Who gets to trip?

‘Wouldn’t you like​ to see a positive LSD story on the news?’ asked the late comedian Bill Hicks in one of his most famous routines. ‘Today, a young man on acid realised that all matter is merely energy condensed to a slow vibration – that we are all one consciousness experiencing itself subjectively, there’s no such thing as death, life is only a dream, and we’re the imagination of ourselves. Here’s Tom with the weather.’ It’s a shame Hicks was no longer around to see the Washington Post headline in 2016 claiming that ‘LSD could make you smarter, healthier and happier,’ or Men’s Health explaining in June last year ‘why LSD is your new Monday pick-me-up’. The psychedelic medical breakthrough has become a news staple: psilocybin for end-of-life care, magic mushrooms for OCD, ketamine for depression, ecstasy for PTSD, ayahuasca for addiction. The stories seem to write themselves: a dad-joke about hippies, or tie-dye or the Grateful Dead, followed by a grand claim that psychedelics are poised to revolutionise the treatment of mental illness with a quote from the lead researcher and an announcement of larger trials to follow.

That such stories find favour in the attention economy reflects the success of the researchers and campaigners generating the stories. Early in his survey of ‘the new science of psychedelics’, Michael Pollan talks to Rick Doblin of the Multidisciplinary Association of Psychedelic Studies (MAPS), pioneers of therapeutic research into MDMA, LSD and ayahuasca, who is candid about his choice of the medical paradigm as ‘a means to a more ambitious and still more controversial end: the incorporation of psychedelics into American society and culture, not just medicine’. In Blue Dreams, Lauren Slater’s account of the past, present and future of psychiatric medicine, Doblin explains why, despite the considerable early promise of MDMA use in relationship therapy, he decided to focus his research instead on the treatment of post-traumatic stress in veterans. ‘Marriage can’t be conceived of as a disease,’ he explains, whereas treating army vets transforms the substance currently known to the public as Ecstasy into ‘a serious, even patriotic drug’.

Although the idea of medical psychedelics has won a degree of acceptance from the public, the same cannot yet be said of psychiatry at large, or indeed of the patients who might stand to gain. Many of the small-scale studies carried out thus far have been on ‘normal’ volunteer subjects carefully screened for any history of mental illness or drug use. The first psilocybin trial, led by Roland Griffiths at Johns Hopkins University School of Medicine, recruited its subjects via small ads in the local Baltimore and Washington press under the heading ‘Interested in the Spiritual Life?’ This is a very different cohort from mental health service user groups and activists. These people tend to be sceptical of the current psychiatric model and are committed to exploring radical alternatives, yet – in my recent experience – they remain largely unpersuaded by the claims for psychedelic therapy. Many of them associate psychedelics primarily with psychosis and mental distress, and in any case they are more interested in social and mutual approaches that materially change their situation than in yet another wonder drug or six-session life-fix. Compare this with the medical cannabis movement, which has persisted in its loud demands for the legal right to use its medicine of choice, and whose grassroots and patient-to-patient networks have been crucial in assembling a mountain of evidence to make up for the silence of the medical profession.

Nor do there appear to be many psychiatrists, in the public sector at least, demanding the right to administer psychedelics to their patients. Most of the researchers making claims for their therapeutic potential are neuroscientists and psychopharmacologists without medical degrees. Psychiatrists in general practice operate with limited resources in a litigious environment: they would need to be sure of their cultural and legal footing before taking the risk of giving powerful mind-altering drugs to fragile and vulnerable patients. Within the pharmaceutical industry the development of new psychiatric drugs has ground to a virtual standstill, in part for the same reason. The reputation of Seroxat (paroxetine) was destroyed by the finding that it caused suicidal ideation in 0.3 per cent of depressed subjects; it is hard to imagine Big Pharma perceiving psychedelics as less risky than that, let alone investing the fortune ($2.6 billion on average) required to license drugs that wouldn’t even be eligible for patent at the end of it.

