Researchers at Imperial College London have given twelve people psilocybin, the active component in magic mushrooms, to combat depression (Nature, 2016, BBC, 2016).

At the start of the trial, nine of the participants had at least severe depression and three were moderately depressed. All had been clinically depressed for a significant amount of time, on average 17.8 years. One patient had been depressed for thirty years. None of them had responded to standard medications, such as selective serotonin re-uptake inhibitors (SSRIs), or had electroconvulsive therapy. They had all had tried at least two different treatments for depression, without success. One had tried eleven different treatments.

The study initially gave patients a low dose of psilocybin to test its safety. They were then given a very high dose, which was, according to the researchers, equivalent to “a lot of mushrooms.” The psychedelic experience lasted up to six hours, peaking after the first two, and was accompanied by classical music. Afterwards the participants received psychological support.

“These experiences with psilocybin can be incredibly profound, sometimes people have what they describe as mystical or spiritual-type experiences.”said Dr Robin Carhart-Harris, a neuropsychopharmacologist at Imperial College London and first author of the latest study, which is published in The Lancet Psychiatry.

Most patients had a rapid dip in their depressive symptoms, with predictable side effects including anxiety, nausea and headaches. Robin Carhart-Harris said “Seeing effect sizes of this magnitude is very promising, they are very large effect sizes in any available treatment for depression. We now need larger trials to understand whether the effects we saw in this study translate into long-term benefits.”

One week after receiving an oral dose of psilocybin, all participants experienced a marked improvement in their symptoms. Three months on, five patients were in complete remission. Robin Carhartt-Harris said “That is pretty remarkable in the context of currently available treatments.” The equivalent remission rate for SSRIs is around 20%.

Senior study author Professor David Nutt, a neuropsychopharmacologist at Imperial College, said thoughts could become locked in an overly self-critical and negative mode in depression, and it was thought psilocybin acted as a “lubricant for the mind” that “liberates” the patient. He said psilocybin targeted the receptors in the brain that normally responded to the hormone serotonin, which was involved in mood.

The study’s authors are not suggesting that psilocybin should be a treatment of last resort for depressed patients. Robin Carhart-Harris said “Our conclusion is more sober than that — we are simply saying that this is doable. We can give psilocybin to depressed patients, they can tolerate it, and it is safe. This gives us an initial impression of the effectiveness of the treatment.”

Magic mushrooms are categorised as a Class A drug in the UK, the same category as heroin and cocaine. The ethics committee that granted approval for the trial was so concerned that the participants could experience delayed onset psychotic symptoms it requested the three month follow-up on the subjects. This was “unprecedented”, according to David Nutt. He said it took thirty two months between having the grant awarded and dosing the first participant. By comparison, it took six months for his team’s previous studies using LSD and MDMA. David Nutt said of the magic mushrooms trial:

Every interaction — applying for licenses, waiting for licenses, receiving the licenses, applying for contracts for drug manufacture, on and on — involved a delay of up to two months. It was enormously frustrating, and most of it was unnecessary. The study result isn’t the remarkable part — it’s the fact that we did it at all.

He said simply being able to perform the study was a “landmark”, as he criticised the “Kafkaesque” restrictions on the research difficult. David Nutt, who was fired as the government’s drugs adviser for his outspoken views, said red tape had meant “it cost £1,500 to dose each patient, when in any sane world it might have cost £30.”

Experts cautiously welcomed the findings. Professor Philip Cowen, from the University of Oxford, said:

The key observation that might eventually justify the use of a drug like psilocybin in treatment-resistant depression is demonstration of sustained benefit in patients who previously have experienced years of symptoms despite conventional treatments, which makes longer-term outcomes particularly important. The data at three-month follow-up, a comparatively short time in patients with extensive illness duration, are promising, but not completely compelling.

The study only involved a small number of people and had no placebo group. The researchers said “it is possible” all the improvement was down to the placebo effect although the duration of the benefit and change in outlook suggested something else was going on. Robin Carhart-Harris said “this isn’t a magic cure, we shouldn’t infer too much” until larger trials had taken place.

Scientists at the Heffter Research Institute in Santa Fe, New Mexico, have been investigating how psilocybin could be used to alleviate depression and anxiety in people with terminal cancer, but this is the first study to look specifically at how psilocybin could be used to treat depression alone.

The World Health Organisation calls depression “the leading cause of disability worldwide”. But effective therapies are hard to find. Searching for new treatments, researchers have looked to potent and quirky alternatives such as ketamine and ayahuasca, both of which have shown promise in clinical trials.

Glyn Lewis, who studies psychiatric disorders at University College London, said “It’s worth noting that we have not developed any new treatments which are widely used since the 1970s for depression, despite the fact that this is the major public-health problem in the Western world and middle-income countries.” He said it was particularly interesting that psilocybin seems to take effect with a single dose, unlike some current medications for depression that must be taken daily. He said “This study is simply asking: is this interesting enough to pursue further as a treatment for depression? My own judgement is that yes, it is.”

The research was backed by the Beckley Foundation and the MRC.

This article originally appeared on this website with the title ‘Magic mushroom drug lifts depression in first human trial’