In late 2016, Robin Carhart-Harris had a morbid IDEA. The head of psychedelic research at Imperial College London and his lab were about to embark on a study of dimethyltryptamine (DMT). The compound is more commonly ingested in the form of ayahuasca, a psychoactive brew boiled from the Banisteriopsis caapi vine and Psychotria viridis, or chacruna, leaves. It has been used for centuries by indigenous cultures in Latin America to communicate with the spirit world and, more recently, by millennials on voyages of self-discovery. People who take ayahuasca report of mental journeys to other realms. Many have visits from unearthly entities. Experiences like these are also described by those who come close to death. So Carhart-Harris set out to discover whether psychedelics in general, but especially DMT, induce a state in the brain that is similar to the act of dying.
I meet Carhart-Harris at his office in Hammersmith, west London. Out of the window, muddy playing fields stretch beneath a midwinter sky. The conversation is suitably gloomy but, in a way, it is typical of the research fellow, who can be pensive and grandiose.
Scanning the brain of a volunteer who is tripping on DMT is not a simple procedure, Carhart-Harris tells me. Electroencephalogram (EEG) caps are full of sensors that are disturbed by the slightest movement.
Participants are blindfolded. A minute or so after the drug is injected, they begin to hallucinate vivid geometric patterns that bloom in texture and scale. Every minute, the researchers ask the participants to rate the intensity of their experience from nought to ten. In Carhart-Harris’s previous studies of LSD and psilocybin, the psychoactive compound found in magic mushrooms, the peak would be around seven.
“For volunteers, there seems to be some kind of threshold at which there’s almost a pop,” – he snaps his fingers – “into this DMT world.” On the EEG monitor the researchers can see when the threshold had been crossed. The peaks and troughs of the oscillating traces of the reading usually become shallow, indicating that a lot was happening.
While under the influence of DMT, participants do not always hear the researcher’s questions. “I was in this place that was unbelievably bright and full of unconditional love,” one subject tells me. “And when I was coming back to my body it was more blue, purple and dark. Then I saw this being, this insect-like being that was female, and she opened her arms and then her tongue came out of her mouth and she entered me.”
It takes participants about 15 minutes to fully return to their normal selves. Afterwards, they are asked to describe their experience using a questionnaire: Did you feel separated from your physical body? Did you feel a sense of harmony with the Universe? Of course, the ratings were subjective, one of the limits of psychology. Yet when the answers were tallied and compared to those of people who had been through a near-death experience, there was little statistical difference.
Carhart-Harris was not surprised with the results. He has long suspected that psychedelics induce some kind of mind death that mimics an aspect of the death process itself. He felt that the measure was useful because it revealed something about the nature of the drugs in their ability to give users a new way of thinking. Similarly, people who have had a near-death experience will say that they are able to see the world afresh.
For half a century, researchers interested in psychedelic drugs have inhabited the fringes of neuroscience. In the UK, Carhart-Harris is responsible for making this field of study respectable again. He has spent much of the past decade investigating the ways certain compounds give rise to uncommon conscious states. He thinks that Lysergic acid diethylamide (LSD), psilocybin and DMT are powerful tools for accessing the brain. “The term ‘psychedelics’ comes from Greek words for ‘mind-revealing’ – and that’s what these drugs do,” Carhart-Harris says.
“The question is, what is dying? I guess a major part of the death process is that the thing at the top of the hierarchy, if you like, that tends to dominate consciousness ordinarily when you’re awake, is the first thing to go. That’s why DMT is useful. You can appeal to the lessons that are there when you understand that your ego isn’t absolute. That’s an amazing insight, and it can be a really healthy insight. It can allow you put things in perspective.”
He also believes that psychedelics could potentially be used for treating mental illness. Current treatments for depression, anxiety and addiction can be life-saving, but they also have limits. About a third of people treated for depression never fully recover.
In England, antidepressant prescriptions have doubled in the last decade: one in every 11 UK adults is prescribed them. Psychedelics, Carhart-Harris thinks, could be used to deliver a turbo-charged form of therapy, one that does everything that psychoanalysis does, but in a more cost-effective manner.
