If you’ve heard anything lately about the use of psychedelic drugs and their potential to address all manner of mental illness, you can thank Harvard University and University of California, Berkeley Professor Michael Pollan.
How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence (2018) tells the history of two distinct waves of psychedelic drug research. In the middle of the twentieth century, numerous studies were beginning to reveal an entirely novel approach to treating mental disorders and also raised questions about the very nature of human consciousness. “For most of the 1950s and early 1960s,” Pollan tells us, “many in the psychiatric establishment regarded LSD [‘acid’] and psilocybin [active ingredient in ‘magic mushrooms’] as miracle drugs.”
So promising were the possibilities, Sandoz—a pharmaceutical company hoping to discover commercial uses for LSD— “offered to supply, free of charge, however much LSD any researcher requested. The company defined the term ‘researcher’ liberally enough to include any therapist who promised to write up his or her clinical observations. This policy remained more or less unchanged from 1949 to 1966 and was in large part responsible for setting off the first wave of psychedelic research…”
By 1966, tens of thousands of patients had been administered psychedelic drugs during government approved and funded clinical trials. Many clinicians used readily available LSD during therapy sessions. Southern California, seemingly always on the cutting edge of socio-cultural developments, was home to a number of psychiatrists and psychologists who catered to the stars. Celebrities undergoing psychedelic drug therapy included Jack Nicholson, Stanley Kubrick, James Coburn, and Cary Grant.
In 1959, following several psychedelic therapy sessions, Cary Grant reported during an interview that he felt as if he had been “born again.”
“A 1967 review article summarizing papers about psychedelic therapy published between 1953 and 1965,” Pollan writes, “estimated that the technique’s rate of success ranged from 70 percent in cases of anxiety neurosis, 62 percent for depression, and 42 percent for obsessive-compulsive disorder.” Other studies revealed astounding rates of success with alcohol and tobacco addiction.
As LSD became widely used by young people during the counterculture revolution of the 1960s, psychedelic drugs came to be seen as just another dangerous and addictive substance, like heroin and marijuana, which was contributing to the deterioration of American society. One of the scientists studying these drugs was clinical psychologist Timothy Leary who founded the Harvard Psilocybin Project in 1960. Leary became an outspoken advocate for the use of these drugs, not only for the treatment of mental disorders, but also for the spiritual development of otherwise healthy humans. It is not difficult to understand the appeal for young people; especially as the Vietnam War was broadcast daily into living rooms and cities began to burn during several long, hot summers of racial discord. Leary’s message to young people did nothing to assuage the fears of their parents. “Turn on, tune in, drop out,” Leary advised.
Unfortunately, LSD became associated with all that ailed America and many today blame Leary for promoting the drug outside of a clinical setting. As we discover in Pollan’s book, taking LSD and other psychedelic drugs without a guide or therapist can have devastating consequences and many of these negative stories shaped the narrative over psychedelic drugs.
The conservative backlash was swift and furious; culminating in the Controlled Substances Act of 1970, which classified psychedelics as Schedule 1, meaning the promising and potentially transformative research into these mysterious molecules was shut down, and kicked off the disastrous War on Drugs.
After psychedelic therapy and research was driven underground by the Controlled Substances Act, it seems to have re-emerged in the 1990s, despite no change in the law. Today, we find ourselves amid a “psychedelic renaissance” and Michael Pollan traces the emergence of this phenomenon by zeroing in on three events that all occurred in 2006.
In this detailed historical account, Pollan describes the celebration of the centennial of the 1906 birth of Albert Hofmann, who had accidentally discovered LSD in 1943. Amazingly, centenarian Hofmann was still alive to be personally honored at a three-day symposium: “LSD — Problem Child and Wonder Drug,” held in Basel, Switzerland. In attendance, as Pollan writes, were “[t]wo hundred journalists, along with more than a thousand healers, seekers, mystics, psychiatrists, pharmacologists, consciousness researchers, and neuroscientists, most of them people whose lives had been profoundly altered by the remarkable molecule that this man had derived from a fungus half a century before.”
