Psychedelic drugs—and the fear thereof—have shaped culture, politics, and economics with a surprising magnitude. After half a century of being confined to the underground, these substances are making a comeback. Best-selling author and journalist Michael Pollan delves into the mushrooming world of psychedelic research, uncovering the history and surprising benefits of LSD and psilocybin through research, interviews, and some first-hand exposure.

During the mid-twentieth century, two compounds of similar chemical composition were discovered that have left an indelible impression on Western society.

Lysergic acid diethylamide, or LSD, was discovered in a laboratory in 1938, just months before the fission of the first uranium atom. Originally developed in an attempt to aid circulation, LSD’s creator discovered its psychedelic potential years later when he accidently ingested a small amount of the substance.

The other “discovery” was a small, brown mushroom known as psilocybin. For thousands of years, indigenous peoples in Central America incorporated these magic mushrooms in their ceremonies, but in 1955, just over a decade after the discovery of LSD, a team of Americans sampled the fungus in Oaxaca, Mexico, which led to magazine publications about “mushrooms that cause strange visions.”

The influence that these compounds have exerted on economics, politics, and society is deceptively strong. It is inseparably linked to the counterculture’s ascendency. The 1960s youth made the “acid trip” a rite of passage. Trips gone sideways, a string of drug-related deaths, and breakdowns garnered bad press. The public’s wrath eventually died down, but suspicion and aversion remained the nation’s tenor on the drug matter. Richard Nixon considered fired Harvard psychologist and LSD advocate Timothy Leary the most dangerous man in America. He declared war on drugs. The debate seemed largely settled as far as the public was concerned, so psychedelics went underground with the counterculture.

These substances were housed in laboratories before they ever found their way into VW vans and drum circles. In the 1950s, research involving LSD led to the discovery of neurotransmitters and that some mental conditions were not merely psychological but neurological. Psychedelics were being brought into therapy practices to address issues of addiction, anxiety, and depression.

After decades of simmering suspicion, psychedelics are making a comeback. We are starting to see cracks in the War on Drugs edifice. 2006 was a momentous year for those dedicated researchers and “psychonauts” who were keeping an ear to the ground for rumblings of change.

One event was the centennial of Albert Hoffman’s birth. Hoffman developed LSD in the late 1930s and discovered its psychedelic qualities in 1943. What made this symposium in Basel, Switzerland, singular was that Hoffman was in attendance. After 100 years, he was still lucid and spry. There was a hushed, almost worshipful reverence as a crowd of about 3,000 neuroscientists, therapists, journalists, mystics, and scholars watched the five-foot-nothing man express optimism about the future of psychedelics, that they would become part of a recognized field of study. Everyone present sensed a change in the wind.

The second major event of 2006 came just weeks later when the U.S. Supreme Court upheld a decision to protect the religious rights of the loosely Christian new religious movement, União do Vegetal (UDV), which uses the plant-based psychedelic substance in its rituals. The decision pertained specifically to the provincial scope of religion, but it set a precedent, a crack that could be widened.

Thirdly, and most significantly, a Johns Hopkins research team published a research paper with Psychopharmacology documenting the positive mystical effects that psilocybin can induce. Roland Griffiths, a heavyweight in the scientific community, headed up a team of researchers at Johns Hopkins. He developed a study involving 30 subjects who had never been exposed to psychedelic substances. Half were given psilocybin, the other half, placebos. Of those who were given psilocybin, two-thirds considered it one of their most significant spiritual experiences, and a third considered it their number one spiritual moment that they’d had to date. Over a year later, those numbers had declined only slightly, and most reported significant, lasting improvements in perspective and quality of life.

If you’re like most people, you missed all this, or at least did not see any connection between these events. To those who were looking for this, such developments were exciting watershed moments to be built upon.

So what is actually happening in the brain when someone trips?

One of the most noticeable changes is in the brain’s default mode network, or DMN. The DMN is like your mental screensaver. When you don’t have a task that requires your attention or mental energy, the DMN takes over. When you daydream, brood over your mistakes, fret about the future, compare yourself to others, focus on mental constructions like ego, your DMN is firing instead of your attentional networks. It’s also been called “the me network,” a reference to the fact that self is always the point of orientation. The DMN flits and wanders, which manifests as an unhealthy self-obsession. The landmark paper “A Wandering Mind Is an Unhappy Mind” gets at this same point.

This is where psychedelics have proven helpful in clinical trials: they dampen the raging default mode network. When the DMN was the quietest, subjects were most likely to experience ego dissolution. Many reported that sense of discrete self gave way to a connection with surroundings. Seasoned meditators report similar experiences, and fMRIs reveal that their default networks are barely active. Studies have found similar dynamics at play in people engaged in prayer, fasting, and deep breathing exercises. By taking the brain off the default mode network, people experience heightened consciousness and even ecstasy.

