The Daily Telegraph - Saturday - The Telegraph Magazine
Can magic mushrooms cure depression?
Mick Brown investigates
Along a nondescript corridor, in a nondescript block at a hospital in west London, a door opens to a rather surprising room. A single bed, scattered with colourful cushions, stands in its centre, enclosed by screens decorated with images of a forest. Lamps in the shapes of rocks bathe the room in a comforting glow; soothing music percolates from hidden speakers.
Over the past few months, at regular intervals, volunteers suffering from chronic depression have been entering the room and, after a preliminary, reassuring talk with a guide, been given a dose of the psychedelic drug psilocybin. They have been invited to lie down, put on an eye mask and relax. After an hour or so they will have begun to experience the first effects of the drug – colours and patterns rising and falling, the sense of their body in space beginning to change. They will likely have experienced feelings of euphoria, of their ‘self ’ being immersed in
and conjoined with something deeper and universal. In some cases, they might have experienced quite the opposite – feelings of disorientation and fear.
Some five hours later they will have felt sufficiently restored to their normal selves to leave, knowing that a few days later they would be repeating the episode.
The trials at Hammersmith Hospital are being conducted by the world’s first centre for psychedelic research, at Imperial College London. Early indications are that psilocybin, the hallucinogenic compound found in magic mushrooms, may be the magic bullet for one of the most pressing global health crises of our times.
About a fifth of women in the UK and a sixth of men show symptoms of anxiety or depression. According to the World Health Organization, more than 300 million people globally suffer from depression, and it is the leading cause of disability worldwide.
Nor has there been any significant progress in treatment in the past 30 years.
The most common approach is selective serotonin reuptake inhibitors (SSRIS) such as Prozac and Zoloft, which were developed in the 1980s. In England, the number of antidepressant prescriptions has doubled in the past decade, with almost 71 million handed out in 2018, compared with 36 million in 2008.
‘Psychedelic’ is a term freighted with associations, not all of them positive. It conjures up the 1960s, psychedelic music, tie-dye T-shirts, summers of love, happy – and possibly unhappy – hours in the Healing Field at Glastonbury. It does not conjure up images of rigorous scientific testing, with a view to the application of psychedelics as a treatment for a range of mental-health conditions – but that was the purpose for which, in the West at least, they were initially intended. Psilocybin was first isolated in the late 1950s, by a chemist working for Sandoz Laboratories in Switzerland named Albert Hofmann – the same man who 20 years earlier, in search of a respiratory and circulatory stimulant, gave the world LSD.
Sandoz initially made LSD and psilocybin available on a limited basis for clinical and research purposes, and by the early 1960s a handful of psychiatrists in America had begun tentatively using the drugs in the treatment of anxiety states and obsessional neuroses. The actor Cary Grant famously took more than 50 LSD trips under the guidance of his California therapist, declaring that as a consequence he could no longer behave untruthfully to anyone, ‘and certainly not to myself ’. As a further incentive to anyone minded to try it, Grant added, ‘Young women have never before been so attracted to me.’ Bill Wilson, a co-founder of Alcoholics Anonymous, also took LSD under guidance and was convinced
the drug could provide the spiritual awakening to help alcoholics get sober.
According to Michael Pollan, author of
the bestselling How To Change Your Mind: What the New Science of Psychedelics Teaches Us about Consciousness, Dying, Addiction,
Depression, and Transcendence, between 1950 and 1965 there were more than 1,000 peer-reviewed studies into the therapeutic benefits of psychedelics published, and six international conferences on LSD. ‘It was mainstream research.’
It was early investigations into LSD that began the line of research leading to the discovery of serotonin receptors, and eventually to SSRIS.
But in the 1960s, the genie escaped from the bottle, with psychologist and LSD guru Timothy Leary’s fervent proselytising for psychedelics as the new religion, using the mantra, ‘Turn on, tune in, drop out.’ Newspaper stories about ‘wonder drugs’ gave way to lurid accounts of ‘ bad trips’ and – a favourite trope – people hurling themselves off buildings in the belief they could fly. LSD was outlawed in Britain in 1966, and America in 1968. (In the US psilocybin was outlawed two years later.) Sandoz withdrew both drugs from the market, in the process shutting down more than 70 research programmes in existence at the time. Psychedelic studies were banished to the outer darkness, regarded as fringe and potentially career-breaking.
‘Researchers became almost embarrassed to study it,’ Pollan says.
In recent years, however, the wheel has turned full circle. In 2006, a University of Arizona study into the effects of psilocybin on nine patients diagnosed with obsessivecompulsive disorder showed ‘significant reductions’ in symptoms – with more than half the subjects describing the experience as both mentally and spiritually enriching. Further studies at New York University and Johns Hopkins Hospital in Baltimore have shown impressive results, using psilocybin to alleviate depression in patients with lifethreatening cancer.
