Psychedelics will not solve the mental health crisis

Let's not pretend that people with severe mental illness stand to benefit from the development of psychedelic therapy

Are psychedelic drugs the answer to the mental health crisis? asked a headline in The Times a couple of years ago. Similar questions have been posed by Radio 4 and BBC News. The Times article is based on an interview from Professor Robin Carhart-Harris, previously at the Centre for Psychedelic Research, Imperial College London, now based in California. I’m going to quote him at length as it is a reflection of the the field’s general vibe.

He starts off with the usual spiel about conventional antidepressants being only a superficial help:

‘But the cost of that is people say they’re not really living. They have to live two years to experience one — life is muted somehow, emotion is muted.’

By contrast, psychedelics are described thus:

‘It begins with an opening and a loosening of the mind, Carhart-Harris says. ‘The action is one of insight — revelation, self-understanding, perspective change.’

You get a sense of how he views psychiatric disorders more generally:

‘Mental illness is acquired — you are certainly not born with it,’ he continues. While some people may have an innate ‘vulnerability’ or ‘sensitivity’, it is the ‘vicissitudes of life’ that trigger the descent into mental illness, he says.

The hype isn’t just coming from the media. This month an editorial, Is it now time to prepare psychiatry for a psychedelic future? was published in the British Journal of Psychiatry. The lead author is another proponent of psychedelic-therapy, Professor David Nutt (who notably is also the Chief Research Officer for Awakn Life Sciences, a biotech company developing ketamine and MDMA treatments for addiction).

The editorial argues that psychiatry training needs to incorporate psychedelic therapies as soon as possible:

‘The fact that psychedelic therapy involves psychological as well as pharmacological intervention for severe mental illness means that psychiatrists are the best trained and equipped group to deliver this new therapy.’

I won’t be the first to notice the hype surrounding these drugs is unlike any other in psychiatry. However, in this post I will argue that, in contrast to Professor Nutt’s assertion, psychedelics will never be an answer for severe mental illness.

The hype

Let’s speak about the hype - we all know it’s there and it’s not limited just to media or even researchers with a vested interest; the buzz around psychedelic research seems to have infected supposedly objective academic outlets.

There are many instances of high impact journals publishing research which, if not flawed, is certainly substandard. A recent example is a meta-analysis of psilocybin for treatment resistant depression published in The BMJ, one of the most prestigious medical journals. Unusually for a meta-analysis, this had only two authors, one of whom was a graduate student (not a criticism in itself, I’m one too). Within two days of being published, it was noted that the calculated effect sizes were implausibly big, likely stemming from mistaken use of the standard error of the mean rather than standard deviation. To its credit, The BMJ immediately posted an expression of concern and the authors quickly admitted the mistake. Honest mistakes happen all the time - that’s part of science, error correction is how we progress. But it does make you wonder if we are overlooking rigour in favour of glamour.

Another example comes from JAMA Psychiatry, one of the highest ranking journals in mental health. Last year they published a nonrandomised controlled trial of 15 people with bipolar disorder. (As will later become relevant, all the participants had bipolar type II and anyone with a history of mania, or psychosis, or delusions, or paranoia, or substance use was excluded). Despite the name, there was no control group - it was, essentially, a case series. Remember that as empiricists we like our trials placebo-controlled, double-blind, and randomised. Without a control group, we cannot know if improvements in the participants were down the the drug or some other factor. Now don’t get me wrong, I’ve nothing against case series but you have to question what it would take for an n=15 case series to be published in a leading psychiatric journal, if it didn’t have psilocybin in the title. Embarrassingly, JAMA Psychiatry had to issue a correction revising the title from controlled trial, to open label trial.

You can probably see how these unforced errors from journals and hasty corrections damage everyone’s credibility. I’ll give one more example. This time from Nature Medicine - not quite ‘Nature Nature’ but still within the top five medical journals. In 2022, it published a functional MRI study of psilocybin in treatment resistant depression. The authors (including the aforementioned Professor Nutt) concluded that the psychedelic had a ‘liberating’ effect on the brain and that this was a ‘robust, reliable and potentially specific biomarker of response’.

Twitter was quick to question the statistical analysis and a full critique was later posted on PsyArXiv by Manoj Doss, Fred Barrett and Phil Corlett. They go through, point-by-point, a list of what is generously termed questionable research practices. One line really got me - ‘it was disappointing to see a less-than-rigorous one-tailed test in Nature Medicine’. This sounds polite but is an example of scientists throwing the utmost shade.