When the ego is oppressively present, we come unyielding in our preferences and viewpoints. This inflexibility can be damaging to relationships and to societies more generally. Psychedelics have a way of helping people think beyond their preconceived mental hierarchies and unlock the box of conventional thinking.

Interestingly, when people’s DMN’s are dampened through careful exposure to psychedelics, they also tend to feel more connected to nature.

Psychedelics tend to induce a high-entropy state. The brain becomes less regimented in its assigned roles. The various parts become more integrated and interrelated. One researcher describes it as network lines communicating more openly. Psilocybin stimulates connections between regions of the brain that are generally never connected. The areas of connection and multitude of connections mean a flow of information that far exceeds that of usual waking consciousness.

The new pathways sometimes lead to synesthesia, where normal sensory connections get crossed, and people are able to associate sounds with tastes and colors. With information moving through unexplored pathways, people encounter more vibrant and creative thought.

The entropic brain also delivers a form of consciousness that small children experience. UC Berkeley professor Alison Gopnik distinguishes between the spotlight consciousness of adults and lantern consciousness of children. Spotlight consciousness (also called ego consciousness) focuses on one particular entity or subject at a time whereas children’s lantern consciousness shines light on everything in their field of sight.

This lantern lighting is what supports that characteristic sense of wonder that most of us lose at some point in adolescence. In effect, babies and children experience a constant, milder trip. Children have a lot to teach us about higher forms of consciousness.

Phrases like “mind expansion” might seem stale and passé, but neuroscience provides ample evidence that the trope actually hits the mark.

The first person to suggest administering psychedelics to the terminally ill was not a scientist or psychologist, but the writer Aldous Huxley. He actually asked his wife to give him a shot of LSD when he was on his deathbed in 1963. Huxley saw LSD as a way of providing a portal to self-transcendence that alleviates the fear of death in those final moments.

NYU and Johns Hopkins have conducted tests on terminally ill cancer patients to see how they would respond to psilocybin. They found that 80 percent of participants experienced a dramatic reduction in anxiety and depression and those results held for at least six months. The more intense the mystical experience, the more lasting and profound the impact tended to be. These studies were small, involving fewer than 100 patients, but the results are promising.

Psychedelics have also proven helpful in cases of addiction. Native Americans have used the psychedelic cactus fruit peyote for ritualistic purposes as well as for treating alcohol addiction. Tests in the 1950s and 1960s were not well-designed, but recent studies have yielded encouraging results in their small samples. The University of Mexico created a study to observe how ten alcoholics who had been unresponsive to conventional therapy responded to psilocybin. Researchers observed sustained decreased drinking even 36 weeks after the experience.

In the case of addiction and depression, the value of psilocybin and other psychedelics is that they expand an intensely contracted vision of the world. The addict views the world in terms of his vice; the depressed individual in terms of her perceived inadequacy. Once again, the ego, which necessarily narrows scope by insisting on attention and gratification, is overcome—even dissolved—by the vibrant presentation of an alternative. An important question that the famous rat park experiment draws out is, “Do you view life as a prison or a playground?” If the person is suddenly able to see life in radically different, more positive terms, it becomes far more likely that the mind can change.

In spring of 2017, the Multidisciplinary Association for Psychedelic Studies (MAPS) gathered in Oakland, California to revisit their shared vision of restoring the cultural and academic legitimacy to the study and use of psychedelics. In the days of its founding over three decades ago, the gathering consisted of a small group of rogue scholars. At its most recent meeting, a 3,000-strong group of scholars, researchers, psychiatrists, mediums, and shamans met to discuss the future of psychedelics. The atmosphere was charged with enthusiasm and optimism.

The future is bright, but precarious. Among the notables present at the conference was plenary speaker Tom Insel, the former head of the National Institute of Mental Health. When the conference’s moderator asked the plenary panel what advice they’d give to those present, his response was quick and curt: “Don’t screw it up!” Everyone remembered Timothy Leary, the Harvard professor disgracefully fired from Harvard in 1963 for sketchy psychedelic experiments involving students. The damage he did to the field of psychedelic research was incalculable. Even as psilocybin and LSD starts to reemerge as a plausible solution to addiction, the hard, careful work of scientists, neurologists, and therapists to rehabilitate a field’s reputation can be undone through carelessness or a trial test gone horribly wrong.

Still, the potential to help not just the sick, but everyone, is considerable. To make the research more palatable and sidestep associations with hippies and anarchy, some scientists refer to psychedelics as entheogens—derived from the Greek for “the divine within.” Baggage notwithstanding,  “psychedelic” still captures it best. It literally means “mind-manifesting,” which captures what these compounds are capable of doing.

In a culture afraid of death, mistrustful of transcendence, and leery of the unknown, is it possible that psychedelics are too unpredictable to be absorbed into our institutions? The establishment prefers to mediate intellectual and religious truth, but psychedelics offer an opportunity for a mystical experience that would effectively bypass the middlemen. Time will tell how these elements will interact.