How to Change Your Mind

The summary

Psychedelics do their work by quieting the brain circuit that maintains your sense of being a separate self. That circuit, the default mode network, normally filters incoming reality and keeps you running in familiar grooves of thought. When psilocybin or LSD turns it down, the brain lets in more raw sensory input and regions that usually keep to themselves begin talking to each other in new ways. Colors intensify, the boundary between you and the world softens, and the rigid mental loops that hold people inside depression or addiction can finally loosen. Brain scans back this up: the more completely that ego-maintaining network goes quiet, the more profound and therapeutically useful the experience tends to be. As one good rule of complex systems has it, a good way to understand something is to disturb it and watch what happens.

A long history, then a sudden ban

Humans have kept company with these substances for thousands of years. The Aztecs used psilocybin mushrooms and morning glory seeds, and Native American tribes used peyote, all in spiritual and healing rituals that the Roman Catholic Church later tried to stamp out as communion with the devil and a threat to Christianity. That long lineage suggests psychedelics may have shaped the very origins of religion and human consciousness. The modern chapter began in 1938, when the Swiss chemist Albert Hofmann synthesized LSD while trying to make a circulatory stimulant, then accidentally absorbed it five years later and documented its effects. Around the same time, the ethnobotanist R. Gordon Wasson introduced psilocybin mushrooms to the West through a widely read account of his experience with the Mazatec people of Mexico.

Early researchers thought LSD mimicked psychosis, which pushed them to ask whether mental illness might have a biochemical basis rather than a purely psychological one. But as subjects reported transcendence and philosophical insight alongside the occasional bad trip, the field opened up, and by the mid-1960s more than a thousand papers had been published at prestigious institutions. Then the Harvard researchers Timothy Leary and Richard Alpert, who later became Ram Dass, ran uncontrolled experiments, were dismissed, and turned into counterculture icons. Leary urged mass psychedelic use to trigger a social revolution, young people began rejecting corporate life and the draft, and President Nixon called Leary “the most dangerous man in America.” By the end of the decade the government had banned the drugs for research and recreation, driven far more by fear of social disruption than by any evidence of harm.

The renaissance, and why set and setting matter

The modern revival hinges on a single 2006 study. Neuroscientist Roland Griffiths at Johns Hopkins showed that psilocybin could reliably produce mystical experiences that subjects rated among the most personally and spiritually significant of their lives, with benefits that lasted. Griffiths reframed psychedelics as safe, non-toxic, and non-addictive when used properly, separating them from the recreational drugs they had been lumped in with, and reopened the door to rigorous, controlled research.

One hard-won lesson from the earlier era shapes all of it: set and setting. The mindset you bring and the environment you’re in can decide whether a session heals or terrifies. Modern trials happen in calm, comfortable rooms with a trained guide to steer the experience and head off a bad trip. Critics say this primes people to have mystical experiences, and researchers concede the point but argue the structure is unavoidable for safety and, anyway, aligned with the goal. The experiences themselves resist description, with people reporting that they dissolved into the universe, spoke with God, or realized death was an illusion. Pollan offers two readings: either the chemicals manufacture hallucinations, or they open perception to real things we normally filter out. Either way, the psychological effects are undeniably real.

What the brain is actually doing

The strangest implication is that ordinary waking consciousness is itself a kind of controlled hallucination, since the brain admits only the sliver of information it deems necessary for survival. Psychedelics suggest our usual way of seeing is just one setting among many. They matter clinically because there is a strong correlation between unhappiness and a hyperactive default mode network, the self-referential voice that narrates your life, judges you, and keeps you walled off from everything else. Quiet that voice and people describe “ego death”: the self dissolves, fear falls away, and what remains is connection and love. Pollan proposes that the truest antonym of “spiritual” is not “material” but “egotistical,” because when the ego dissolves, so does a narrow sense of self-interest, leaving something broader and more openhearted in its place.

Ego death and the end of suffering

That mechanism is exactly why psychedelics help people facing death. Patrick Mettes, a terminal patient in one study, went through two psilocybin sessions that let him make peace with the cycle of life and death, and in trials roughly 80 percent of terminal patients report reduced anxiety and fear of dying. The same flexibility helps with depression and addiction. A 2016 study at Imperial College London treated patients with chronic, treatment-resistant depression, and a week later 80 percent had improved and more than 60 percent were in full remission, many saying they felt newly connected to the world. As the neuroscientist Robin Carhart-Harris puts it, a happy brain is a supple, flexible brain, while depression, anxiety, and addiction are what it feels like to have a brain grown too rigid in its pathways, a brain with more order than is good for it. Psychedelics restore the plasticity that lets it rewire.

The bottom line

Psychedelics work by temporarily loosening the brain’s grip on the self, which lets rigid mental patterns dissolve and new connections form, and early clinical results show unprecedented success against depression, addiction, and the terror of dying. The remaining obstacles are regulatory and financial, not scientific. Read this if you’re curious about consciousness, skeptical of how these substances were banned, or looking for where mental health treatment may be headed next.