Psilocybin and Brain Medicine


Psilocybin is a chemical found in magic mushrooms that causes the user to experience a sensory overload of saturated colors and patterns. Recent research has found that this effect happens because the brain becomes “hyperconnected” and allows for increased communication between different regions. It is hoped that this ability can be manipulated in order to manufacture drugs to treat neurological conditions. The paper was published in an open access format in the Journal of the Royal Society Interface with Giovanni Petri of Italy’s ISI Foundation serving as lead author.

The chemical works by binding the same receptors in the brain as the neurotransmitter serotonin. This allows the drug to alter mood. While many people have a happy, meaningful experience, some can have a “bad trip” and experience extreme paranoia  Prior studies have found that that getting high on psilocybin doesn’t just create a colorful, psychedelic experience for a couple of hours; it can cause neurological changes that last over a year. These changes resulted in a personality that was more open to the creative arts and became happier, even 14 months after receiving the psilocybin. 

Though previous research surmised that psilocybin decreased brain activity, the current study used functional magnetic resonance imaging (fMRI) to see what was really going on. The study used 15 participants with prior positive experiences with hallucinogens to avoid a bad trip inside the enclosed machine. Some of the participants received psilocybin, while the other half received a saline placebo.

Simplified illustration of the connections tracked while receiving the placebo (a) and the psilocybin (b). Image credit: Petri et al., 2014.

Surprisingly, the researchers saw that upon receiving psilocybin, the brain actually re-organized connections and linked previously unconnected regions of the brain. These connections were not random, but appeared very organized and stable. Once the drug wore off, the connections returned to normal.

“We can speculate on the implications of such an organization. One possible by-product of this greater communication across the whole brain is the phenomenon of synesthesia which is often reported in conjunction with the psychedelic state,” the authors wrote.

Synesthesia is a subconscious pairing of two things, like colors and numbers. Someone experiencing this phenomenon might always view the number 2 as green or read 6 and think of the color purple. Because of these strange associations, individuals taking psilocybin likely have poor color perception, despite being inundated with the hallucinogenic colors.

The mechanism of how psilocybin is creating these changes is not yet known and will require further study. The researchers believe that in understanding the drug’s mechanism for temporarily re-wiring the brain and altering mood, it could potentially be manipulated into making a functional treatment for depression or other disorders. However, there is much more to be learned before it can be used in that manner.


There was a participant in the study who had had an extensive, extensive practice, like tens of thousands of hours of meditation, which is an incredibly extreme amount,” said Frederick Barrett, PhD at the Johns Hopkins Department of Psychiatry and Behavioral Sciences. “And she indicated after her psilocybin session that she relived all of the peak experiences she had ever had meditating. Wow.”

Barrett is currently studying the effects of psilocybin on the brains of long-term meditators, specifically default mode network functional connectivity and retrospective ratings of qualitative experience. It includes a set of experimental sessions separated by two-month buffers. The first two are split between psilocybin and placebos—participants who receive placebos are switched to psilocybin at later stages. Before and after the drugs are administered, participants get MRI scans to measure brain activity.

“We have a target of 40 people that we’re looking to enroll in the first portion of the study,” said Barrett. “And we actually just got finished screening the 40th person. So, they’re not completely enrolled yet, but we suspect we may have finally completed this study after three and a half years.”

Any study such as this poses certain difficulties. Funding must come from somewhere. In this case, Bill Linton, through the Heffter Research Institute, has generously kicked in. (Heffter, the Beckley Foundation, and MAPS have been the major benefactors of psychedelic research in the US and Europe for many years.) Regulatory hurdles are not insignificant—the research needs FDA approval under an Investigational New Drug application, and someone on the team needs a license to dispense Schedule 1 drugs. That would be Dr. Roland Griffiths, a mentor to Barrett and a drug researcher with decades of experience.

Then, there is the challenge of recruitment. “It was exceptionally difficult because we were really looking for a bit of a unicorn in terms of the participants for the study. So we were searching far and wide for individuals who had an established Buddhist meditation practice who were open to using or experiencing the effects of a psychedelic drug, but who hadn’t already done so within the context of their practice.”

Fred Barrett talks “Psilocybin, Meditation, Mystical Experiences, and the Brain” at Horizons Perspectives on Psychedelics 2015.

The fifth precept of Buddhism, as generally translated, forbids intoxication to the point of heedlessness. “There were some Buddhist teachers who, upon hearing and contemplating our study, said, ‘this is against my religion,’ to the extent that a Buddhist would ever say that. And, thankfully, there were others, the people who were good candidates for the study, who interpreted it much differently. That it’s just meant to say, ‘don’t do anything that will dim your awareness.’”

The threshold for what constitutes long-term meditators in this context is a fairly high one. Participants are required to have a daily practice sustained for at least three years. This could mean a 20-minute practice, provided there are no breaks, but usually means more serious dedication, including long retreats. “We calculated the average lifetime hours of meditation that were represented in the study was roughly 5,000,” said Barrett. “Hours and hours of meditation.”



Likewise, the doses of psilocybin administered are not low. While he can’t share exact dosages, Barrett provides an illustration. “We administer the drug in one location, in our research laboratory where we’ve done all of our synthesizing studies,” said Barrett. “An hour after drug administration, when they’re beginning to feel the effect of the drug, we get them in a car and drive them ten minutes across town to the imaging center… Of the 20 people who completed that portion of the study, 18 of them experienced the onset of drug effects before leaving to go to the imaging center. And each of the 18 people, when the hour was up and we were ready to get in the car, we asked, ‘Hey, how are you? Are you ready to go?’ And each of them hesitated a just a bit, and they’re, like, ‘Okay, you know, I guess I came here to do this, and we’re here, so I’m going to be a good subject,’ and we get in the car. But there was a substantial drug effect.”

Barrett has not yet fully immersed himself in the data emerging from this work, but as he presents his preliminary findings, the implications are clear. “There are a number of cases where descriptions of psychedelic drug experiences dovetail with descriptions of non-drug mystical, profound, or otherwise nominally psychedelic experiences,” he said. “A motivation of this research is to first ask the question of whether these things really are similar, to which many of our meditators have answered quite clearly, yes. A further motivation is to at least begin to reconcile the notion that, on one hand, you have a pharmacological, and on the other hand, a non-pharmacological route to the same space. Understanding the space that these two routes can bring us to, and understanding the neurobiological basis for these states, may help us to begin to better understand the biological basis of consciousness.”

Instruments such as the MRI can detect patterns in states achieved through different means, and may break down some of the barriers that impede objective understanding of subjective experiences. “Naturalistic research allows us a window into the experiences and practices of many traditions of consciousness alteration,” said Barrett. “Psychedelics allow us a reversible and somewhat controllable tool to peer into consciousness alteration. I see this and research on other traditions of consciousness alterations to be very complementary.”





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