Professor Rob Galloway: New England Journal of Medicine says psilocybin, magic mushrooms can treat depression

Working in A&E, I often see the terrible effects of depression, the acute impacts of self-harm and suicide attempts, and the harmful long-term effects on people’s physical and mental health.

The past few years have seen an explosion in the number of people suffering from depression, a terrible affliction; those who suffer from depression genuinely suffer.

It runs in my family, and I’ve suffered from bouts. In the 20 years of being a doctor, I’ve also had three close colleagues take their own lives after years of depression.

So you can see why I’m so desperate to see a cure. But the reality is that although more than 30 drugs are licensed to treat depression, their effectiveness is often limited, and the side effects are significant.

So it was with excitement that I read a paper, in the highly respected New England Journal of Medicine, about how large doses of psilocybin (the active ingredient in magic mushrooms) can help to cure depression that is resistant to treatment.

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A few months later, in February 2023, Australia became the first country in the world to recognise psilocybin as a medical treatment for treatment-resistant depression.

We urgently need an effective treatment: could this be the one? Indeed, this paper generated a lot of publicity, and many people were excited about this new “wonder” treatment.

But the adage, “If you are about to make an important decision, slow down if you are in a hurry”, never seemed more apt.

This microscopic study was based on a couple of hundred, primarily Caucasian, volunteers.

Participants, who had treatment-resistant major depressive episodes, were randomly assigned to receive one of three psilocybin doses (25mg, 10mg and 1mg) as a one-off tablet and had psychological support.

Three weeks later, the reduction in depression scores was significant in those taking the highest dose (25mg) compared with those on the most minor (1mg).

But before we start thinking this is great news and give all depressed patients lots of psilocybin, let’s analyse the results.

A further review showed that 12 weeks after the treatment, when you looked at the proportion of patients whose depression improved, neither the 25mg nor 10mg tablets had any statistically significant impact compared with the 1mg tablet.

So in simple terms, in the short-term, smaller doses of psilocybin did not work — and in the longer term, no quantities worked.

The raw data showed that the 10mg tablets were less effective than a 1mg dose: after 12 weeks, 5 per cent of patients on 10mg were reportedly better, but double that — 10 per cent — of those who took 1mg were better.

Furthermore, we don’t know if any improvements were due to the drug or counselling, as there was no assessment of patients who received only psychological support.

And there were significant reports of side effects, with 84 per cent of people on the highest dose experiencing headache and nausea one day after taking the tablet.

After three weeks, almost 10 per cent of the patients in the 25mg and 10mg groups had severe side effects (e.g. suicidal ideation, self-harm or hospitalisation), but only 1 per cent were in the 1mg group.

So what does this all tell us? In summary, the results are incredibly messy and are not conclusive either way.

But most importantly that we should not be so quick to jump to conclusions.

We’ve done this with antidepressants in the past, where industry-led trials were subconsciously biased towards showing drugs to be more effective than they are.

Let’s look at who sponsored the psilocybin research: mental health care company Compass Pathways.

The lead author is Compass’s chief medical officer, who has shares and stock options in this company (we know this because, at the end of the study, there is a link to the author’s declaration of interest).

This company is heavily involved in developing psilocybin as a treatment, and so set to profit greatly if the drugs become widely used.

I’m not saying they are being deliberately biased — and to be fair to them, the authors agree that the results are inconclusive and that “larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder”.

But bias is a recognised problem in scientific research.

One of the most famous bias cases was the antidepressant drug reboxetine, first approved in the UK in 1997.

An initial meta-analysis showed it was effective in treating depression in a novel way by inhibiting noradrenaline uptake outside of brain cells.

A meta-analysis combines all data from relevant available studies to conclude whether or not a treatment works — the problem is the word open. The available data in this meta-analysis was subject to publication bias — where results of studies are only published if they show that the treatment works; the studies that don’t are published.

But when, in 2010, a group of German researchers reviewed all the existing data on reboxetine — published and unpublished — they showed previous claims of how useful the drug was, were exaggerated.

The drug was “an ineffective and potentially harmful antidepressant”, they concluded in an article in the BMJ — and guidance has since been modified.

In the UK, it is now used only for major depression when other antidepressants (SSRIs) don’t work.

In the past few years, the scientific community has made massive efforts to stop publication bias by ensuring all trials are registered before they start. So all results will be published — regardless of whether they are positive or negative.

So let’s go back to psilocybin. I’m not saying there will be no evidence for the drug, but we must be cautious because, so far, it’s inconclusive.

If more substantial evidence comes to light, we should re-evaluate it. But even then, we must be careful — the side effects of psilocybin are significant, and the hallucinogenic trips can be traumatic.

In addition, a massive amount of psychological support was given to patients in this trial, which probably wouldn’t happen with the reality of what is happening to our mental health services.

Finally, we must be careful because there will be those pushing for its medical use, not because they’ve analysed the studies but because they’d like to see hallucinogenic drugs legalised and see it as a gateway into legalisation for recreational use.

So I won’t be sending patients to the woods for magic mushrooms.

I’ll look for independent assessment of the evidence as it becomes available and decide with my patients what to do.

But from this paper alone, I certainly wouldn’t be recommending it. If you or a loved one are suffering from depression, please seek help from your GP.

They may decide antidepressants could play a crucial part in your treatment — but for many (particularly with mild depression), tablets are not needed, but speaking therapies or exercise that are proven to work better, without side effects.

As for me, I was on antidepressants but found they didn’t help, and the side effects made me feel worse.

But instead of turning to mushrooms, I turned to run, which helped cure me.

So I’d suggest if you do go to the woods, run there but don’t pick the mushrooms.

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