Psychiatrists and their patients are largely absent from the busy international milieu dedicated to the medicalisation of psychedelics. Among the drug researchers and cognitive psychologists in this community, the ethnobotanists and ethnomycologists, Jungian therapists and neo-shamans, the revolution is already palpable. Their narrative, as Michael Pollan summarises it, is that psychedelics ‘exploded’ in the West in the 1950s and showed enormous promise in early trials before, in the early 1960s, ‘the exuberance surrounding these new drugs gave way to moral panic.’ ‘Researchers watched in dismay’ as Timothy Leary and his ‘antics’ ‘ignited what would become a public bonfire of all their hard-won knowledge and experience’. By the 1970s psychedelics had been ‘outlawed and forced underground’; only over the last few years has cultural and scientific hostility dissipated to the point where their therapeutic potential can finally, and for the first time, be properly grasped.

The first clinical trials with a major psychedelic took place not in the 1950s but in 1895, in the medical department at what was then Columbian University, now George Washington University in Washington DC. James Mooney, an ethnographer at the Smithsonian, had acquired dried buttons of the mescaline-containing peyote cactus in Oklahoma from the Comanche chief Quanah Parker. The first experimental subject, a 27-year-old chemist, stretched out on the bed in his college room and experienced ‘a train of delightful visions such as no human being ever enjoyed under normal conditions … My pleasure so far passed the more ordinary realms of delight as to bring me to that high ecstatic state in which our exclamations of delight become involuntary.’ The second trial, on a 24-year-old reporter, could hardly have been more different. He developed ‘a feeling of great distrust and resentment’ towards the researchers, and ‘firmly believed that we were secretly laughing at his condition. He believed that we intended to kill him.’

It was clear even from these earliest beginnings that fitting psychedelics into standard models of pharmacology would be difficult. Most drugs have broadly the same effect on every subject. Even psychoactive drugs, where the vagaries of personality and mental state are in play, are broadly predictable in their effects: it isn’t the case, for example, that amphetamines are a stimulant for some people and a sedative for others. But with psychedelics, every dose seemed to elicit a different response. The third subject was poleaxed, unable to walk without assistance. The fourth noticed almost nothing. The fifth became obsessed with music, drumming time incessantly on a table. The researchers concluded that peyote held medical promise in cases of nervous disorders, melancholia and neurasthenia, but the trials went no further in this direction. For every positive experience there was a negative, and patients with nervous weaknesses were the ones most likely to find the drug distressing.

Mescaline was first synthesised in a Viennese laboratory in 1919. During the 1920s the neurologist Kurt Beringer led a research programme at Heidelberg in which it was administered to dozens of subjects, generating hundreds of pages of first-person reportage. Many of Beringer’s subjects were trainee psychiatrists; he encouraged them to spend time on the wards and interact with the patients during their trips, in the hope that their altered state would generate therapeutic empathy and insight. The programme ran for several years. It produced new theories of visual perception and led to some freewheeling artistic collaborations, but no practicable model for mental treatment. As the experiments ran their course, Beringer and his colleagues drifted away from their original aims and into phenomenology, existential psychology and psychoanalysis.

When Albert Hofmann synthesised LSD in 1938 and later accidentally ingested it, he recognised immediately that its effects matched those of mescaline and recalled that after Beringer’s ‘investigations failed to suggest any applications for mescaline in medicine, interest in this active substance soon waned’. But LSD – along with psilocybin, which Hofmann isolated from magic mushrooms in 1957 – caught researchers’ imaginations. With the biological turn in 1950s psychiatry and the discovery of antipsychotic compounds such as chlorpromazine (Thorazine in the US, Largactil in Europe), the new ‘hallucinogens’ were studied closely in the search for the causes of schizophrenia. However, the problems with administering them to patients were apparent from the start. Subjects who were given LSD and left alone in surgeries, in line with protocols that aimed to separate drug effects from other variables, often had terrifying experiences. From 1955 onwards it was administered to around 1500 US army volunteers; the official reports soft-pedalled the negative outcomes, which included nervous breakdowns, long-term psychotic effects and a fivefold rise in suicide rates.

The gradual decline in patient trials was accelerated by the Kefauver Harris Amendment to the US Federal Food, Drug and Cosmetic Act, introduced in 1962 after the thalidomide tragedy to tighten controls on pharmaceutical marketing. It stipulated that the efficacy of drugs be validated by randomised control trials against a placebo, that adverse reactions had to be reported to the US Food and Drug Administration, and that ‘quality’ in a pharmaceutical product was to be determined by the reproducibility of its effects. The impact on psychedelic research was severe. Much more data was required before human trials were permitted; the variability of patients’ responses made them, under the new definition, the very opposite of ‘quality’ drugs; and there were no biomarkers that could be used to measure their efficacy. Placebo trials presented a conundrum: a placebo with no psychoactive effect was recognised immediately, but if it had the same mental effects as the drug being tested, it was evidently not a placebo but the drug itself. Contrary to received wisdom, trials on psychedelics weren’t banned – research on psilocybin at the Spring Grove Clinic in Maryland, for example, continued with FDA approval until the late 1970s – but FDA approval for trials became harder to obtain, and their scope ever more tightly restricted.

