Studies suggest that the psychedelic substance psilocybin from magic mushrooms could be helpful in therapy for depression. Evaluations of brain scans now show how the drug affects the brain of depressed people. Accordingly, it promotes the networking between different brain regions. The effect can still be observed weeks after ingestion. This could help those affected to break through deadlocked thought patterns and become cognitively more flexible again – provided they receive adequate therapeutic support. The researchers warn against attempts at self-medication.
In addition to a lack of joy and motivation, those who suffer from depression often have a so-called “negative cognitive distortion”, which is characterized by pessimism, low mental flexibility, rigid thought patterns and negative fixations on “the self” and the future. Many antidepressants are based on inhibiting the reuptake of the neurotransmitter serotonin and thus ensuring that this “happy hormone” remains available in the patient’s brain for longer. However, some patients hardly respond to these selective serotonin reuptake inhibitors (SSRIs). Her depression is considered treatment-resistant.
Party drug as an antidepressant?
A team led by Richard Daws from Imperial College London has now investigated a possible alternative therapy for such patients: the hallucinogenic fungal toxin psilocybin, which is used as a party drug in the form of magic mushrooms. “Previous studies have shown that psilocybin has antidepressant potential, but how exactly it works therapeutically is not well understood,” the authors explain. “We therefore evaluated two clinical studies on psilocybin against depression to see what effect the substance has on the brain.”
The two analyzed studies included a total of 59 depressed patients, from whom brain scans were recorded before, during and after the controlled intake of psilocybin. In the first study, all 16 patients who participated received psilocybin; in the second study, 22 of 43 patients received psilocybin, with the remainder receiving the conventional antidepressant escitalopram, although neither subjects nor caregivers knew who was in which group. All subjects were accompanied psychotherapeutically.
Psychedelic trip increases mental flexibility
The results of the two studies support the thesis that psilocybin can help against depression when taken in a controlled, accompanied manner. Compared to the selective serotonin reuptake inhibitor escitalopram, the psychedelic led to a greater improvement in patients’ depressive symptoms, the research found. But what is the mechanism behind it? To find out, Daws and his colleagues took a close look at the brain scans taken as part of the two studies.
“In both studies, the antidepressant response to psilocybin correlated with increased connectivity between different brain regions,” the authors report. Previously, people who had their brains scanned during a magic mushroom trip had shown greater brain connectivity. “Here we see the effect weeks after treatment, which suggests transmission of the acute drug effect,” says Daws colleague Robin Carhart-Harris. In the case of escitalopram, on the other hand, no change in the brain networks could be observed.
Self Medication Warning
“Apparently, psilocybin works differently than traditional antidepressants,” says Daw’s colleague David Nutt. “It makes the brain more flexible and less locked into the negative thought patterns that accompany depression. This supports our initial predictions and confirms that psilocybin may be a viable alternative approach to the treatment of depression.” Taking just a few doses could potentially lead to long-term improvement if the psychedelic experience is supervised and monitored by qualified therapists.
The authors warn against trying it on yourself. “While the results are encouraging, the studies took place in controlled clinical settings, with a fixed dose and comprehensive psychological support,” they explain. “Patients with depression should not attempt to self-medicate with psilocybin, as taking magic mushrooms or psilocybin may have less beneficial effects without these careful safety precautions.” Further studies in larger groups of patients are also needed to determine efficacy and safety clear enough of psilocybin. Only if these tests are successful can the fungal drug possibly find its way into clinical practice.
Source: Richard Daws (Imperial College London) et al., Nature Medicine, doi: 10.1038/s41591-022-01744-z