Can magic mushrooms really cure depression? Professor Bob Galloway finds the answers

When I work in the emergency room, I often see the terrible effects of depression; the acute consequences of self-harm and suicide attempts, but also the harmful long-term effects on people’s physical and mental health.

In recent years there has been an explosion in the number of people suffering from depression, and it is a terrible condition; for those who suffer from depression really suffer.

It runs in my family and it bothered me. In my 20 years as a doctor, I have also had three close colleagues commit suicide after years of depression.

So you can see why I’m so desperate for a cure. But the reality is that even though there are more than 30 medications approved to treat depression, their effectiveness is often limited and the side effects significant.

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

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

We desperately need an effective treatment: could this be the only one?

Sure, this paper generated a lot of publicity and many people got very excited about this new “miracle” treatment. But the old adage, “When you’re about to make an important decision, slow down if you’re in a hurry,” never seemed more appropriate.

This was a very small study based on a few hundred mostly white volunteers. Participants, who had treatment-resistant major depressive episodes, were randomly assigned to one of three doses of psilocybin (25 mg, 10 mg, and 1 mg) as a single tablet and received psychological support.

Three weeks later, the reduction in depression scores was significant in those taking the highest dose (25 mg) compared to those taking the smallest (1 mg).

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

Another study found that 12 weeks after treatment, when you looked at the number of patients whose depression improved, neither the 25 mg tablets nor the 10 mg tablets had any statistically significant effect compared to the 1 tablet. mg.

So in simple terms, in the short term smaller doses of psilocybin didn’t work – and in the longer term no doses worked.

In fact, the raw data showed that the 10 mg tablets were less effective than a 1 mg dose: After 12 weeks, 5 percent of patients on 10 mg were said to be better, but double that – 10 percent – of those taking 1 mg names was better. In addition, we do not know whether any of the improvements were due to the drug or to counseling, as there was no assessment of patients who received psychological support alone.

And there were significant reports of side effects, with 84 percent of people taking the highest dose experiencing headaches and nausea a day after taking the tablet.

After three weeks, nearly 10 percent of patients in the 25 mg and 10 mg groups had serious side effects (for example, suicidal thoughts, self-harm, or hospitalization), but only 1 percent in the 1 mg group.

So what does all this tell us? In summary, that the results are incredibly messy and unconvincing anyway.

But above all that we should not jump to conclusions so quickly. We’ve done this in the past with antidepressants, where industry-led studies unknowingly focused on showing drugs that were more effective than they are.

Let’s see who sponsored the psilocybin study: mental health company Compass Pathways. The lead author is the medical director of Compass who has stock and stock options in this company (we know this because there is a link to the author’s declaration of interests at the end of the study).

This company is heavily involved in the development of psilocybin as a treatment and will therefore greatly benefit from the drugs being used on a large scale. I’m not saying they’re intentionally biased – and to be fair, the authors agree that the results are inconclusive and that “larger and longer studies, including comparison with existing treatments, are needed to confirm the efficacy and safety of psilocybin.” for this disease’.

But bias is a recognized problem in scientific research. One of the most famous cases of bias was that of the antidepressant reboxetine, which was first approved for use in the UK in 1997.

A first meta-analysis showed that it was effective in treating depression in a new way, by inhibiting norepinephrine uptake outside brain cells. A meta-analysis combines all the data from relevant available studies to arrive at a conclusion about whether or not a treatment works – the problem is the available word.

The available data in this meta-analysis was subject to publication bias – results of studies are only published if they show that the treatment works; the studies that don’t simply don’t get published.

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

In fact, the drug was “all in all an ineffective and potentially harmful antidepressant,” they concluded in an article in the BMJ — and the guidelines have since been updated. In the UK it is now only used for major depression when other antidepressants (SSRIs) have not worked.

In recent years, the scientific community has made enormous efforts to stop publication bias by ensuring that all studies are registered before they start, so that all results are published – whether positive or negative.

So let’s go back to psilocybin.

I’m not saying there won’t be evidence for the drug, but we have to be careful because so far it’s inconclusive.

If stronger evidence comes to light, we should reevaluate it. But even then we have to be careful – the side effects of psilocybin are significant and the hallucinogenic trips can be traumatic.

In addition, a tremendous amount of psychological support was given to patients in this trial — something that probably wouldn’t happen with the reality of what’s happening with our mental health system.

Finally, we have to be careful because there will be those who push for medical use, not because they have analyzed the studies, but because they want to see hallucinogenic drugs legalized and see it as a gateway to legalization for recreational use.

So I’m not going to send patients to the forest for magic mushrooms. I will seek an independent review of the evidence as it becomes available and decide with my patients what to do. But based on this article alone, I would definitely not recommend it.

If you or a loved one suffer from depression, seek help from your GP.

They may decide that antidepressants can play a vital role in your treatment, but for many (particularly with mild depression) it’s not tablets that are needed, but talk therapies or exercise that have been proven to work better, with no side effects.

As for me, I took antidepressants but found they didn’t help and the side effects made me feel worse. But instead of turning to mushrooms, I took up running — and that helped me heal.

So I suggest that if you go to the forest, run there, but don’t pick mushrooms.