At the root of what makes psychedelics so promising – or tantalising – to psychiatrists is, to use the term Michael Pollan takes from William James, their noetic quality. As James described this peculiar aspect of religious experience, ‘People feel they have been let in on a deep secret of the universe, and they cannot be shaken from that conviction.’ Psychedelic experience, too, has this quality, unlike other forms of chemically induced confusion or delirium. Subjects speak of ‘illuminations, revelations full of significance and importance’. Pollan captures this in his accounts of the experiments he has undertaken with LSD, magic mushrooms, ayahuasca and the DMT-containing secretions of the Sonoran desert toad. During a guided mushroom trip he asks his therapist if she can stop playing New Age ‘spa music’ and switch to Bach’s cello suite in D minor. The effect was shattering: ‘Even to call it “music” is to diminish what now began to flow, which was nothing less than the stream of human consciousness, something in which one might glean the very meaning of life and, if you could bear it, read life’s last chapter.’ As Pollan reads these words back later, ‘doubt returns in full force: “Fool, you were on drugs!”’ But ‘everything I experienced I experienced,’ and it remains indelible.

‘Curiosity,’ Pollan writes, ‘is an accurate but tepid word for what drove me.’ Apart from a couple of mild and mildly interesting mushroom trips in his youth, he had never sought to explore those mysterious states of consciousness which, in William James’s estimation, ‘forbid a premature closing of our accounts with reality’. Over the course of his researches and personal experiences he discovered that his hidebound middle-aged mind was more susceptible to change than he had thought possible. He now believes that ‘these remarkable molecules might be wasted on the young, that they may have more to offer us later in life, after the cement of our mental habits and everyday behaviours has set.’ What they have ‘to offer’, once leached of the emotional intensity with which it is delivered, may resemble ‘platitudes that wouldn’t seem out of place on a Hallmark card’, but it is no less powerful for that. ‘The mind is vaster,’ Pollan concludes, ‘and the world ever so much more alive, than I knew when I began.’

Lauren Slater​ , by contrast, is urgently seeking rescue from the psychopharmaceuticals currently available. Over the years since she wrote Prozac Diary (1998), antidepressants and antipsychotics have made it possible for her to recover from a childhood of abuse and to live a full adult life with a career and a family. But they have destroyed her physically: she suffers from aphasia and memory loss and is overweight, with diabetes and failing kidneys. ‘As the years close in on me,’ she writes, ‘my lifetime now seems seriously foreshortened, not because of a psychiatric illness but because of the drugs I have taken to treat it … at 54 years old, my body is in the shape of an octogenarian with issues.’ She comes to psychedelics wanting to find out if they can alter her mind sufficiently to release her from the drugs that are killing her.

Slater weaves her personal history into the origin stories of the 20th century’s revolutionary psychiatric medicines – chlorpromazine, lithium, imipramine, fluoxetine (Prozac) – and the current research into psilocybin and MDMA that she hopes will play a role in her future. Most of these mind-changing drugs were stumbled on by accident (chlorpromazine and imipramine in the hunt for antihistamines, LSD and MDMA in research on vasoconstrictors), then fitted into psychiatry after their psychotropic effects were recognised. All were initially hailed as wonder drugs, revolutions in mental treatment. Little has changed. The psychopharmacology of today, as in the 1950s, is characterised by ‘consistent confusion, a range of questionable cures, and then the occasional home run’. Yet within this history, psychedelics are a novel proposition. The claim is that their effectiveness depends not on a lifetime of daily maintenance, but on a handful of doses over a short period or even a single session: a major selling-point for prospective patients like Slater, though much less attractive to Big Pharma. Although the new science of psychedelics is heavily skewed towards neuroanatomy, particularly the use of imaging technologies to explore their effect on the brain, the promise of psychedelic medicine lies not so much in their biochemistry as in the subjective experience they generate: changing minds rather than changing brains.

