Magic mushroom ingredient tested as depression treat...

"Magic mushrooms 'promising' in depression," BBC News reports. Magic mushrooms is an umbrella term for fungi that contain psilocybin, a psychoactive substance that can cause intense LSD-like hallucinations, as well as reported feelings of euphoria and "spiritual insight".

Researchers gave two doses of psilocybin to 12 volunteers, all of whom had moderate or severe depression that had not responded to other treatment. As this drug is controlled in the UK, permission from the Home Office was needed for the study, and the participants were closely monitored by psychiatrists.

The intention was to monitor the "intensity" of the experience, as reported by the volunteers, to see if it was feasible to use psilocybin to treat people with severe depression. The researchers also wanted to get an initial impression of its effects.

They found the 12 volunteers tolerated the drug, with minor side effects that did not last long. Eight of them had no symptoms of depression one week after treatment, and five were free from depression after three months.

But because of the type of study this is and its small size, we can't be sure if these results are the result of psilocybin.

The researchers warn that people should not try to treat themselves with mushrooms that contain psilocybin. Aside from their unpredictable effects, magic mushrooms are class A drugs that are illegal to possess – which can carry a seven-year jail sentence – or distribute, which can result in up to life imprisonment.

Where did the story come from?

The study was carried out by researchers from Imperial College London, South London and Maudsley NHS Trust, King's College London, University College London, the Royal London Hospital, and the Beckley Foundation.

It was funded by the Medical Research Council.

The study was published in the peer-reviewed journal The Lancet: Psychiatry on an open-access basis, so it's free to read online.

While overall the UK media reporting was accurate, The Sun newspaper wins the most inappropriate headline of the month award (and is currently a leading contender for 2016).

Their headline, "Magic mushrooms make you a fun guy", manages to both trivialise the life-limiting and often horrible impact severe depression can have, while simplifying the complex results of this study.

The Sun also used a stock photo of a classic twentysomething cheesy raver with the caption: "Professor Nutt, who worked on the study, was previously sacked as the Government's chief drug adviser in 2009". The distinguished 65-year-old psychiatrist may be a little put out (or possibly amused) by this.

The Daily Mail was also overenthusiastic in its reporting, saying that "Hundreds of thousands of people could benefit from antidepressants derived from magic mushrooms", despite the limited nature of the study.

However, both The Guardian and The Independent give a more measured account of the study and its limitations.

What kind of research was this?

This was an open-label feasibility study designed to test whether the drug psilocybin could be safely given to selected patients with depression, alongside psychological support.

Everyone in the study took the drug, meaning there was no comparison group and everyone knew that they were taking the drug.

That said, it is hard to imagine what could serve as a placebo for a drug (psilocybin) notorious for its hallucinogenic properties.

This type of early-stage trial cannot give us reliable information on efficacy – nor is it set up to do so.

Even if such a trial suggests possible effectiveness, it's hard to be sure whether the results are truly down to the drug or whether they could reflect an "expectation" effect, where people immediately felt better because that is what they expected.

What did the research involve?

Researchers publicised their study, saying they wanted to recruit people with depression that had not responded to other treatments to test psilocybin. Only 12 of the 72 volunteers met the study requirements.

After physical and mental health tests – including checks to make sure the volunteers were not at high risk of psychosis – they were given two doses of psilocybin in hospital, one week apart.

The first was a low dose to check for unexpected reactions, while the second was a high dose aimed at treating depression. The day after treatment, people were asked about their experiences, including the intensity of psychedelic effects (on a scale of 0 to 1) and any unpleasant effects.

Everyone was followed up regularly, by telephone or email, from the day after the high-dose treatment until three months afterwards. Participants filled in questionnaires designed to monitor depression symptoms.

Researchers compared depression scores from before the study began, one week after treatment, and three months after treatment.

What were the basic results?

On average, people rated the intensity of the experience as 0.5 for the low-dose and 0.75 for the high-dose treatment. Psychedelic effects typically appeared from 30 to 60 minutes after taking the dose, peaked after two to three hours, and were no longer detectable after six hours.

Nobody had to be sedated during the treatment. The main side effects were feeling anxious (which happened to everyone), confusion, nausea and headache. None of these side effects lasted. Average depression scores decreased at one week and remained lower at three months.

Because the study is so small, it may be more useful to look at what happened to the individuals, rather than average depression scores.

After one week, eight people responded to the medicine with reduced depression scores of at least half their previous score, suggesting a big improvement. Seven of them fell into the range that suggested they no longer had depression.

However, most people's depression scores increased over the next three months, and only five of the original 12 volunteers were still free from depression at the end of the study.

At the end of the study, six people had mild or moderate depression, and one person once again had severe depression.

How did the researchers interpret the results?

The researchers said that: "Done with appropriate safeguards, [such as careful screening and therapeutic support] psilocybin can be safely administered" to patients with depression.

They admitted that the study design means "strong inferences cannot be made about the treatment’s therapeutic efficacy" – in other words, we can't be sure that it worked. They went on to say that: "The data do suggest that further research is warranted".

They pointed out that it is rare for people with severe depression to recover spontaneously without treatment, and most of their participants had lived with depression for many years.

They have called for a bigger randomised controlled trial to properly assess how well this treatment works.

Conclusion

Depression is a disabling disease that affects many people in the UK. While antidepressants and therapy work for many people, some people don't fully respond to treatment.

A treatment for depression that uses a drug that works in a different way from existing antidepressants could be very helpful.

Having said that, this study doesn't tell us whether psilocybin is a useful drug for treating depression. This was a very small, early-stage trial that only aimed to see whether the drug was safe and has potential for use – the researchers did not set out to see if the drug is effective for treating severe depression.

Here are some points to consider:

Ten of the recruits had referred themselves, rather than being referred by a doctor. This means they actively sought out treatment with psilocybin. Interestingly, five of the 12 had taken psilocybin before, which may mean they joined the study because they already thought the treatment worked for them.
There was no control group and no placebo – everyone was given the treatment and knew they were taking the treatment. This means we don't know whether the treatment itself or another factor, such as the intensive therapeutic support from psychiatrists, might have caused the improved depression scores.
The chart showing the depression scores for each individual shows that most people (not everyone) had a big initial drop in depression scores by one week after treatment, followed in many cases by a fairly sharp upswing in scores after that. This could mean that the experience of having the treatment has a short-term effect that wears off fairly quickly for most people.

Researchers and funders will review the results of the study and decide whether to build on this with a large randomised controlled trial.

This would give us a better indication of whether this treatment could work for people with depression who are not helped by current treatments – and, most importantly, whether it's safe for use.

We imagine that because of the ongoing political controversies around psychoactive drugs like psilocybin, ketamine and MDMA being used to treat mental health conditions, a larger follow-up phase II trial is not guaranteed to take place.