The team behind Imperial’s Centre for Psychedelic Research conducted their first trial in 2014, publishing the results in 2016. It was comprised of 20 people, between the ages of 27 and 64, who had been experiencing treatment-resistant depression for an average of 18 years – people who, as Dr Robin Carhart-harris, head of the centre, puts it, had ‘thrown the kitchen sink at their depression with drugs and psychotherapy’, with little success. Following treatment extending over one month, more than half of the group were in remission three weeks after the conclusion of the trial. ‘That was quite a breakthrough,’ Carhart-harris says.
Some are still depression-free, several years later. Some relapsed after three months, some at six months. ‘It is typical for the window of relief to last for a few months in people with histories of depression,’ Carhart-harris says, ‘after which another treatment session might be indicated. That’s something we need to do further research on.’
The centre is now engaged in a new round of trials that will run until next May. The sessions are a carefully structured mixture of drug and psychotherapy. Participants (all of them volunteers) are screened for eligibility and given a baseline brain scan and sessions of psychotherapy before being administered the first dose of psilocybin. They are then seen the following day to talk through the experience, and given another full day of therapy before a second dosing session. Three weeks after that the results are assessed against those of a control group being administered the SSRI escitalopram.
Both psilocybin and SSRIS work by modulating serotonin, but in quite different ways. Serotonin is used to transmit messages between nerve cells, and is thought to play a key role in maintaining mood balance.
‘SSRIS, in very broad terms, generally increase serotonin,’ Carhart-harris explains. ‘That’s good in situations of crisis, high stress, high anxiety, aggressive negativity – it just takes some of the weight off. Psychedelics are more of an emotional release – a catharsis.’
‘Psychedelics seem really effective in forms of mental illness characterised by being stuck in habits of thinking and behaviour that are destructive, that people can’t get out of: “I’m unworthy,” “No one can love me,” “I can’t get through the day without a drink,”’ Michael Pollan says. ‘We get into these grooves and we just can’t slip out of it.
‘What the psychedelics appear to do is undermine or relax those beliefs and allow new beliefs to come in. And by shaking the system – shaking the snow globe – things resettle in a different way. Another metaphor people have used is rebooting your computer.’
Neuroscientists have speculated that psilocybin and other psychedelics work on what is known as the ‘default mode network’ (DMN) – the part of the brain where our minds go to ruminate, reflect on ourselves and others, and worry. The DMN is thought
‘Psychedelics shake the system… another metaphor is rebooting your computer’
to play a critical role in the creation of mental constructs or projections, the most important of which is the construct we call the self, or ego. Psychedelics appear to temporarily override the DMN, causing the usual boundaries we experience between the self and the world, subject and object, to melt away, giving rise to a sense of communion with the universe, which some construe as a mystical or religious experience.
For some people it can lead into what Carhart-harris describes as ‘a dark place’. The guide, who remains in the room at all times, is there to provide ‘a protocol of reassurance’ if someone becomes unhappy.
In clinical terms, ‘psychedelic therapy’ – for want of a better phrase – appears to offer considerable advantages to conventional treatments. SSRIS can, to all intents and purposes, cause dependency; people can’t get off them easily, and they may have adverse side effects that include nausea, headaches and sexual dysfunction. Psilocybin is neither toxic nor addictive, and there is no known lethal dose.
‘There are a lot of question marks over SSRIS,’ Carhart-harris says. ‘They’re palliative, not curative. If we were being really bold we could say psilocybin is curative. Potentially so. The data may be pointing in that direction.’
The mounting clinical research into the possible benefits of psychedelics has been mirrored by the growing practice of what is known as ‘microdosing’: self-administering small amounts – roughly one-tenth of the ‘trip’ dose – for either therapeutic reasons, or as what Pollan describes as ‘a mental vitamin’, to help focus and enhance creative insights. In the UK both LSD and magic mushrooms are illegal Class A drugs carrying a maximum sentence of seven years in prison for possession.
The practice started around 10 years ago, with a methodology devised by an American psychologist and psychedelics researcher named James Fadiman, and caught on in Silicon Valley as a ‘productivity hack’. But it has since made the journey from the campuses of tech companies to the discussion pages of Mumsnet, as a suggested salve for depression and anxiety.
Laura Nys (not her real name), who works as a freelance graphic designer, had suffered from anxiety and depression for most of her life. As a teenager she was prescribed antidepressants, but ‘that wasn’t giving me any space to understand what the underlying problems were’. She later spent time in therapy. ‘That helped a lot,’ she says, ‘but there were still things I couldn’t shift.’
After reading about microdosing online, Nys acquired a supply of magic mushrooms from a friend of a friend. For her first experience, she made the mistake of taking ‘a massive dose’, alone. ‘I don’t think I was prepared for what happened. It was like watching myself die. I thought, this is interesting; a bit of me is gone, what happens now? And suddenly I was a baby again, reliving my entire emotional life in sequence. It was absolutely horrible.’