The back and forth between the authors and critics was covered superbly in Vice (RIP), by Shyla Love. Incredibly, she interviewed one of the peer-reviewers who admitted not picking up some of the statistical shenanigans. Again, questionable research practices are not confined to the psychedelic field, but this adds to the feeling that high-impact journal can give a free-pass to research they wouldn’t accept in other circumstances.

The backlash

With great hype comes great backlash; it’s a fundamental law of science. People (like me), enjoy going through high impact research and finding obvious errors when we suspect the yield will be high. In fact, I have resisted writing about psychedelics, up to this point, because so many others with bigger audiences got there and trashed it first.

A comprehensive guide to red flags in psychedelic research has been posted by Eiko Fried. He starts by saying, rightly, that we don’t yet know whether these drugs are a safe and effective treatment for depressive disorders. He then goes on to list problems with research to date.

These include:

• Lack of blinding - if you are given a psychedelic, you usually know about it

• Lack of control groups - think back to that nonrandomised, open label trial

• Conflicts of interest - many researchers will have a financial interest in psychedelic therapy being successful

• External validity - the study participants are highly selected and in some cases are psychedelic enthusiasts

• Follow-up times - these are as short as one week in some trials

Stuart Ritchie covers many of these issues while highlighting that many researchers are aficionados of psychedelics themselves. This could well affect how the research is conducted, reported, peer-reviewed, and communicated to the media.

While the field of psychedelic research has come in for criticism, potential dangers of psychedelic therapy have come to light too. Almost by design, patients under the influence of these drugs are in an incredibly vulnerable position and require the most stringent safeguards. Unfortunately, it seems this has not always been the case. Allegations of sexual assault have emerged in trials of MDMA–assisted therapy for PTSD.

More generally, the harms of psychedelic-therapy are poorly recorded and reported in clinical trials. Potential harms which have been reported and warrant further investigation include emergent suicidality, development of mania or psychosis, abuse from therapists, and dependency (if not on the drug then on the therapy itself). I don’t want to over-do this, I’m sure many people will undergo this treatment in a controlled and safe manner. However, if we are thinking of upscaling this form of therapy to the NHS we have to systematically assess both the benefits and risks.

Psychedelics may be helpful for some

Right. I will now set aside the hype and the backlash, to steel-man the case for psychedelic therapy. Because I do want this to work. Yes I enjoy pointing out mistakes in psychedelic research published in prestigious journals, but deep down I want these drugs to be successful, as they could help people suffering from mental distress.

Firstly, we have to acknowledge that psychedelics come in a period of pharmacological stagnation in psychiatry. Sadly, most drugs for mental illness are mere derivatives of those discovered serendipitously in the 1950s. While the side-effect profile of medications today may be slightly superior, their efficacy isn’t. We are crying out for new treatments that improve the lives of those suffering from mental disorders.

Psychedelics, while not new, certainly have a novel mechanism of action compared to conventional medications. Incorporating psychedelic therapy into psychiatric treatment would, genuinely, be a paradigm shift. If you can see past the colourful claims about these drugs liberating the depressed brain, there is a plausible psychological mechanism in giving these drugs to people who have become trapped in rigid patterns of behaviour and thinking.

Many of the experiences reported by people under psychedelics do sound meaningful and anecdotally have helped them process traumas. I completely believe people who say they have found benefit, even transformational benefit from psychedelics.

I am not convinced the criminalisation of these drugs (perhaps any drug) is beneficial to individuals or society more generally. The legal difficulties in conducting research using these compounds has surely impeded our understanding of mental disorders and the brain.

Can I imagine high quality, large randomised controlled trials showing these drugs to be effective? Yes. Could they convince me the drug was having a therapeutic effect over and above researcher bias, unblinding, expectancy, or questionable research practices? Yes, I am ready to be convinced.

Could I imagine psychedelics being used in the NHS? Yes, I can imagine this, in a limited, restricted capacity. Within mental health services we do use treatments, with less empirical evidence which are high cost (I’m thinking of psychodynamic psychotherapy) though usually only for selected patients in specialist settings. I can more easily imagine psychedelic therapy thriving in the private sector, similarly to ketamine clinics today.

