Single psilocybin dose linked to lasting brain and mood changes

Researchers at UC San Francisco and Imperial College London have shown that a single dose of psilocybin, the psychedelic compound found in magic mushrooms, causes likely anatomical brain changes that last for up to a month after the experience.  

The study, published May 5 in Nature Communications, was done in healthy volunteers who had never taken a psychedelic, but it may help explain psilocybin's therapeutic effects on conditions like depression, anxiety, and addiction. The researchers link temporary shifts in brain "entropy" - which is the diversity of neural activity occurring in the brain - to insight. This suggests the psychedelic trip itself is important to the drug's longer term therapeutic effects. 

The researchers found that a high dose of psilocybin led to increased entropy in the minutes and hours after taking the drug. The degree of entropy predicted how much insight, or emotional self-awareness, the participants felt the next day; and this, in turn, forecasted improvements in their sense of well-being a month later. 

Psychedelic means 'psyche-revealing,' or making the psyche visible. Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health. It suggests that the trip - and its correlates in the brain - is a key component of how psychedelic therapy works." 

Robin Carhart-Harris, PhD, senior author, the Ralph Metzner Distinguished Professor of Neurology at UCSF

A careful assessment of psilocybin's effects 

Researchers used an assortment of brain imaging and brain measurement techniques, some of which was done during the peak of the psychedelic experience, as well as before and one-month after.  

None of the 28 people in the study had a diagnosed mental health condition, which gave the scientists greater freedom to do more testing.  

In the first part of the experiment, the subjects were given a 1 mg dose of psilocybin, which the researchers regarded as a placebo, and then monitored with electroencephalography (EEG), which records brain activity from electrodes on the scalp.  

Over the next few weeks, the researchers measured their subjects' psychological insight, well-being and cognitive ability. They examined brain activity with functional MRI (fMRI) and brain connectivity with diffusion tensor imaging (DTI).  

One month after the placebo, the subjects were given 25 mg of psilocybin, a dose capable of eliciting a strong psychedelic trip. During the experience, researchers again measured the subjects' brain activity with EEG, and in the following weeks they repeated the same tests they had given after the 1 mg dose.  

This enabled the scientists to compare the effects of the psychedelic trip on the brain and mind to the effects of the placebo. 

Greater 'information' in the brain after psilocybin  

Within 60 minutes of taking the 25 mg dose of psilocybin, EEG revealed higher entropy, suggesting that the brain was processing a richer body of information under the psychedelic. 

A month later, the researchers looked at their subjects' brains with DTI, which measures the diffusion of water along neural tracts in the brain, and found that they were denser and had more integrity. This is the opposite of what happens in aging, which makes these tracts more diffuse. 

The researchers cautioned that more work needs to be done to better understand the meaning of this change, but the result is a never-before-seen sign of how psychedelics can change the brain.  

Enduring improvements in well-being 

The day after the 25 mg dose, all but one of the 28 subjects rated the trip as the "single most" unusual state of consciousness they had ever experienced. The remaining person rated it as among the top five.  

The people in the study also said they had experienced more psychological insight after taking the 25 mg of psilocybin than they had after the 1 mg placebo.  

The subjects reported increased well-being two and four weeks after the study. This was measured from responses to statements like, "I've been feeling optimistic about the future" and "I've been dealing with problems well." A month after the study they also did better on a test of cognitive flexibility.   

"Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought," said Taylor Lyons, PhD, a research associate at Imperial College London and the first author of the paper. "The fact that these changes track with insight and improved well‑being is especially exciting." 

A freer brain and a healthier mind? 

The scientists found that the subjects who had experienced the largest increases in brain entropy in the minutes to hours after taking psilocybin were the most likely to have increased insight the next day and increased well-being a month later. They concluded that improved well-being was driven by the experience of insight.  

The findings could improve treatment for people with mental illness with psilocybin, for example, by ensuring that the right dosage is used to produce the right amount of brain entropy to promote insight. 

"We already knew psilocybin could be helpful for treating mental illness," Carhart-Harris said. "But now we have a much better understanding of how."