Researchers in the 1950s quickly learned that people on psychedelics are highly susceptible to suggestion. This wasn’t lost on the CIA: much of the early research into LSD was on its potential use as a brainwashing agent. The pioneers of psychedelic therapy, such as Al Hubbard and Humphry Osmond, stressed the importance of what was later called ‘set and setting’: careful priming of the patient’s mindset, mood and expectations, and thoughtful attendance to their surroundings. They avoided sterile hospital rooms in favour of private sessions in congenial homes and gardens, with music playing in the background and art history books to leaf through (this was the scenario Osmond constructed for Aldous Huxley’s first mescaline trip, which he wrote about in The Doors of Perception). Oscar Janiger, private psychotherapist in the 1950s to Hollywood stars such as Cary Grant, claimed miraculous results with this approach, excavating buried memories and traumas, effectively condensing years of analysis into a few sessions. At $500 a session, the LSD provided free by Hofmann’s company Sandoz in return for case reports, the business model was miraculous too.

Guided therapy remains the template for psychedelic medicine today. It isn’t drug therapy in the usual sense, but involves the creation of a context in which the power of talking cures is enhanced. In this sense the push for medical acceptance of psychedelic treatment in the 21st century runs in the opposite direction to the drive for adoption of antipsychotics and antidepressants in the 1950s. The mind drugs of that era, as Slater relates, were heavily resisted by a psychiatric profession committed to Freudian and psychodynamic therapies, for whom the notion of ‘chemical cures’ was facile and reductive, not to mention tainted by their recent use in the German Reich. The significance of today’s attempt to medicalise psychedelics, though packaged in the language of brain imaging and receptor neurochemistry, is that it is predicated on shifting talk therapy from the margins of psychiatry back to its centre.

As Pollan writes, the contribution of Hubbard and his fellow pioneers was ‘to introduce the tried and true tools of shamanism, or at least a Westernised version of it’. This remains the goal of researchers such as the UCLA psychiatrist Charles Grob, who sees psychedelic therapy as a form of ‘applied mysticism’ that engages the ‘shamanic paradigm’ of orchestrating ‘extrapharmacological variables’. This expanded notion of medicine is hard to square with the FDA-mandated criteria of biomarkers, rating response scales and placebo-controlled trials. The psychedelic therapist’s ‘set and setting’ are the clinical researcher’s ‘expectancy effects’ and ‘confounding variables’. Yet there are useful parallels to be found in Western medicine: Cognitive Behavioural Therapy is beloved of policy-makers, after all, precisely because it promises to change minds, ingrained habits and behaviour in a few one-to-one sessions. Perhaps psychedelics could come to be thought of as an alternative to CBT. The use of psilocybin to treat death-related anxiety in patients with advanced cancer, which has shown great promise in the Johns Hopkins trials, is entirely compatible with the palliative care regimes developed in hospices outside the ambit of medicine. Addiction therapy with psychedelics has parallels with the use of hypnosis or neurolinguistic programming (both non-medical procedures performed by practitioners accredited by their own professional bodies) for the same purpose. Some researchers compare the effects of psilocybin or ketamine on depression to electroconvulsive treatment. In the absence of a clearly understood mechanism for either form of treatment, the effect of psychedelics is sometimes described in terms of the old ECT metaphor, ‘shaking the snow globe’; ‘whacking the TV set’, ‘defragging the hard drive’ or ‘pressing control-alt-delete’ are other possibilities. Maybe we shouldn’t consider psychedelics to be pharmaceuticals just because they happen to be chemicals.

But advocates of psychedelics aren’t aiming for alternative or complementary status. They want psychedelics to be classified as bona fide FDA-approved medicines. ‘My life’s goal,’ Rick Doblin tells Slater, ‘is to see the psychedelics made into prescription drugs.’ This goal is being pursued by a handful of organisations, including Doblin’s MAPS, which is mostly funded not by academic or public health grants but by private donors and projects such as the Pineapple Fund, set up by bitcoin multimillionnaires. The hurdles to clinical acceptance are even higher today than they were in the 1960s, but MAPS and others are working doggedly through the FDA-mandated trial phases. Pollan closes his book with an account of a conference in Oakland last year organised by MAPS, at which Tom Insel, who headed the US National Institute of Mental Health until 2015, advised that the language of revolution should be carefully modulated: not ‘we’re gonna give psychedelics’ to patients, but ‘psychedelic-assisted therapy’.

