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Psilocybin Works Like Magic in the Brain

The Collective Voice on May 29, 2023

Exactly what psilocybin does to the brain to trigger changes in mood and behavior is still a big mystery, but we know that, acutely, when someone’s on a psychedelic, the brain communicates in a much different way than it was “programmed” to, says Michael McGee, MD, staff psychiatrist at Atascadero State Hospital in California and author of The Joy of Recovery. He explains that the programming begins in mid to late childhood to handle the roughly 90 to 100 billion neurons in the cerebral cortex, the outermost layer of the brain that plays a key role in higher-order functions such as perception, thought, memory, and judgment. “If all of those neurons could communicate with each other, the number of potential connections is probably higher than the number of atoms in the universe,” says Dr. McGee.

But the brain can’t function like that—it has to be efficient for its survival. “So there’s a pruning process, where perceptions of the way we understand ourselves in the world are narrowed, and the ego-consciousness develops,” explains Dr. McGee. “And what happens to all of those neural connections is that some get prioritized and are very efficient, like highways with a lot of neural traffic going through, and the others are paired down and rarely used, like dirt roads.” That’s where psilocybin can come into play—it can basically open up those dirt roads again and send a lot more traffic down them.

“Psilocybin and other psychedelics that are serotonin HT2A receptor agonists or stimulators massively increase brain entropy, so you have all of the neurons talking to each other in a very open, non-focused, and less organized way,” Dr. McGee says. At the same time, he says, there’s a reduction of activity in the Default Mode Network (DMN), a network of interacting brain regions that’s active when you’re not focused on the outside world. In other words, an inhibited DMN means there’s less of that stream of self-reflective thought going on that we associate with our independent thinking self.

“When that goes away, and it’s combined with all of these novel neural connections, the brain is capable of making radically different associations and developing new understandings of reality,” says Dr. McGee. For instance, if the operating paradigm of the brain is trauma-based and defines others and the world as “bad” and “unsafe,” it could be replaced with a larger paradigm of “goodness” (or at least a less rigid experience of negativity) that sees the essence of the universe as love, and thus produces more feelings of love and compassion.

Animal studies also suggest that psychedelic drugs, like ketamine, can prompt the growth of new neurons and branch between dendrites, the parts of brain cells that reach out and communicate with other brain cells, Johnson says “It could be that these types of changes are unfolding in the days and weeks following a psilocybin session, and they represent a kind of fluidity and plasticity in the system,” he explains. “It’s like a plastic that’s been heated and becomes malleable enough to reshape. Eventually, it’s going to cool down, but you’ve established a new normal during this time.”

Big picture, Johnson suspects that the drug is augmenting the process of how people change their behavior by increasing their sense of openness, which could lead to a future world with less depression, anxiety, and addiction. “In all of the disorders we’re studying, you’re essentially talking about people who are stuck in a very narrow mental and behavioral repertoire, and it’s very hard to get out once you’re there,” says Johnson. “There are so many self-reinforcing properties—more negative thinking leads to less social interaction and then more focus on the addictive substance—and it’s that ‘stuckness’ that really seems to be affected by psychedelic experiences. They seem to supply clarity and mental flexibility that allows people to jump outside their patterns.”