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A hallucinogenic compound derived from magic mushrooms may offer a possible new avenue for antidepressant research, according to a new study published in The Lancet Psychiatry.
The small feasibility trial, which involved just 12 people with treatment-resistant depression, found that psilocybin was safe and well tolerated and that, when given alongside supportive therapy, helped reduce symptoms of depression in about half of the participants at three months post-treatment.
The authors warned, however, that strong conclusions could not be made about the therapeutic benefits of psilocybin, and that more research in this field was now needed.
“This is the first time that psilocybin has been investigated as a potential treatment for major depression,” said lead author Dr Robin Carhart-Harris of Imperial College London. “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. The results are encouraging and we now need larger trials to understand whether the effects we saw in this study translate into long-term benefits, and to study how psilocybin compares to other current treatments.”
Depression is a major public health burden, affecting millions of people worldwide and costing the US alone more than US$200 billion (€177.4bn) per year. The most common treatments for depression are cognitive behaviour therapy (CBT) and antidepressants. However, one-in-five patients with depression do not respond to any intervention, and many relapse.
“Previous animal and human brain imaging studies have suggested that psilocybin may have effects similar to other antidepressant treatments,” added Prof David Nutt, senior author from Imperial College London. “Psilocybin targets the serotonin receptors in the brain, just as most antidepressants do, but it has a very different chemical structure to currently available antidepressants and acts faster than traditional antidepressants.”
The trial involved 12 patients (six women, six men) with moderate-to-severe depression (average length of illness was 17.8 years). The patients were classified as having treatment-resistant depression, having previously had two unsuccessful courses of antidepressants (lasting at least six weeks). Most (11) had also received some form of psychotherapy. Patients were not included if they had a current or previous psychotic disorder, an immediate family member with a psychotic disorder, history of suicide or mania or current drug or alcohol dependence.
Patients attended two treatment days — a low (test) dose of psilocybin 10mg oral capsules, and a higher (therapeutic) dose of 25mg a week later. Patients took the capsules while lying down on a ward bed, in a special room with low lighting and music, and two psychiatrists sat either side of the bed. The psychiatrists were present to provide support and check in on patients throughout the process by asking how they were feeling.
Patients also had an MRI scan the day after the therapeutic dose. They were followed up one day after the first dose, and then at one, two, three, and five weeks and three months after the second dose.
The psychedelic effects of psilocybin were detectable 30-to-60 minutes after taking the capsules, and peaked at between two and three hours.
Patients — who were discharged six hours later — had no reported serious side-effects. Expected side-effects included transient anxiety before or as the psilocybin effects began (all patients), some experienced confusion (9), transient nausea (4) and transient headache (4). Two patients reported mild and transient paranoia.
At one week post-treatment, all patients showed some improvement in their symptoms of depression. Eight of the 12 (67%) achieved temporary remission. By three months, seven patients (58%) continued to show an improvement in symptoms and five of these were still in remission. Five patients showed some degree of relapse.
The patients knew they were receiving psilocybin and the effect of psilocybin was not compared with a placebo. The authors also stress that most of the study participants were self-referred, meaning they actively sought treatment, and may have expected some effect (five had previously tried psilocybin before). All patients had agreement from their GP to take part in the trial.
Further research was now needed to tease out the relative influence of these factors on symptoms of depression, the authors noted, and to examine how psilocybin compared to placebo and other current treatments.
Lancet Psychiatry 2016, Published Online May 17, 2016, http://dx.doi.org/10.1016/S2215-0366(16)30065-7.