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The Science

Imperial College Psilocybin Research: What the Studies Have Found

A summary of the most influential research center in modern psychedelic science — the Imperial College London team that produced the first fMRI study of psilocybin and the first head-to-head trial against an SSRI.

By The Microdose Movement ·

In one sentence: The Imperial College London Centre for Psychedelic Research has produced more of the foundational science behind modern psilocybin medicine than any other institution in the world.

If you have read about psilocybin’s effect on the brain, the Default Mode Network, psilocybin for depression, or the comparison of psychedelics to antidepressants, you have probably read findings from Imperial College London — even if the institution was not named in the article you read. For more than a decade, the team at Imperial has been responsible for many of the studies that shifted psilocybin from a Schedule I curiosity into a serious area of clinical research.

This page is a summary of who they are, what they have published, and why their work matters.

Who is the Imperial College psilocybin team?

The work began in the late 2000s under the leadership of Professor David Nutt, a neuropsychopharmacologist and former chief drug advisor to the UK government. Nutt had become publicly known for arguing that drug policy should be guided by actual harm data rather than political tradition — a stance that cost him his government position in 2009 but freed him to pursue research that more cautious institutions were avoiding.

Around the same time, a young researcher named Robin Carhart-Harris joined Nutt’s lab. Carhart-Harris had been interested in psychedelics since reading about Stanislav Grof’s work as a teenager and had studied psychoanalytic theory at Brunel University before moving into neuroscience. Together, Nutt and Carhart-Harris assembled the team that would become the Centre for Psychedelic Research, formally founded at Imperial in April 2019. It was the world’s first dedicated academic center for psychedelic research at a major university.

Carhart-Harris led the centre as its founding director until 2021, when he moved to the University of California, San Francisco. The Imperial centre continues under new leadership, and Carhart-Harris’s work continues to shape the field from California.

The 2012 fMRI study: how psilocybin affects the brain

The team’s first major contribution was published in PNAS in January 2012 under the title “Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.” It was the first formal fMRI study to image the brain under the influence of psilocybin in humans.

The findings were unexpected. Most researchers had assumed psychedelics would increase activity across the brain — more stimulation, more processing, more activity. The Imperial team found the opposite. Psilocybin decreased blood flow and oxygenation in the brain’s hub regions, particularly the medial prefrontal cortex and posterior cingulate cortex — the core nodes of the Default Mode Network.

The team also found that the synchronized activity between DMN regions, which normally fire together as a coordinated unit, became less synchronized. The brain’s “self” network was loosening its grip on the rest of the system.

This study reframed how researchers think about what psychedelics do mechanistically. The story was no longer “drugs that flood the brain with stimulation.” It became “drugs that reduce the constraints the brain normally imposes on its own activity.” This reframing has guided most psilocybin research since.

The 2014 entropic brain hypothesis

Two years later, Carhart-Harris and colleagues published a theoretical paper in Frontiers in Human Neuroscience called “The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.” The paper introduced the entropic brain hypothesis — the idea that consciousness can be characterized by the entropy of brain activity, and that psychedelics increase that entropy.

In plain language: under normal conditions, the brain operates in a relatively constrained, low-entropy state. Predictable patterns dominate. The same regions talk to the same regions in the same ways. Psychedelics temporarily increase the variety of brain states, allowing patterns the brain normally suppresses to emerge.

The hypothesis became the theoretical scaffolding for much of the subsequent psychedelic research. It provided a framework for understanding why a single intense psychedelic experience might produce lasting psychological change: by temporarily shaking the brain out of its dominant patterns, the experience makes new patterns possible.

The 2016 open-label depression study

In 2016, the Imperial team published the first modern study of psilocybin for treatment-resistant depression. Twelve patients with depression that had failed multiple conventional treatments received two psilocybin sessions. The study was open-label and uncontrolled, meaning everyone knew they were getting the drug and there was no placebo group. Methodologically modest by clinical trial standards.