Undeterred, she began to take the advised dose found online (measured on a set of jeweller’s scales) every third day, over a period of a month.
The effect of the drug in such a small quantity was almost sub-perceptual, and she was able to go about her daily life quite normally, but the impact on her mood was striking. ‘I felt a massive reduction in anxiety. And, perceptually, just an appreciation for the world around you, nature – the moment basically; just feeling more in harmony and engaged with things. I was much less closed off with other people. I’d never thought of myself as a closed-off person, but there was a noticeable difference.’
The downside came when, after a few months, she looked at her bank statement. ‘I realised I hadn’t been chasing down work so much – because I’d felt so contented. When you work for yourself you do need a degree
A treatment requiring two doses presents a challenge to the drug industry
of anxiety to keep the wheel turning. That was the point where I stopped.’
Nonetheless, she says, the overall experience has been beneficial. ‘I’d taken tranquilisers as an adult for anxiety. During that period I didn’t touch them. My anxiety levels are creeping back, but now I feel I can take a step back and say, this feels very real, but it’s actually a very subjective feeling that I’ve constructed. There’s the realisation that things pass.’
Carhart-harris is sceptical about the efficacy of microdosing. ‘We’re lacking any real data as to how reliable and safe it is. It might be a good thing when conditions are good, but not be such a good thing when things get difficult and complex.
‘What I think we have with psychedelic therapy is a really exciting hybrid model that borrows from biomedicine, what we know about the brain, and from psychotherapy. Marry them together and you’ve got something that’s much better than drugs and much better than therapy. Microdosing isn’t that, because it doesn’t do the psychotherapy.’
He believes that psilocybin may have potential for addressing a range of mentalhealth problems. The centre is planning trials on the treatment of anorexia next year, and seeking volunteers.
‘Addictions are on the radar,’ he says. ‘Obsessive-compulsive disorder, and things like chronic pain – even obesity. But there has to be a good, rational reason why we should be thinking of the application of psilocybin to these things, otherwise it looks like we’re getting carried away and regarding it as some kind of panacea, which would be wrong.’
The pharmaceutical industry is watching the progress with cautious interest. A treatment that requires only two doses to effect a long-term change in a patient’s personality and outlook presents an interesting challenge to an industry manufacturing drugs that require daily usage over a period of months, or years. But there is one Uk-based company working on devising a model of treatment that could well become commonplace in the future.
Compass Pathways was founded in 2016 by George Goldsmith, an American entrepreneur with experience in pharmaceutical regulation, and his wife Ekaterina Malievskaia, a physician and clinical researcher. Their interest in psilocybin research was prompted by the plight of their son, who suffered from acute depression and obsessivecompulsive disorder that no amount of therapy or drugs had been able to alleviate.
‘There has been a lot of quality research,’ Goldsmith says. ‘But what’s been missing is any clear plan for how to go from research to patients.’
Funded by a variety of investors, Compass has approvals to do clinical trials in 13 countries, and is presently running studies in America and Europe, including at the Institute of Psychiatry in London, and in Newcastle and Manchester.
‘The history, particularly for mental health in the pharma industry, is they’ve been selling what people don’t want to buy, but feel like they have to buy,’ Goldsmith says. ‘The conventional model of treatment works for 30 to 40 per cent of the patients – which is relatively low, but not a lot different from other areas of medicine.’
Compass has been in discussion with regulatory bodies, including NICE (The National Institute for Health and Care Excellence), about developing a care ‘pathway’ for the use of psilocybin in treating depression. ‘We need to establish data for what a safe and effective model of delivery would look like. What gets approved is not just the medicine, it’s a protocol. How will the medicine be delivered, and by whom?’
Depending on the results of further research, Goldsmith anticipates that the Compass model will be available within the next five years.
‘This isn’t going to be available in Boots and, “Good luck with that.” A person would go to their GP as they do now. The GP would do as they do now – prescribe medicine, and maybe some therapy. If that’s not effective, they would be referred to specialist care settings, which could be attached to any mental-health clinic; it would just be a different kind of room, with specially trained professionals. What we have to do from day one is to think about how to make it affordable, and how to make it accessible.’
Like Carhart-harris, Goldsmith is cautious about making extravagant claims about psilocybin – although he has personal experience of its efficacy in treating depression. His son was given ketamine treatment (which is legal in the US) and psilocybin ‘in a therapeutic environment’ to treat his chronic depression, and is now, Goldsmith says, ‘doing really well’.
‘This isn’t a place to be fast and loose,’ he continues. ‘It’s a place to do the highest quality science at the biggest and best scale you can. But we need to get it absolutely right.’
Psychedelic research was out in the cold for 50 years. ‘If we get it wrong,’ Goldsmith says, ‘are we going to wait for another 50?’