In that same year, the Supreme Court ruled that the federal government could not prohibit the UDV (a Native American church called Union of the Plants) from using Ayahuasca in their religious ceremonies. The third event Pollan identifies is a 2006 publication in Psychopharmacology titled “Psilocybin Can Occasion Mystical-Type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance” written by Roland Griffiths who Pollan describes as a “rigorous and highly regarded scientist.”
Unlike “the more common drugs of abuse, with their demonstrated toxicity and potential for addiction,” as Pollan writes, Griffiths posited that psilocybin and other psychedelics should be treated differently. The abuse and addiction symptoms of alcohol, or cocaine, or heroin simply do not apply because something else is afoot. One researcher, using LSD to treat alcoholism reported that “we considered not the chemical, but the experience as a key factor in therapy.” Pollan adds, “This novel idea would become a central tenet of psychedelic therapy.”
In my understanding, Pollan is saying, with a great deal of credible anecdotal evidence to back him up, that psychedelic drugs do not distort reality, they reveal it. One commentator to the Griffiths psilocybin paper wrote that psychedelics had the potential to “free oneself of the bounds of everyday perception and thought in a search for universal truths and enlightenment… even if they sometimes involve claims about ultimate realities outside the purview of science.”
This illustrates one of the huge obstacles faced by those conducting psychedelic drug research; evidence of their efficacy is often reported anecdotally and is very difficult to quantify. In order to study psychedelics, Pollan puts forth, typically demanding drug trials might need to move beyond the traditionally measured effectiveness of a drug in order to establish standards of care and safety. In other words, psychedelic research might better be explored in conjunction with spiritualists, anthropologists, and philosophers, who have historically pondered the questions that arise in the study and use of psychedelic drugs.
As far as I understand it, and as simply as I can put it; most psychedelic drugs attach to the same receptor in the brain and, instead of adding a chemical that blurs reality, the effect is a sort of shedding of the ego, or sense of self. The result is that many who undergo psychedelic therapy have reported seeing themselves not as an individual but rather, as a part of the larger whole; not just of society, but of the entire world or universe. Sounds kinda trippy, I know… but Pollan lands this trippy thinking squarely on the spot labeled “plausible.”
Some of these scientists believe that this shedding of the ego unblocks brain pathways that have been blocked over time… blocked rationally, however, as a means of survival and protection of the “self.” This unblocking, though, while making patients extremely vulnerable, opens up brain pathways re-connecting parts of the brain that had been disconnected through years of rigid thinking and experience… with the ego in charge. Indeed, some reports compare the effects of a trip to re-establishing the brain of a young child, not yet managed by the ego, and seeing things, as if for the first time, and thus, in awe of them.
For those of you who have tried some of these psychedelics, it is important to note that unprepared users who have no therapeutic guide during their trip are unlikely to experience the therapeutic effects described by so many. It is only with conscientious effort in a controlled setting that therapy seems to produce potentially positive and sustainable results
For instance, it is accepted very broadly that psychedelic therapy is most productive when “set” and “setting” are studied and managed. “Set” is the psychological state of mind of the person using psychedelics while the “setting” is the physical environment in which the dosing experience takes place.
While quantifiable results are difficult to come by in psychedelic research studies, many standard practices have come to define the most effective uses of these mysterious drugs. The drug researchers—most of whom have tried the psychedelic drug they are studying—break this therapy into three different phases. First, there is a great deal of preparation for what to expect. Most fascinating is that patients are taught techniques that assist them in taking charge of the psychedelic trip. This preparation includes taking on the challenges that occur during the trip. For instance, if a door appears, open it; if a stairway appears, climb it. Patients are also prepared for dealing with fearful things that might occur (in the mind) and to confront those as well; perhaps facing down a threatening figure and asking “Why are you here? What relevance do you have to my memories, experiences?”