The results, published in The Lancet Psychiatry, were nonetheless striking. All twelve patients showed reduced depressive symptoms one week after the sessions. Eight of them showed clinically significant improvement at three months. Five of them remained in response or remission six months later. None of these patients had responded meaningfully to standard treatments before.

The study was the proof of concept that justified the larger, more rigorous trials that followed. It also brought significant public attention to the question of whether psilocybin might be a serious treatment for depression and not just a research curiosity.

The 2021 head-to-head trial against escitalopram

The most consequential single study from the Imperial team was published in the New England Journal of Medicine in April 2021. Carhart-Harris and colleagues conducted a six-week double-blind, randomized trial comparing psilocybin to escitalopram (Lexapro) in 59 patients with moderate-to-severe major depression.

The design was unusually rigorous for psychedelic research. Half the patients received two doses of psilocybin (25mg) plus daily placebo capsules. The other half received daily escitalopram plus two psilocybin-shaped placebo doses. Neither patients nor evaluators knew which group anyone was in.

The findings:

The study did not prove psilocybin is better than escitalopram on the primary measure. It did show that psilocybin is at least competitive with one of the most-prescribed antidepressants in the world, with a different side effect profile and a different time course. For a Schedule I substance compared to a billion-dollar pharmaceutical, that is a remarkable result.

This study is the closest thing the field has to a phase II clinical trial of psilocybin as a depression treatment, and it accelerated regulatory and commercial interest in psychedelic medicine more than any other single paper.

Other notable Imperial publications

The team has produced dozens of papers across the past decade. A short list of the most cited:

The full publication list of the Centre for Psychedelic Research is maintained on its Imperial website.

Why the Imperial work matters for microdosing

The Imperial team’s research has been done almost entirely with full doses of psilocybin in clinical settings, not microdoses. This is an important caveat. The dramatic findings on the Default Mode Network, neuroplasticity, and depression treatment are based on guided sessions with 20-25mg doses, not the 0.1-0.2g of dried mushrooms a microdoser would take.

Microdoses likely produce qualitatively similar effects at much smaller magnitudes. Whether they produce the same kind of clinical benefit is an active research question that the Imperial team and other groups are still working on.

What the Imperial work does provide for microdosers is the foundational mechanistic understanding: this is what psilocybin does to the brain, this is the receptor pathway, this is the network effect, this is the relationship to depression and emotional life. The microdosing practice rests on this scientific scaffolding even when the dose itself is much smaller.

Frequently Asked Questions

What is the Centre for Psychedelic Research at Imperial College London?

The Centre for Psychedelic Research is the world’s first dedicated academic research center for psychedelic studies at a major university. It was founded at Imperial College London in April 2019 under the leadership of Robin Carhart-Harris and David Nutt.

Who is Robin Carhart-Harris?

Robin Carhart-Harris is a British neuroscientist who led much of the early modern psilocybin research at Imperial College London. He founded the Centre for Psychedelic Research in 2019 and moved to the University of California, San Francisco in 2021.

What did the 2021 Imperial study compare?

The 2021 study compared psilocybin to escitalopram (Lexapro) in patients with moderate-to-severe major depression. Psilocybin matched escitalopram on the primary outcome and outperformed it on several secondary outcomes including well-being and side effect profile.

Has Imperial College studied microdosing specifically?

Most of the Imperial team’s research has used full doses in clinical settings rather than microdoses. The 2021 Szigeti microdosing study at Imperial — which found microdose effects were largely explained by placebo — is the most relevant Imperial work on microdosing specifically.

No. Psilocybin remains a Schedule 1 controlled substance in the UK. The Imperial research has been conducted under special research licenses. Clinical use is not currently approved, though research and policy discussion is active.

Sources and Further Reading

This page is for educational purposes. Nothing here is medical advice. The Microdose Movement is an educational community, not a clinical provider.