Robin carhart-Harris is not the first scientist to think that psychedelic drugs could be used to treat psychiatric disorders. Albert Hofmann, the Swiss chemist who first synthesised LSD in 1938, referred to his discovery as “medicine for the soul”. In the 50s and 60s, tens of thousands of patients were given psychedelics for disorders such as anxiety and addiction. A 2016 meta-analysis of 19 studies published between 1949 and 1972 found that 79 per cent of patients showed “clinically judged improvement” after treatment. But the heyday would be short-lived: in 1971, LSD was made illegal thanks to the United Nation’s Convention on Psychotropic Substances treaty, ending all major research programmes.
Carhart-Harris, who is 37, entered the field just as the disapprobation of drugs was waning. In 2006, a study by Francisco Moreno at the University of Arizona, Tucson, found that psilocybin reduced the symptoms of obsessive-compulsive disorder in nine patients. Then, in 2011, another study found that the same alkaloid significantly eased the anxiety of people dying of cancer. Each year, there are progressively more clinical trials with psychedelics. In 2016, three investigated the therapeutic action of psilocybin; another looked at ayahuasca.
Brain imaging has also transformed neuroscience. The development of functional magnetic resonance imaging (fMRI) means it’s now possible to observe the brain thinking, doing and feeling. Scientists in the 60s “second wave” of psychedelic research – the first being the use in indigenous cultures – could only guess at the biological mechanisms by which the drugs change the brain. Carhart-Harris uses imaging to unpack their mysterious power.
The offices of the Psychedelic Research Group are on the fifth floor of Imperial’s Burlington Danes building. There, on Thursdays, Carhart-Harris holds a team meeting. On the day I attend, he has just returned from Peru where he had been invited to carry out a brain scan on a participant in a traditional shaman-led ayahuasca ceremony.
In person, Carhart-Harris is polite and warm. He is medium height and athletic, with just-greying hair and electric-blue eyes. His humour runs on the dry side. “I’ve just come back from a retreat in the Amazon,” he tells the group. “It’s now very clear to me that the spirits are real and science is a waste of time.”
In his office is a framed poster, bought at the Sigmund Freud Museum in Vienna, containing the quote: “It is not easy to deal scientifically with feelings.” On shelves above his desk, behind a bottle of mouthwash and a disposable razor, are Freud’s complete psychological works. “I have something quite frightening,” he says, reaching for an A3 pad on the top shelf. Text copied from Freud’s books, referenced and colour-coded, filled every sheet. On a page entitled “The Ego”, one phrase – “WITH THIS IDENTITY IS ATTAINED” – is capitalised and highlighted.
Carhart-Harris has a reputation in the department for excessive indexing. “At one point he asked if I could borrow a book from the library for him,” David Erritzoe, a psychiatrist and research fellow, tells me. “I said, ‘OK, but why can’t you go yourself?’ He was like: ‘It’s a bit problematic.’” Carhart-Harris had been banned for highlighting and scribbling in the library’s books. The ban remains in place today.
As a scientist, Carhart-Harris has two overarching and interlacing concerns: he wants to understand how psychedelic drugs act on the brain in order to so dramatically alter thought, mood and behaviour; and he wants to see if their power can be harnessed to serve humankind.
A few years ago, he undertook a study to see if psilocybin could be used to treat depression. He enlisted 20 people who had tried at least two courses of medication, so called treatment-resistant depressives. On average they had lived with the disorder for 17.7 years. On dosing day, each patient would arrive at Imperial at 9am. After answering a questionnaire in the patient lounge and taking a urine test, they were led to a room that had been decorated to look more like a bedroom than a clinic, with drapes, flowers, music playing and electric lights that flickered like candles. After swallowing the psilocybin capsule, the patients were invited to stretch out on a bed. Two psychiatrists stayed in the room – Carhart-Harris believes that a soothing environment and psychological support before, during and after dosage is essential. People on psychedelics are psychically vulnerable; anxiety and paranoia are not uncommon.
