Raku ga ku su

Psilocybin names the principal psychoactive compound in psilocybin mushrooms and, in common usage, the class of mushrooms that contain it. In the book it occupies two registers at once: a substance whose action can be investigated at a receptor, and a means of entering experiences whose personal meaning cannot be reduced to that chemistry. Its role in the narrator’s journey and in clinical trials makes it a central point of contact between subjective experience, scientific measurement, and the return of psychedelic therapy to medical research.

Compound and mechanism

Psilocybin belongs to the tryptamine group known as the classical psychedelics. The compounds in this group resemble serotonin sufficiently to bind to and activate the 5-HT2A receptor, which is abundant in the human cortex. That biochemical account gives researchers a point of entry into the drug’s action, but not a complete explanation of the experience it produces. The distinction matters throughout the book: identifying a receptor does not explain how a person’s sense of self changes, why subject and object may seem to lose their separation, or why an experience takes one particular emotional and perceptual shape.

The science linking serotonin and LSD had contributed to the development of neurochemistry from the 1950s onward, but the specific evidence for the receptor mechanism came later. In 1998, Franz Vollenweider gave participants ketanserin, which blocks the 5-HT2A receptor, and then administered psilocybin. When the receptor was blocked, the expected effects did not occur. The finding established an important part of the pharmacological pathway: psilocybin’s effects depend on the receptor. It did not, by itself, bridge the gap from a molecular interaction to the contents of consciousness.

Personal experience and the limits of measurement

That gap becomes especially clear in the narrator’s contrasting experiences with psilocybin and a toad-derived psychedelic. The same Mystical Experience Questionnaire that seemed to fit the latter experience poorly felt more apt when applied to the psilocybin journey with Judith. Reflecting on a cello interlude, the narrator could readily endorse descriptions of personal self merging into a larger whole, sacredness, spiritual elevation, and unity with ultimate reality. Those endorsements described the experience’s character without requiring belief in a supernatural reality.

The psilocybin journey received a score of sixty-six on the questionnaire, and the narrator felt a measure of pride in having reached a result that scientists would classify as a mystical experience. Yet the score did not bring a belief in God, cosmic consciousness, or magic. The experience seemed novel and profound, and the narrator was willing to call it spiritual, but only with reservations about whether spirituality necessarily entails religious faith. The tension is important: a questionnaire can classify reported features, but the resulting category does not dictate what a participant believes those features mean.

The book connects that tension to the case of Dinah Bazer, a cancer patient at New York University who remained an avowed atheist before and after her psilocybin session. At the height of the experience, she described being immersed in divine love, yet she did not abandon her atheism. The account suggests that religious language can express the scale and unearned quality of an overwhelming experience without functioning as a literal statement of religious belief. In this way, psilocybin’s effects complicate any simple division between spiritual experience and secular identity.

Clinical design and cancer research

The New York University cancer trial placed the drug in a carefully structured therapeutic setting. Patrick Mettes first completed three or four preparatory therapy sessions, then took part in two dosing sessions: one with a high dose of niacin, used as an active placebo because it produces a tingling sensation, and one with twenty-five milligrams of psilocybin. Each session occupied most of a day. Mettes lay on a couch wearing eyeshades and listening to a curated playlist that included Brian Eno, Philip Glass, Pat Metheny, Ravi Shankar, and classical and New Age music. Tony Bossis and Krystallia Kalliontzi sat with him, available to help but instructed to say little. The protocol thus treated the drug as part of a therapeutic encounter shaped by preparation, music, supervision, and expectation, rather than as an isolated chemical intervention.

The New York University study and a parallel study at Johns Hopkins University tested whether a single high dose could relieve the anxiety and depression that can follow a life-threatening cancer diagnosis. Their results, published together in a special issue of the Journal of Psychopharmacology and reported in a front-page New York Times story in December 2016, attracted prominent support from the mental health establishment. In both trials, about 80 percent of participants showed clinically significant reductions in anxiety and depression, with effects lasting at least six months. Across the studies, the intensity of participants’ reported mystical experiences closely correlated with the degree of symptom relief.

The combined trials involved only eighty subjects, so their results required replication at a larger scale before they could support regulatory changes. Even so, the findings helped shift psilocybin research from the margins toward cautious medical acceptance. Medical schools sought to participate in further trials, funders offered support, and New York University expanded its institutional commitment: it invited Stephen Ross to move his treatment room from the dental college into the main hospital, while the cancer center asked him to establish a room there for a subsequent trial. The changes marked a practical consequence of the research, not merely a change in public reputation.

Research beyond cancer

Psilocybin research also extended to addiction. At Johns Hopkins University, Matthew Johnson’s open-label smoking-cessation pilot combined several sessions of cognitive behavioral therapy with two or three psilocybin doses for fifteen volunteers trying to quit. Participants knew they were receiving the drug; there was no placebo group. They had to stop smoking before the session, and researchers measured carbon-monoxide levels at intervals to check abstinence. Six months after treatment, 80 percent were confirmed abstinent; at one year, 67 percent remained so. The study was small and not randomized, but its results were striking for an addiction considered especially difficult to break. The participants reporting the most complete mystical experiences had the best outcomes. A larger randomized comparison with the nicotine patch was under way.

A depression study led by Robin Carhart-Harris in David Nutt’s laboratory at Imperial College London tested psilocybin in people with treatment-resistant depression, defined as depression that had not responded to at least two previous treatments. The initial feasibility study enrolled twelve participants, six men and six women, without a control group. After a week, all showed symptom improvement, and two-thirds were depression-free; seven still had substantial benefit after three months. The expanded study included twenty people. At six months, six remained in remission, while others had relapsed to varying degrees, suggesting that treatment might need to be repeated. The study was modest and uncontrolled, but reported rapid, marked benefits and no adverse events. The European Medicines Agency considered the data encouraging enough to propose a larger trial, in a region where treatment-resistant depression affected more than 800,000 people.

Revival and unresolved questions

The clinical studies were part of a wider revival after psychedelic research had been halted under cultural and political pressure. Researchers at New York University and Johns Hopkins were, in effect, resuming questions explored by earlier generations, while seeking to repeat the work under contemporary scientific standards. The Heffter Research Institute, founded in 1993 when psychedelic research had been dormant for two decades, helped fund most American psilocybin trials since the late 1990s, including the work at those two universities. Its quiet financial support connected the revival’s institutional infrastructure to the clinical findings.

The research also exposed difficulties built into the experimental method. Participants and guides can often tell whether psilocybin or a placebo has been administered, making conventional blinding difficult. Researchers must also contend with Set and setting: the context, therapeutic relationship, and expectations that may shape the experience alongside the drug’s chemistry. A study designed to isolate one variable therefore confronts a treatment whose effects may depend on several interacting conditions. Psilocybin’s significance in the book lies partly in this unresolved challenge. Its receptor action is experimentally tractable; its subjective effects, therapeutic context, and meanings remain more difficult to separate, measure, and explain.