Globally, it is estimated that almost 300 million people suffer from depression, equivalent to 4.4% of the world's population, according to data from the Pan American Health Organization. This mental health condition has increased during the COVID-19 pandemic. However, even the best performing antidepressant drugs show modest efficacy, not negligible side effects, discontinuation problems and high relapse rates, highlighting the need for new and improved treatments.
Patients diagnosed with depression often have a negative cognitive bias, characterized by pessimism, poor cognitive flexibility, rigid thought patterns, and negative fixations regarding themselves and the future.
Over the past 15 years, at least six separate clinical trials have reported dramatic improvements in depressive symptoms with therapy with psilocybin, a fungus with hallucinogenic properties.
The findings of a new analysis of brain scans of nearly 60 people receiving treatment for depression, led by the Psychedelic Research Centre at Imperial College London show that it may have been unraveled how psilocybin exerts effects therapeutic effects on the brain. This is one of several psychedelics that are being explored as a potential therapy for psychiatric disorders.
Experts warned that it is a therapy that should be avoided without strict medical control, as it can generate an unwanted effect.
Several studies have tested a synthesized form of the drug to treat patients with depression and anxiety, with promising results. The new signs, taken from two combined studies, reveal that people who responded to psilocybin-assisted therapy showed greater brain connectivity not only during treatment, but up to three weeks later. This openness effect was associated with self-reported improvements in her depression. However, similar changes in brain connectivity were not observed in those treated with a conventional antidepressant (called escitalopram), suggesting that psychedelic works differently in the treatment of depression.
According to the team, the findings, published in the journal Nature Medicine, are a promising development. They explain that patterns of brain activity in depression can become rigid and restricted, and that psilocybin could potentially help the brain break out of this routine in a way that traditional therapies cannot.
The lead author of the article, Robin Carhart-Harris, former head of the Imperial College for Psychedelic Research which is now based at the University of California, San Francisco, indicated that “the effect seen with psilocybin is consistent in two studies and the same effects were not seen with a conventional antidepressant. In previous studies, we had seen a similar effect on the brain when people were scanned while taking a psychedelic, but here we observed it weeks after treatment for depression, suggesting a remnant of the drug's acute action.”
Initial findings from two studies conducted at Imperial College reported a reduction in depression measures, but the mechanism that underpins how treatment exerts these effects is unclear. In the latest study, a team led by Imperial's Psychedelic Research Center analyzed the functional magnetic resonance imaging of the participants in these two trials, which included nearly 60 people: an open trial in treatment-resistant depression, where all participants received psilocybin; and a randomized control trial in more general depression that compared psilocybin with escitalopram, a selective serotonin reuptake inhibitor (SSRI).
All participants also received therapies with registered mental health professionals and had brain scans taken before, and then one day and three weeks after the participants received psilocybin therapy. Both trials detected improvements with psilocybin therapy, as measured by participants' scores in the clinical questionnaires. Analysis of brain scans revealed altered communication or connectivity between brain regions. More specifically, they found an increase in communication between those regions of the brain that are most segregated in depressed patients. They detected a correlation between this effect and the improvement in symptoms in both trials; although the strength and duration of the effect varied among participants, it was stronger in those who reported an improvement in symptoms.
The researchers added that, while participants' follow-up data are still being analyzed, initial changes in brain activity one day after treatment were a good predictor of whether a person would still show improvement at six months. Carhart-Harris added, “We still don't know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this.”
“We know that some people relapse, and it is possible that after a while their brains will return to the rigid patterns of activity that we see in depression,” the expert added. The authors note that, while these findings are encouraging, previous trials evaluating psilocybin for depression were conducted under controlled clinical conditions, using a controlled dose formulated in a laboratory, and included extensive psychological support before, during and after the dosage, provided by mental health professionals.
Patients with depression should not try to self-medicate with psilocybin, since taking hallucinogenic mushrooms or psilocybin in the absence of these careful precautions may not have a positive result, specialists specifically said. David Nutt, current director of the Imperial College for Psychedelic Research, stated “these findings are important because, for the first time, we discovered that psilocybin works differently than conventional antidepressants, making the brain more flexible and fluid, and less rooted in negative thinking, patterns associated with depression. This supports our initial predictions and confirms that psilocybin could be a real alternative approach to depression treatments.”
“An exciting implication of our findings is that we have discovered a fundamental mechanism through which psychedelic therapy works not only for depression, but also for other mental illnesses, such as anorexia or addiction. Now we need to test whether this is the case, and if it is, then we have found something important,” concluded Carhart-Harris.
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