When the results came in, they showed that the depression had reduced in all of the patients. (The results reflect the experiences of 19 people; one dropped out.) Three weeks after dosage, nine were in remission; after five weeks, all but one felt less depressed.
Carhart-Harris admits the study has its problems: it was not placebo-controlled and because of the small sample size it is not possible to make grand inferences. Yet for some of the participants, the treatment was life changing. “Before, I was like a beetle on its back, now I am on my feet again,” reported one. Another went out for dinner with his wife for the first time in six years, feeling “like a couple of teenagers”.
The second of three brothers, Carhart-Harris was born near Durham in northeast England. When he was four, his family moved to Poole on the south coast. He was raised Catholic, and though he is now an atheist, traces of the altar boy remain. Psychedelics, he says, were suppressed during the 60s like a “forbidden fruit” of which knowledge was too dangerous.
In his youth, Carhart-Harris was not academic. He liked PE and science, but would hide his school reports. “I remember one that started, ‘Robin’s behaviour gives cause for concern as he progresses into his GCSE years’,” he says. “I was a bit of a precocious raver.” He was also hobbled by anxiety. Once, when asked to read aloud to his classmates, he found he couldn’t breathe. He went to the University of Kent to study biochemistry but dropped out. He returned home and applied to his local university to study psychology. “I wrote this personal statement – you know what young people are like sometimes, grand and over the top – I was saying how I wanted to help people to just live and not be shackled by mental-health problems.”
Carhart-Harris first encountered Freud in 2004, during his masters at Brunel University London. At a seminar on “methods to access the unconscious mind”, he discovered that Freud’s theories rest on a belief that the mind is like an iceberg, with the majority of its mass hidden from the view of the conscious self, which he called the “ego”. He was captivated by Freud’s ideas but saw that there was no empirical evidence to support them. “I thought, what is this cult if all it is is us believing?” Born in an age before computers and brain imaging, Freud had relied on blips in the system, be it slips of the tongue, compulsive patterns of behaviour or dreams. Carhart-Harris was amazed that these were still the methods espoused by his professor. Dream interpretation just seemed too kooky.
Back in his room, he typed “LSD unconscious mind” into the library search engine. It returned a title from 1975, “Realms of the Human Unconscious: Observations from LSD Research” by Stanislav Grof. He took out the book and read it that same day. Something clicked: “I was like: this is fucking big. You can prove something really fundamental about the mind.”
Freud had said that dreaming was the “royal road” to the unconscious. Carhart-Harris felt sure the same was true of psychedelics. He began to wonder: how is the ego represented in the brain? What are the neural correlates? He felt that the obvious place to start was with a scan of someone’s brain on LSD. He looked for a lab where such a thing might be possible.
Carhart-Harris wrote to David Nutt, then the head of the psychopharmacology unit at Bristol University. (Nutt has since moved to Imperial.) Nutt was interested in brain circuitry and addiction and was publicly critical of drugs policy; in 2007 he lost his place on the Advisory Council on the Misuse of Drugs, a body that advises the government, over outspoken remarks. He agreed to meet.
“I went along, nervous as hell,” Carhart-Harris said. “I told him ‘I want to study the brain on LSD, I think it could tell us a lot about Freudian principles and their biology.’” Nutt heard him out, but rejected his proposal. Then he asked if Carhart-Harris was interested in MDMA. The department was in need of a PhD student to investigate whether the drug damages the brain’s serotonin systems. Carhart-Harris said that he was interested but left feeling despondent. On the way home he called his mother. She advised him to accept the offer, that it could act as a stepping stone.
The study of neurons to try to understand how consciousness arises is a waste of time, says Carhart-Harris. All experiences – from the disgust of seeing a dead rat to the memory of a childhood holiday – happen as diverse parts of the brain become networked. In an fMRI scan, electromagnets detect changes to blood flow in the brain. Since neural activity increases blood flow, it is possible to observe discrete parts of the brain reacting to various stimuli; on screen, engorged regions are presented as colourful splotches. Zoom in too closely and the full picture is lost. “It’s not thinking about the quarks or atoms in the neurons,” Carhart-Harris said. “That’s kind of meaningless, there are too many steps and levels to get up to a point at which you have a functioning system that maps on to something that you can feel.”
