Scientists are pulling back the curtain on the mysterious mechanism behind magic mushrooms’ therapeutic effects. Tripping on psilocybin — the psychedelic compound found in shrooms — triggers widespread changes in the brain, some of which can last for weeks, according to new human research.
During a trip, neuron networks involved in intra-brain communication, memory, sense of space, time, and self become “desynchronized” in a swirl of abnormal activity, as shown in the study published July 17 in the journal Nature. Further, the level of changes in these neuronal systems corresponds with the intensity of a psychedelic experience, and though most of the brain returns to baseline within hours, some small changes persist for three weeks, per the research.
Previous clinical studies have demonstrated that psilocybin can offer long-term reprieve from symptoms for people with depression, help those struggling with addiction, and even relieve end-of-life anxiety for people with terminal illnesses. Research in animal and petri dish models have shown that the fungal compound seems to induce neuroplasticity, or flexibility in neurons, allowing for strong, potentially detrimental connections to separate and for new ones to form.
However, there’s been very little research actually showing the mechanisms by which psilocybin acts on human brains in real time, if longer-term effects unfold, and how they do. The new study fills a gap, illuminating how psilocybin alters multiple brain regions during and in the aftermath of a trip. Neuroscientists recruited seven healthy volunteers to take large doses of psilocybin as well as the ADHD medication and stimulant Ritalin 1 to 2 weeks apart. Ritalin acted as a comparison and control so the researchers could more accurately assess the specific effects of psilocybin and rule out the placebo effect. Study participants underwent an average of 18 total functional MRI scans before, during, and after their drug doses where the researchers collected data on brain activity. They also rated their subjective trip experience by answering a 30-part questionnaire. Four of the participants returned 6 to12 months later to repeat the experiment.
The repeated and detailed brain scans revealed that, during a trip, psilocybin jumbles up functional connectivity throughout the brain, causing three times as much disruption as Ritalin. Usually, neurons all across the brain fire in a synchronized pattern over the course of day-to-day life. Yet on shrooms, neurons break free from those well-trod partnerships and paths and begin to fire seemingly at random. The strongest changes were in the so-called “default mode network,” an interconnected system of brain regions known to be most active when someone is awake but restful, not focused on all that much (i.e. daydreaming or letting their mind wander). The default mode network involves the hippocampus, a critical brain region for memory, and is also thought to relate to sense of self, and perceptions of space and time.
The observed effects of a trip in progress are so profound that the unique signatures of individuals’ brain waves become unrecognizable while under the influence of psilocybin. In short: People tripping on mushrooms all display brain activity more similar to each other than to their sober selves, according to the study. “Individuality is temporarily wiped out,” said co-senior study author Nico U. Dosenbach, a neurology professor and physician at Washington University, in a press statement. “This verifies, at a neuroscientific level, what people say about losing their sense of self during a trip.”
Immediately following a trip, most of these dramatic changes disappear as the brain returns to baseline. But, crucially, a small number of pinpoint alterations in the hippocampus appear to persist. Follow-up scans showed that these tiny shifts stuck around for at least three weeks, though they were gone by the 6-12 month follow-up for the four returning participants.
“There’s a massive effect initially, and when it’s gone, a pinpoint effect remains,” said Dosenbach. “That’s exactly what you’d want to see for a potential medicine. You wouldn’t want people’s brain networks to be obliterated for days, but you also wouldn’t want everything to snap back to the way it was immediately. You want an effect that lasts long enough to make a difference.”
Dosenbach and his colleagues also tested how participants responded to a simple audio-visual task before, during, and after the drug treatment. They found that participants were mostly able to complete the task correctly (with about 80 percent accuracy) while tripping, but that while engaged in the task, abnormal brain activity lessened. This provides some of the first scientific support for the concept of “grounding,” or focusing on a task or real sensation to lessen the severity and intensity of a trip gone wrong. It also bolsters the anecdotal evidence that psychedelic experiences are context-dependent — what you do during a trip influences how the trip goes and potentially its lingering impact.
Notably, the study did not include participants with depression or any other mental health diagnosis. To definitively link the observed neural changes with previously documented therapeutic benefits, future research will need to study the brain response of people with depression.
Still, these findings are a significant step towards improving psilocybin therapy. The study offers additional strong evidence that psilocybin can spur lasting impacts in areas of the brain relevant to depression. By understanding how different peoples’ brains respond to psychedelics and the mechanism of treatment, clinicians could better judge who might be helped by the drugs. And through learning how long changes last at the neural level and how to mediate the intensity of a trip, mental health providers can create better treatment regimes and minimize potentially negative outcomes.
The new research “has clear clinical implications,” wrote Petros Petridis, a psychiatrist and professor at New York University, in a commentary published alongside the study. Petridis was not involved in the study, but noted that the findings indicate “psilocybin could make connections in the brain more malleable, which could be beneficial for people who experience rigid maladaptive patterns of thought and behavior,” such as in addiction or depression.
Alongside therapy, he wrote “psilocybin could open the door to change.”
