A hallucinogenic compound found in “magic mushrooms” could lead to a new antidepressant, says research published in The Lancet Psychiatry.

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Psilocybin is the psychedelic ingredient in magic mushrooms.

Psilocybin occurs naturally in some kinds of mushroom. Best known for its psychedelic effects, recent studies suggest it could help people with alcohol dependence, end-of-life anxiety, and obsessive-compulsive disorder (OCD).

Recent research has also questioned the idea that psychedelic substances have a negative effect on mental health. Some evidence suggests that psychological distress and suicidality may be lower among previous users of psychedelics, compared with users of other substances.

Like existing antidepressants, psilocybin targets the serotonin receptors in the brain. Human and animal brain images indicate that its effects may be similar to those of other treatments.

This could make it useful for treating depression, which affects 6.7 percent of Americans aged 12 years and over.

Cognitive behavioral therapy (CBT) and antidepressants are common treatments, but 1 in 5 patients do not respond to therapy, and many relapse.

Researchers led by Dr. Robin Carhart-Harris, of Imperial College London in the United Kingdom, enrolled 12 participants in the current investigation into how psilocybin might help people with depression.

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The six women and six men had moderate to severe depression for an average of 17.8 years that was not responding to treatment. They had all taken two courses of antidepressants without success, each lasting for 6 weeks or more. Eleven subjects had attended psychotherapy sessions.

None had any personal or family history of psychotic disorder, or any history of suicide or mania, and none were currently drug- or alcohol- dependent.

Participants attended 2 days of treatment. On the first, a 10-milligram dose of psilocybin was given as a test. A week later, subjects took a higher, therapeutic, dose of 25 milligrams.

The patients took the capsules while lying on a treatment bed, in a special room with low lighting and music, accompanied by two psychiatrists, one on each side of the bed. The therapists provided support and checked how patients were feeling throughout the process.

Patients were followed up 1 day after the first dose. On the day after the second dose, they had a magnetic resonance imaging (MRI) scan. Follow-up continued at 1, 2, 3, and 5 weeks, and 3 months after the second dose.

Results suggest that psilocybin, used with supportive therapy, is safe and well-tolerated. By the 3-month follow-up, about half the participants had seen a reduction in the symptoms of depression.

Detectable psychedelic effects were experienced 30-60 minutes after taking the capsules. The effect peaked at 2-3 hours. Patients were discharged 6 hours later.

There were no serious adverse effects. As expected, patients felt temporarily anxious before or as the psilocybin effects started. Nine felt some confusion, four had temporary nausea, and four had a passing headache. Two experienced mild and passing paranoia.

One week later, symptoms of depression had improved in all the patients.

Eight of them experienced a temporary remission. After 3 months, the symptoms of seven participants continued to improve, and 5 out of 7 were still in remission. Five patients relapsed to some extent.

The authors note that while psilocybin, like most antidepressants, targets the serotonin receptors in the brain, its chemical structure is different, and it acts faster.

Treatment-resistant depression is common, disabling, and extremely difficult to treat. New treatments are urgently needed, and our study shows that psilocybin is a promising area of future research.”

Dr. Robin Carhart-Harris

A number of factors could have influenced the results.

Before the trial, the patients knew they would be taking psilocybin, and most were actively seeking treatment for depression. They may have expected some effect, since five of them had taken psilocybin in the past.

All the patients were carefully screened, and they all had agreement from their physician before starting the trial.

They also received psychological support before, during and after the trial, and the setting for the study provided a positive environment.

The authors call for more research and larger trials to confirm the findings, to understand the effects, to turn them into long-term benefits, and to see how psilocybin compares with existing treatments. In this trial, there was no comparison with a placebo.

Prof. Philip Cowen, of the University of Oxford in the U.K., notes in a linked comment that the results, after 3 months, are “promising but not completely compelling, with about half the group showing significant depressive symptoms.” Three months, he cautions, is a relatively short time in the context of a long-term illness.

Prof. Cowen points out that there is currently “intense debate about the harms of recreational drug use.”

He notes that the potentially positive effects of psychedelic treatments may be “exquisitely sensitive to individual disposition, the environmental setting, and therapeutic relationship.”

He suggests that “patients with treatment-resistant depression seeking psychological insight with a less exciting trajectory might consider the slow route offered by traditional dynamic psychotherapy.”

Read more about research into the link between psychedelic drug use and mental health problems.