So-called “magic mushrooms” contain the hallucinogenic substance psilocybin. A study now shows that this fungal toxin has a long-lasting effect after a single dose: Even a month after ingestion, anatomical changes in the white matter of the brain were still evident and brain activity was more chaotic. At the same time, the test subjects were cognitively more flexible and reported an improved sense of well-being – and this increased the more intense their psychedelic trip was. The results could help to better understand the therapeutic effects of psilocybin against mental illnesses.
In Latin America, mushrooms containing psychoactive substances were used in shamanic rituals centuries ago. Psilocybin, the ingredient in these “magic mushrooms”, is converted in the body into the active form psilocin, which binds to serotonin receptors in the brain and thus triggers a psychedelic high with strong hallucinations. Because previous studies have shown positive effects on neuronal plasticity and cognitive flexibility, psilocybin is being explored as a potential therapy for mental illnesses such as depression, anxiety and addictions that do not respond to other treatments.
Drug addiction for science
“Psychedelics have strong effects on acute brain function and long-term behavior, but whether they also cause lasting functional and anatomical changes in the brain is largely unknown,” reports a team led by Taylor Lyons from Imperial College London. In order to track down such long-term changes, the researchers administered psylocibin to 28 volunteers and examined their brain function before, during and after the psychedelic high. None of the test subjects had ever used mind-altering substances before.
In the first session, volunteers received only a tiny placebo dose of one milligram of psilocybin. This dose is so low that no effect is expected. In the second session, however, the researchers administered a very high dose of 25 milligrams of psilocybin to their test subjects under controlled conditions and constant monitoring, which led to an intense psychedelic high. Before, during and after the two sessions, Lyons and her team recorded the test subjects’ brain waves using electroencephalography (EEG). They also recorded brain activity beforehand and a month later using functional magnetic resonance imaging (fMRI) and measured the brain’s connectivity using a technique called diffusion tensor imaging (DTI), which makes the neural pathways visible. They also used questionnaires and tests to assess the volunteers’ well-being, psychological insight and cognitive abilities.
Improved well-being
The result: “At a dose of 25 milligrams of psilocybin, we observed a significant increase in signal complexity in the brain – also referred to as ‘brain entropy’,” report the researchers. The signals observed in the EEG became more disordered, suggesting that the brain was processing a larger amount of information. This effect was strongest during the acute state of intoxication, but was still evident four weeks after the trip. As a result, the test subjects reported increased emotional well-being in the weeks following the psychedelic experience. They were more optimistic about the future and had the impression that they could handle problems well.
The greater the brain entropy during the trip and the more people felt they had gained new psychological insights the following day, the higher their self-reported well-being was after a month. “Our data show that such experiences of psychological insight are related to an entropic property of brain activity and that both are involved in driving subsequent improvements in mental health,” explains Lyon’s colleague Robin Carhart-Harris. “This suggests that the trip – and its analogues in the brain – is a key component of how psychedelic therapies work.”
Anatomical changes in the brain
Diffusion tensor imaging also revealed anatomical changes in the white matter four weeks after taking the 25 milligram dose. The nerve pathways were more compact and the ability to diffuse was lower. According to the researchers, it is difficult to say what effects these changes will have. “A decrease in axial diffusivity has been observed, among other things, in meditation, healthy neurological development and learning, but also in axonal injuries, the aging process and associated diseases,” they explain. Further research is needed to better understand the changes and assess their consequences.
For the test subjects, the effects seemed to be rather positive. In addition to increased well-being, they also showed greater cognitive flexibility. “Psilocybin appears to loosen entrenched patterns of brain activity and give people the ability to rethink deeply ingrained thought patterns,” says Lyons. “What is particularly exciting is the fact that these changes are accompanied by new insights and increased well-being.”
The findings could be particularly helpful for treating people with depression, anxiety disorders or addictions. “We already knew that psilocybin could be helpful in treating mental illness,” says Carhart-Harris. “But now we understand much better how it works.”
Source: Taylor Lyons (Imperial College London, UK) et al., Nature Communications, doi: 10.1038/s41467-026-71962-3