Research & Culture7 min read

The New Science of Psilocybin: Johns Hopkins, NYU, Imperial and COMPASS Explained

Headlines about psilocybin swing between "miracle cure" and "dangerous drug". The real research is more interesting than either. Over the past two decades, a handful of carefully designed studies at Johns Hopkins University, New York University, Imperial College London and elsewhere have reshaped how scientists think about this compound. This guide walks through the landmark studies in plain language, what they actually found, and the limits that every honest reader should keep in mind.

A quick note before we start: none of this means psilocybin is an approved treatment in Canada, and nothing here is medical advice. Clinical trials use pure, precisely measured synthetic psilocybin, careful screening, and trained therapists in a controlled setting. That is very different from taking mushrooms at home.

Some background: the first wave and the long pause

Scientists first studied psilocybin in the late 1950s and 1960s, soon after Swiss chemist Albert Hofmann isolated it (we tell that story in our history post). Early research was enthusiastic but often loosely designed. As psychedelics became tied to the counterculture, governments tightened control, and by the early 1970s psilocybin was placed in the most restrictive international category under the 1971 United Nations Convention on Psychotropic Substances. Human research almost stopped for about thirty years.

Johns Hopkins, 2006: the mystical experience study

The study that restarted serious interest came from Roland Griffiths and colleagues at Johns Hopkins, published in the journal Psychopharmacology in 2006.

Who took part: 36 healthy adults who had never used hallucinogens and who reported regular spiritual or religious activity.
What they got: a high dose of psilocybin (30 mg per 70 kg of body weight) in one session, and methylphenidate (a stimulant, used as an active placebo) in another, in a double-blind design so neither participants nor monitors knew which was which.
The setting: a comfortable living-room-style space, eyeshades, headphones with music, and two trained monitors present throughout.

The results were striking. Psilocybin produced much higher scores on questionnaires measuring mystical-type experience, such as a sense of unity, sacredness and deep positive mood. Two months later, participants rated the psilocybin session as having substantial personal meaning and spiritual significance, and people close to them reported positive changes in their attitudes and behaviour.

The study also recorded the downsides honestly: some participants experienced significant fear or anxiety during the session, even in that carefully controlled setting. That finding is one reason the same team later published detailed safety guidelines for human research.

In December 2016, the Journal of Psychopharmacology published two randomized, double-blind trials side by side, both looking at people with life-threatening cancer who were struggling with depression and anxiety.

At Johns Hopkins, Griffiths and colleagues studied 51 patients in a crossover trial comparing a very low dose with a high dose of psilocybin. The high dose produced large decreases in depressed mood and anxiety, along with improvements in quality of life, sense of meaning and optimism, and reduced anxiety about death. At the six-month follow-up, about 80 per cent of participants still showed clinically significant reductions in depressed mood and anxiety.

At NYU, Stephen Ross and colleagues studied 29 patients who received a single moderate dose of psilocybin (0.3 mg per kg) or niacin as a comparison, along with psychotherapy, before crossing over. Psilocybin led to rapid and sustained improvements in anxiety and depression, and at a follow-up of about six and a half months, roughly 60 to 80 per cent of participants continued to show clinically significant reductions.

In both studies, the intensity of the mystical-type experience during the session was linked to how much people improved. That's a recurring theme in psilocybin research: the content of the experience seems to matter, not just the chemistry.

Imperial College London: depression

Robin Carhart-Harris, David Nutt and colleagues at Imperial College London led much of the depression research.

In 2016, they published a small open-label feasibility study in The Lancet Psychiatry. People with treatment-resistant depression received two doses of psilocybin, 10 mg and then 25 mg, with psychological support. Depression scores dropped markedly in the weeks afterward. Because there was no control group and everyone knew what they were taking, it couldn't prove psilocybin caused the improvement, but it justified larger trials.

In 2021, the same group published a double-blind trial in the New England Journal of Medicine comparing psilocybin with escitalopram, a common SSRI antidepressant, in 59 people with moderate to severe depression over six weeks. On the main measure, the difference between the two groups was not statistically significant. Several secondary measures leaned in psilocybin's favour, including higher response and remission rates, but the authors cautioned that these needed confirmation in bigger, longer studies. It was an important, honest result: promising, not conclusive.

Imperial's brain-imaging work also gave us one of the most quoted ideas in the field: that psilocybin temporarily loosens the brain's usual patterns of communication, especially in networks linked to self-focused thinking, and increases communication between regions that don't normally talk much. This is still an active area of research, and the details are debated.

COMPASS Pathways, 2022: the largest trial yet

In November 2022, the New England Journal of Medicine published a phase 2b trial of COMP360, a synthetic psilocybin formulation developed by COMPASS Pathways, led by Guy Goodwin and colleagues.

Who took part: 233 people with treatment-resistant depression across several countries.
What they got: a single dose of 25 mg, 10 mg or 1 mg (the 1 mg group served as a near-placebo control), with psychological support before, during and after.
What happened: at three weeks, the 25 mg group showed a significantly greater reduction in depression scores than the 1 mg group. The 10 mg dose did not differ significantly from 1 mg. By 12 weeks, the difference was smaller and less clear.

The trial also reported adverse events carefully. Headache, nausea and dizziness were common. More worryingly, suicidal ideation and self-injury were reported in all three groups, including in the 25 mg group. Researchers emphasized the need for close monitoring and further study. This is exactly the kind of nuance that headlines tend to skip.

What the research does and doesn't tell us

The honest summary is that psilocybin, given in a carefully prepared clinical setting with professional support, has shown real promise in early trials for depression and for distress related to serious illness. But:

Most trials are small and short. Long-term data are still limited.
Blinding is hard. People usually know whether they got a strong psychedelic, which can inflate the effects.
Participants are heavily screened. People with psychosis risk, bipolar disorder, heart problems and many medications are usually excluded.
The therapy matters. Results come from psilocybin plus preparation, support and integration, not a pill on its own.
Effects can fade. Some benefits diminish over weeks or months.

None of it shows that taking mushrooms at home treats any condition. If you are dealing with depression or anxiety, please talk to a doctor or mental health professional.

What clinical sessions can teach home users

Even though home use is not therapy, the way trials run sessions holds some wisdom:

Preparation before the session, including talking through fears and intentions.
A safe, comfortable, private room.
Eyeshades and a thoughtful playlist.
A calm, sober person present the whole time.
Time afterwards to reflect and make sense of the experience.

Our set and setting guide, trip sitting guide and integration guide borrow these principles for everyday life.

How clinical doses compare to mushrooms

The high doses used in trials, around 25 mg of pure psilocybin, are roughly comparable to a strong mushroom dose of a few grams of dried Psilocybe cubensis. That is an approximation only: the psilocybin content of mushrooms varies a lot by strain, growing conditions and batch, which is one reason trials use synthetic psilocybin. For mushrooms, think in these approximate bands: microdose about 0.05 to 0.25 g, low about 0.5 to 1 g, moderate about 1 to 2.5 g, strong about 2.5 to 3.5 g. Our dose sizes guide explains more.

Safety and the law

Psilocybin is a controlled substance in Canada. Limited legal access exists through Health Canada's Special Access Program and exemptions, covered in our Canada post. Avoid psilocybin if you have a personal or family history of psychosis or bipolar disorder, a heart condition, or take lithium, MAOIs, tramadol or antidepressants without medical advice. You must be 19 or older to shop with us. Never drive after taking mushrooms.

Sources

This guide is general information, not medical or legal advice. If you have health questions, talk to a health professional.