Normally the brain is good at hiding its vast and unfathomably complex machinations. Most mental activity is not under conscious control, and we only notice the fact if we make a Freudian slip or pause to consider a pupil dilating. One barrier between the self and the vast data-processing thought-swamp of the rest of the brain is what neuroscientists call the “default-mode network”. It is an intricate system of interlinking brain regions that together give rise to what some call the “monkey mind” – the stream of internal chatter that surfaces in between periods of more focused thought.
By studying LSD, Carhart-Harris has found that psychedelics do something unusual to the default-mode network. In a 2016 study published in the Proceedings of the National Academy of Sciences journal, he injected 20 healthy volunteers with either 75 micrograms of LSD or saline, a placebo, on two separate occasions. As the drugs kicked in, volunteers reported a “sense of eerie dread” as their anchorage in the world shifted. “Usually, depending on how it goes, there’s a bit of a kick back, there’s some anxiety.” They then had two fMRI scans followed by a magnetoencephalography (MEG) scan – if the various scans pointed to the same mechanisms the results would be stronger. Afterwards, volunteers responded to a questionnaire so that scan data could be correlated with experience. Statements included “sounds influenced things I saw” and “edges appeared warped”.
In the brains of the volunteers, as the visual network became more connected (all the LSD-injesting participants hallucinated), the blood flow in the default-mode network receded, indicating that it had lost its force. For the participants, this correlated with a change in the way they processed the world. The monkey mind had gone quiet.
In society we talk approvingly of “well-rounded” individuals and “getting ourselves together”. But a little chaos can be a good thing. In certain psychiatric disorders, the brain becomes entrenched in pattern. Someone with depression might have relentlessly negative thoughts about themselves; people with obessive-compulsive disorder get trapped in repetitive action.
Carhart-Harris believes that psychedelics work like a reset button. He likes the analogy of shaking a snow globe. Under LSD, as the default-mode network disbanded, other segregated parts of the volunteers’ brains began communicating in an unpredictable way – a state of increased entropy. Psychedelics seem to break down entrenched ways of thinking by dismantling the patterns of activity on which they rest.
For instance, the most-prescribed class of antidepressants, selective serotonin reuptake inhibitors (SSRIs), raise levels of serotonin in the brain by blocking its natural reabsorption. When we are anxious or stressed, parts of the brain become overactive. Serotonin, a neurotransmitter, binds to receptors in the brain that are prevalent in regions involved in stress and emotion, the 5-HT1A receptors. Once bound to the receptor, serotonin initiates a signal that decreases the activity of the neurons. By keeping the 5-HT1A receptors doused in serotonin for longer than normal, SSRIs calm the stress circuitry. But they also blunt emotion more generally.
Psychedelics work on the brain rather differently. Though they also temper serotonin, they target the 5-HT2A receptors, concentrated in the cortex. Humans have vastly more cortex than other species, and the 2A receptors are dense in regions with human-specific traits such as introspection, reflection, mental time travel and the self itself.
Carhart-Harris thinks that when psychedelics disrupt the level of connectedness in the cortex they create space for insight and catharsis. For patients, the process can be difficult. “You need to be able to say to people: this could be tough, it could at times be the worst experience of your life and you may see your worst fears staring at you in the face.” But he believes that the process can be freeing. “I think it’s possible to know your defences and know your insecurities and through knowing them not be at the mercy of their force.”
In July 2017, Carhart-Harris gave a talk at a conference called Breaking Convention, which bills itself as “the largest psychedelic conference in the known Universe”. Held at the University of Greenwich, the gathering was good-natured, with a propensity for tie-dye. The programme listed 150 speakers from across the psychedelics spectrum. One talk was on the nascent field of phenomenoconnectomics, a largely theoretical method of quantifying altered states. Another was titled “Encounter with the Jaguar”.