Who could I imagine benefiting, if it does gain approval? Most of the trials seem to focus on treatment resistant depression or PTSD. I can imagine it helping people process trauma. I can imagine it helping people who have become stuck in unhelpful patterns of thinking. I find it difficult to believe it will help people who have more ‘biological’ forms of depression, the type with early morning wakening, diurnal variation in mood, weight loss, psychomotor retardation. For an insight into this, read this personal description by the psychiatrist Iain McGilchrist:

I first experienced this at the age of 20 without any identifiable cause. On paper my life was going fine, yet for weeks I could not eat without feeling sick. Then I pretty much stopped eating. I could not concentrate enough to read or even watch TV. Sight seemed dim, but oddly sound was tormentingly magnified. I knew nothing of depression—nobody had it, apparently, when I was young. I eventually twigged that I must be ill when, waking to writhe and sweat as usual at 3 or 4 am, I heard a bird singing outside my window. My immediate thought was ‘that bird is singing only because it is in so much pain: it has a tumour and knows it is going to die’. Some little bit of sanity left in me thought that was a rather odd thing to be thinking, and I asked to see a psychiatrist, who sensibly skipped my potty-training and prescribed amitriptyline, an anti-depressant. Five and a half weeks later—I can remember the morning very distinctly; it was one Tuesday in Oxford in 1973—I woke feeling like Rip van Winkle. I looked around, noticed that the colours were literally brighter, and thought ‘I remember this world!’ Over the next few weeks it was a world I came to join again. In retrospect, I realised that I had been ill for eighteen months.

Will psychedelics be helpful for such cases of depression that seem to arise and recur out of the blue? I’m not so sure. Notably, these severe forms of the illness seem to respond particularly well to conventional antidepressants. Crucially I also struggle to imagine psychedelics helping the bulk of patients cared for by secondary mental health services - people living with severe mental illness.

Psychedelics are not a cure for mental illness

Most psychiatrists (in the NHS anyway) spend their time treating people with mental illnesses like schizophrenia, bipolar disorder, severe depression, and personality disorders. Many of the patients we see have additional substance misuse. They will often have some element of risk, either to themselves (through suicidal behaviour or self-neglect) or less frequently, to others.

These patients are those most in need of treatment, but it is difficult to see what psychedelic therapy can offer them. In fact, such patients are actively excluded from clinical trials. The largest trial of psilocybin for depression excluded participants with a history of psychotic illness, personality disorder, or ‘or any serious psychiatric comorbidity’. They excluded those with substance or alcohol misuse in the past year. They excluded participants who had suicidal thoughts or behaviours in the past year.

Another recent phase 2 trial of psilocybin excluded participants for as little as a family history of psychosis. They additionally excluded those with ‘a psychiatric condition judged to be incompatible with establishment of rapport with the facilitators or safe exposure to psilocybin’. The samples from these studies are not only unrepresentative of people with mental illness, they aren’t even reflective of the general population. Roughly half of the participants had an annual income of more than $100,000. These are a different group of people than we typically see as psychiatrists, with a different set of problems.

I know many of the readers of this newsletter have worked in mental health services in some capacity, perhaps in community mental health teams or psychiatric inpatient units. I wonder how many of your patients would fit the profile of the participants in trials of psychedelics. How many would benefit from undergoing a psychedelic experience? How many would be safe to take psychedelics - free of a family history of psychosis, free of alcohol or substance misuse, free of suicidal thoughts. For many clinicians I suspect the answer is none.

The other mental health crisis

When people speak about the ‘mental health crisis’ (alternatively described as a tsunami or epidemic) they usually mean increased rates of loneliness, or stress, or antidepressant prescriptions. I have no doubt this is the mental health crisis psychedelic proponents are targeting.

However, there is another crisis we see everyday in psychiatric services, it is one affecting people with severe mental illness. On the ground, the crisis is a lack of funding and inpatient beds. In the past ten years, available mental health beds in England have shrunk from 23k to under 18k while detentions under the Mental Health Act have increased.

It has become normalised that patients requiring inpatient mental health care, usually in the midst of an acute psychotic or suicidal episode, will wait days for a bed in a psychiatric unit. In that time they will languish in A&E departments (often sitting on chairs, not even in a bed). When a bed is found, it may be in another part of the country, miles away from the person’s home. Less commonly, lack of inpatient beds to detain someone under the Mental Health Act has been linked to homicides committed by people with psychotic illnesses.

This would be completely unacceptable for other medical needs - how has it become tolerated for those with the severest forms of mental illness?

Psychedelics may help with some problems. But if you are someone who suffers from severe mental illness, or suicidal ideation, or even a family history of psychosis, these drugs are not being developed for you. They might be part of a solution for a crisis in mental health, but this cannot distract us from addressing the real crisis affecting people living with mental illness.