The second phase is that the dosing experience itself is overseen by a trained psychedelic therapist who is present during the entire trip. The “psychonaut” must understand that, despite what might occur—like a “bad trip”—they are physically safe. If the psychonaut ventures to scary places in his mind, the therapist is there to facilitate, reminding the psychonaut of the “purposes” of the trip.
Pollan writes: “As the literary theorists would say, the psychedelic experience is highly ‘constructed.’ If you are told you will have a spiritual experience, chances are pretty good that you will, and, likewise, if you are told the drug may drive you temporarily insane, or acquaint you with the collective unconscious, or help you access ‘cosmic consciousness,’ or revisit the trauma of your birth, you stand a good chance of having exactly that kind of experience.”
Celebrated author Aldous Huxley published The Doors of Perception in 1954, which told the story of his psychedelic experience. Pollan writes that readers of Huxley’s book reported having a similar “mystical” experience during their own session. These observations suggest that a psychedelic drug trip can perhaps be whatever you decide it will be.
The third phase is a critical follow-up review of the experience which seems to be correlated with those who experience a longer term therapeutic effect well beyond the trip itself.
With this managed level of control, interesting things have been happening. Matt Johnson, a researcher at John Hopkins, Pollan writes, “believes that psychedelics can be used to change all sorts of behaviors, not just addiction… In his view, the most important such model is the self, or ego, which a high-dose psychedelic experience temporarily dissolves.” “So much of human suffering,” Johnson said, “stems from having this self that needs to be psychologically defended at all costs. We’re trapped in a story that sees ourselves as independent, isolated agents in the world.”
While this ego protects us while “swinging through the trees or escaping from a cheetah, or trying to do your taxes,” it serves as a blocking mechanism that psychedelic drugs seem to disarm. “Psychedelics open a window of mental flexibility in which people can let go of the mental models we use to organize reality.” One stark anecdotal result is that terminally ill patients have reported losing their fear of death following psychedelic therapy. Other therapies include overcoming PTSD, anxiety, depression, addiction and more.
Psychedelic drug research raises other questions for Michael Pollan: “Why did [psilocybin mushrooms] evolve the ability to produce a chemical compound so closely related to serotonin, the neurotransmitter, that it can slip across the blood-brain barrier and temporarily take charge of the mammalian brain?”
Citing ethnobotanist and philosopher Terrence McKenna, who has developed a “stoned ape theory,” Pollan writes, “psilocybes gave our hominid ancestors ‘access to realms of supernatural power,’ ‘catalyzed the emergence of human self-reflection’ and ‘brought us out of the animal mind and into the world of articulated speech and imagination.’”
Referencing mycologist Paul Stamets, Pollan suggests that it was “‘more likely than not’ that psilocybin ‘was pivotal in human evolution’”
Pollan also ponders whether “the religious impulse in humankind had been first kindled by the visions inspired by a psychoactive mushroom.” This from ethnomycologist R. Gordon Wasson: “One is emboldened, to the point of asking whether [psychedelics] may not have planted in primitive man the very idea of God.” (Check here to see that this is not as crazy as it all sounds.*)
The church took notice of psychedelics long ago. Pollan writes that in 1620, “the Roman Catholic Church declared that the use of plants for divination was ‘an act of superstition condemned as opposed to the purity and integrity of our Holy Catholic Faith.’” That was over 400 years ago.
Pollan suggests that criticizing Timothy Leary for promoting LSD for all in the 1960s may have been premature. “It was one thing to use these drugs to treat the ill and maladjusted,” Pollan writes. “—Society will indulge any effort to help the wayward individual conform to its norms—but it is quite another to use them to treat society itself as if it were sick and turn the ostensibly healthy into wayward individuals.”
Those hippies may have been on to something after all.
*If all this sounds too much, remember that Pollan’s book was published in 2018. If you are interested in where this research has gone during nearly a decade of additional work, check out this September 2025 article published in the Journal of Personal Medicine.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12565330
You can also visit an updated comprehensive database of psychedelic research all over the world. Or, if you’re feeling adventurous, you can sign up as a guinea pig.
https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research