Carhart-Harris stuck around for most of the conference, fielding entreaties from undergraduates, hobnobbing and catching a few science talks. He attended a lecture called “Mental Organs and the Depth and Breadth of Consciousness” by Thomas Ray, a biologist at the University of Oklahoma. As talks on consciousness go, it was difficult to follow, whipping through molecular compounds, the evolutionary tiers of the mind and the “rise of insanity”. When Ray presented his central idea, that “conscious space” is modulated by the brain’s 5-HT7 receptors, Carhart-Harris sat forward. “These are wild extrapolations,” he whispered.
In the question-and-answer session, Carhart-Harris’s hand shot up. “Have you plotted the correlation between the affinity of psychedelics for the 5-HT7 receptor and the drug’s potency?” Ray said that he had not. “I think that you should, it’s important.” People fidgeted: this was not a hostile crowd.
Afterwards, Carhart-Harris left the conference and stopped in a local café for lunch. He was quiet, almost ruminative. “How can you present such poor science? I think that people should be allowed to speculate. But the people who contribute to the mainstream perception that this research is pseudo-scientific undermine the field.”
The episode had tapped into something deeper. Research with drugs that are strictly controlled by the law is not straightforward. In the UK, LSD is a class A, schedule 1 drug. Heroin, which causes more harm to individuals and society than LSD, and is addictive, is in the slightly less prohibitive schedule 2 because it is a diamorphine, which can be used for medication. For a lab to stock LSD it must acquire a licence from the Home Office and meet certain criteria, such as having a fridge that is bolted to the wall. All this is demoralising. It took Carhart-Harris three years to execute the psilocybin-depression pilot.
Funding is also an issue. Big pharmaceutical firms are generally not inclined to back research into drugs that are illegal and un-patentable. Carhart-Harris’s studies have been largely financed by grants, donations and crowdfunding. In 2016, he applied to the Wellcome Trust, the largest charitable supporter of science in the UK. When he was shortlisted, he thought he stood a chance. He had meticulously designed the two trials he was hoping to carry out if he got the £1 million-plus grant. But one of the judges on the panel took issue with his suggestion that “well-being” should be a primary outcome. Carhart-Harris had the impression that the judge considered it flowery. He didn’t get the grant.
“I’ve got a feeling they’re always thinking: he’s a hippie,” he tells me at lunch. “And when something comes out of your mouth like: ‘I want to measure well-being’, they are like: I knew it! He’s a hippie, he’s not a real scientist.” Carhart-Harris went back to the trust, asking them to be honest: was it the area he was researching? But when they said it wasn’t, he didn’t believe them.
Later that evening, at the conference soirée, Carhart-Harris gets talking to the organisers of a Finland-based conference on psychedelics at which he is scheduled to speak. What, they want to know, does he think of ketamine? A study at the University of Oxford has found that some patients with treatment-resistant depression responded positively to the drug. Carhart-Harris tells them that the work is interesting, but he does not think ketamine is as important as psilocybin.
Of all the psychedelic drugs, Carhart-Harris believes that psilocybin is probably the closest to becoming legal. It has fewer stigmas attached to it, and in the brain, LSD is active for far longer, making it less practical in the clinic, while DMT is probably too powerful. The fact that psilocybin occurs naturally in mushrooms also helps. It could be marketed as a natural alternative to antidepressants. He believes that, one day, psychedelic therapy will be available on the NHS, just like SSRIs and cognitive behavioural therapy are today.
This spring, he plans to do another psilocybin study, this time directly pitching psychedelics against SSRIs. Fifty people living with depression will receive either daily doses of escitalopram, an antidepressant, or a single 25mg shot of psilocybin, plus therapy. The contest is unequal, in one sense, because those taking escitalopram will have a regular reminder that they are taking medication. “Maybe psilocybin will work at least as well, that’s my prediction,” Carhart-Harris says. “But imagine that psilocybin is more effective? That’s really quite…” he tails off. “That would be something.”
Nicola Davison (@nicola_davison) is a freelance writer based in London
This article was originally published by WIRED UK