Even this hybrid proposal would be, as Pollan notes, ‘a very large pill for modern medicine to swallow’. Insel’s suggestion is along the same lines as Slater’s: ‘Psychiatry must take a step back from its neurological love affair’ and embrace practices beyond the pharmacy that are currently relegated to the status of placebos. Slater contrasts this with the future envisaged by the likes of Jeffrey Lieberman, former president of the American Psychiatric Association: ‘a psychiatry hitched to PET scans and fMRIs’ in which mental distress is located ever more precisely in the brain and treatment embraces new technologies such as electrostimulation and neural implants.

Pollan​ frequently recalls a phrase he heard from Bob Jesse, Roland Griffiths’s collaborator at Johns Hopkins: ‘the betterment of well people’. His mind has been changed and his life enriched, but he wasn’t suffering from mental illness when he undertook his experiments with psychedelics. What would be available to him, and millions like him, in a future world of medicalised psychedelics? Who would get to trip, and who would decide? There are many alternative approaches to ‘drugs that change our minds’. They could be treated as tools of spiritual or personal growth, like yoga or meditation; as a means of temporary escape from life’s routine, like a festival or a holiday; as an enhancer of other sources of wellbeing, such as creative work or immersion in nature; or indeed as self-medication without professional involvement.

Nobody at the MAPS conference wants to have this conversation. Insel advised that ‘psychedelics would probably need to be rebranded in the public mind and it would be essential to steer clear of anything that smacked of “recreational use”.’ Roland Griffiths, pressed on Bob Jesse’s interest in the betterment of well people, ‘seemed to squirm a bit in his chair’ before answering: ‘Culturally right now, that is a dangerous idea to promote.’ Charles Grob advocates the shamanic paradigm but stresses: ‘We don’t want to be associated with flower power. We want to be seen as serious scientists.’ It appears that if psychedelics are to become medicines, all their other uses must be deemed ‘recreational’, unscientific and unserious.

Twenty years ago it was assumed that campaigning for the medical use of cannabis was the most promising route to making it legally available. Now that non-medical regulated markets are up and running, the same route is in principle open to psychedelics, and a proposition for the licensed non-medical sale of psilocybin is headed for the California ballot in 2020. In Europe, you can already – discreetly but perfectly legally – travel to Amsterdam to buy psilocybin truffles, the form in which magic mushrooms are sold over the counter in coffee shops. Grassroots initiatives such as Spain’s cannabis social clubs, several hundred of which now operate with the tolerance of local police forces, offer an alternative to medical prescription.

Medicalising psychedelics, by contrast, forces a choice between the betterment of the well and the treatment of mental illness, and it isn’t at all clear what the latter would amount to. The calculus of risk and reward suggests that the psychiatrists who offer psychedelics would gravitate towards wealthier clients with less serious conditions. Something similar is already underway in the US with ketamine, which, unlike LSD, psilocybin and MDMA, isn’t prohibited for medical use and can be prescribed for psychiatric conditions (but isn’t covered by medical insurance). Therapists in California offer a dose of ketamine, with or without accompanying therapy, for anything between $500 and $1000, for a dose that costs the clinicians around $2.

The contrast between Pollan’s and Slater’s experiences suggests that whatever criteria finally emerge for entitlement to a prescription, medical need is unlikely to be first among them. Pollan finds his way into a colourful network of clandestine practitioners who offer him, along with a smorgasbord of psychedelics, a spectrum of therapies from guided meditation to depth psychiatry to neo-shamanic healing. Slater, by contrast, asks Rick Doblin if he would consider allowing her to try MDMA, but when he hears that she’s also taking Effexor for depression, he says: ‘You can’t take MDMA with an SSRI.’ She gets the same response from an underground psilocybin therapist when she discloses her psychiatric history, including stays in residential hospitals: ‘It won’t work for you.’ She never does get her trip. One of Pollan’s prospective guides, a Romanian LSD therapist, told him about a session with a troubled client who sued him after he subsequently had a breakdown. After that ‘I decided, I don’t work with crazies anymore. And as soon as I made this statement to the universe, they stopped coming.’ These days he treats Silicon Valley entrepreneurs.