others, how their behaviour may be hurting those close to them. Thus a fresh resolve is born.

  The newest psychedelic that psychiatry has turned to is ketamine, known on the streets for many years as ‘Special K’. It is a drug employed by anaesthesiologists during surgeries, but starting in the 1990s some researchers began to investigate whether ketamine had the ability to improve mood, and to use it when all other treatments had failed. Ketamine, which is usually delivered to the body via IV infusions in clinics that are popping up with increasing frequency around the United States, is deeply different from standard antidepressant treatments. Right now ketamine infusion therapy is reserved for only those patients who are treatment resistant, who have tried numerous other pharmacological combinations over months and years, and have undergone intermittent shock treatment, all to no effect.

  Suicide is on the increase, with thousands of people living in the UK committing suicide each year, and those who kill themselves are often suffering from treatment-resistant depression. Currently, select treatment-resistant patients can go to their closest ketamine clinic in the United States, which may not be run by a psychiatrist at all but by an anaesthesiologist who has had years of practice dosing patients in the operatiang theatre. And instead of being handed a prescription, they are led to a lounge chair, where a needle is inserted into a prominent vein, and then, over the course of forty-five minutes to an hour, they are infused with the drug, experiencing perhaps some dissociation although rarely any hallucinations, perhaps a bit of dizziness or confusion but nothing so severe that they aren’t fit for discharge within an hour and a half to two hours. They can’t drive or operate a bulldozer directly after ketamine treatment, but this, one imagines, is a very small price to pay.

  What’s most remarkable about ketamine so far is the speed with which it works. Unlike traditional antidepressants, ketamine comes on right away, wiping away the sludge of despair within minutes or hours of the infusion. How long does this relief last? The answer is not clear yet. It’s too new. Most patients receiving treatments at a ketamine clinic will go back for a series of four to six infusions over a twelve-week period and then return for boosters on an as-needed basis. Ketamine may well be the future for the treatment of depression in psychopharmacology. It can be taken and tolerated with many other drugs, meaning you likely won’t need to detox off any other medications you may be imbibing in order to qualify as a bona fide ketamine patient.

  As with all other psychiatric drugs, no one really knows why ketamine works, and especially why it works so swiftly. Some theorise that the drug is neurotrophic, meaning that it allows neurons to sprout new connections to neighbouring neurons, essentially remaking your brain, which can then, post-treatment, suddenly see life in a whole new way. Within minutes after an IV infusion of ketamine, the brain gets busy sending out its sprouts, pathways that ferry new and adaptive cognitions and images from one neuron to the next, and that express themselves as the lifting of a dark and despairing mood. These potential neurotrophic abilities of ketamine make it different from the other psychedelic drugs I have investigated here, none of which, as far as anyone knows, can actually prompt the brain to send new sprouts throughout its rumpled mass. And while there have been one or two studies of psilocybin for treatment-resistant depression, ketamine is the first psychedelic to be used specifically for this purpose, meaning it’s poised to have a remarkable impact, as depression affects huge swathes of people. One study even shows that ketamine can effectively reduce or altogether eradicate suicidal thoughts. But it’s a treatment so new that although there has been some research, the US Food and Drug Administration (FDA) has not yet granted approval for the drug. Legal use of ketamine is restricted in the UK, where it is mostly used as an anaesthetic but in limited cases it may be available in low doses to help relieve pain.

  Rick Doblin, as we know, has said his goal is to make psychedelics – especially MDMA – legal prescription medicines by 2021. On the one hand, this is a hugely ambitious goal, and seems like a leap across too wide a barrier, given that all psychedelics are classified by the US Drug Enforcement Administration (DEA) as having ‘no currently accepted medical use and a high potential for abuse’. And yet without a doubt there are subterranean shifts and stirrings. As of November 2016, the FDA is allowing MAPS to move into phase-three trials of MDMA-assisted psychotherapy for post-traumatic stress disorder. Thus it is here, in this psychedelic corner, that psychiatry is truly rejuvenating itself, not only eliminating the unhelpful dregs of psychoanalytic theory but also stepping out from under the bland blue fluoxetine sky and into a place where mysterious and mighty chemicals, illegal chemicals that carry with them the aura of the 1960s counterculture, are being resurrected with extreme caution and just a little bit of glee, so stupendous are their effects.

  The psychedelics provide psychiatry with a whole new model of how drugs might work, and a whole new way to think about psychopharmacology. In our current model a patient takes a drug, or many drugs, daily, a fact that has hugely benefited pharmaceutical companies, which stand to make billions off our distress. Were psychedelics ever to become more widely adopted than SSRIs and other antidepressants, the huge money-making pharmaceutical houses would be greatly reduced, replaced with small non-profits like MAPS, which would dole out drugs with little potential for profit, because one need not take them regularly to get a beneficial effect, and because, like lithium, they are, at least some of them, naturally occurring.

  The psychopharmacology of the future should be genuinely insight-oriented, and in that sense would, ironically, represent a step back into the past. One takes a chemical with the powerful and profound ability to turn the mind inside out, and then spends ten straight sessions talking about the lessons learned. Many researchers, including the Pulitzer Prize winner Siddhartha Mukherjee, an oncologist at Columbia University in New York, have noted that even in antidepressants the best results tend to come when medication is combined with talking therapy. The reason for this is not entirely clear. ‘It is very unlikely that we can “talk” our brains into growing cells,’ Mukherjee wrote. ‘But perhaps talking alters the way that nerve death is registered by the conscious parts of the brain. Or talking could release other chemicals, opening up parallel pathways of nerve-cell growth.’ But whatever the reason, it is a deeply divergent model from the one we have now, in which patients are tethered to their doctors by once-monthly visits whose purpose is simply to renew the prescriptions. Psychedelic treatment, despite its past stain and stigma, offers psychopharmacology a chance for deep dignity a
s its practitioners accompany patients to the furthest reaches of their minds, with the doctor recast as guide, a medical man or woman who does so much more than swiftly write out a prescription.

  In the future, then, psychiatrists might be shamans or, the other way around, shamans may act as psychiatrists, counselling people during and after their trips. The lingo of the DSM might be replaced with phrases like ‘set and setting’. Patients might be instructed to come to psychedelic sessions with photos of loved ones or meaningful mementos, any object that can facilitate a profound psychedelic journey. I doubt the DSM will be wiped out, or that conventional antidepressants will go the way of the wind, but there’s a reasonable chance that they will become adjuncts to treatment rather than the sole focus. Such a change would be huge not only for patients accustomed to monthly medicine checks but also for psychopharmacologists, who would be remade in the role of divine guide. I have no doubt that many would reject that role, which may be why MAPS is currently training therapists in how to conduct psychedelic sessions, so that if the rejuvenation were to happen, we would be ready.

  I myself would be ready. In fact, I already am ready. Despite my initial failure to procure MDMA, I decided several months ago to look into psychedelics once more and went to see a therapist who uses them in her treatment. She would give me only her first name and the address of her office, which was located in a cramped corner of the city, up a flight of stairs. As with the earlier practitioner, the walls of her treatment room were painted calming colours, and there was plenty of oriental decor and a lot of flowing fabric. After I had listed for her the drugs I’m on and told her something about my history, which includes several stays in psychiatric hospitals (although none in the past thirty years), she thought better than to give me psilocybin, the drug that I was seeking this time.