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Our research with Psilocybin

Psilocybin is the psychoactive compound from hallucinogenic mushrooms, commonly called psilocybin or magic mushrooms. Exactly how psilocybin produces its characteristic mind-altering effects is unknown. However, our work with Prof David Nutt and Dr Robin Carhart-Harris in the Beckley / Imperial Research Programme is beginning to shed light on these mechanisms for the first time.

Using the most advanced brain imaging techniques (arterial spin labelling, functional MRI, and MEG) to measure brain blood flow, functional connectivity, and ‘brain waves,’ the Programme examines changes in the brain brought on by psilocybin, adding to the evidence base supporting its therapeutic potential, while teaching us about consciousness itself.

Our imaging data indicate that psychedelics (both LSD and psilocybin) produce a disorganised, or ‘entropic,’ brain state and a more disordered and fluid state of consciousness. This has important therapeutic implications, as certain mental health conditions can be conceptualised as ‘inflexible’ and ‘excessively organised’ patterns of thought, and psychedelics may break down these patterns by dismantling the brain activity patterns on which they rest.

In addition to investigating the effects of psilocybin on the brain, we are also examining its potential clinical benefits. Based on our brain imaging results, in 2012, the Medical Research Council awarded funding to the Beckley/Imperial Research Programme for a clinical study investigating psilocybin in the treatment of depression. Results from the study, published in the Lancet Psychiatry Journal, showed that two doses of psilocybin lifted depression in all 12 volunteers for three weeks, and kept five of them depression free for three months.

The size of the study and the absence of a placebo make the research proof of principle only, but the remarkably positive results highlight the need for continued research in this promising area of psychiatry – psychedelic-assisted therapy. We are currently trying to secure funding to expand this research and further evaluate the potential of psilocybin as a treatment for depression.

We were also involved in the pioneering pilot trial led by Prof Roland Griffiths and Dr Matt Johnson at Johns Hopkins University, which was the first study in modern times to investigate the efficacy of psilocybin as an aid to smoking cessation. The results were extremely promising, with 80% of participants still abstinent at 6-month follow-up – an unprecedented success rate. A second, larger trial with a brain imaging component is now underway.

About Psilocybin

Mushrooms containing the psychoactive compounds psilocybin and psilocin (also called ‘magic mushrooms’) are found naturally occurring all over the world; England, Mexico, Hawaii, and Thailand all have indigenous strains. Psilocybin mushrooms have been used since prehistoric times, with the earliest archaeological accounts dating back to 7000BC.

Psilocybin mushrooms were known to the Aztecs as teonanácatl (meaning ‘divine mushroom’) and have played an important role in Aztec and other indigenous groups’ cultural and religious traditions. Their ceremonial use remains important today, especially among the Mazatecs and Zapotecs in Oaxaca, southern Mexico.

There are over one hundred and eighty species of mushrooms around the world that contain the psychoactive  compounds, psilocybin or psilocin. Despite their widespread natural occurrence, psilocybin mushrooms were made illegal internationally by the 1971 UN Single Convention on Psychotropic Drugs.

The mushrooms’ psychoactive compounds, psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine or 4-PO-DMT)  and psilocin, were isolated in 1958 by Albert Hofmann. Psilocybin is chemically related to another compound, tryptophan, from which the brain chemicals serotonin and melatonin are derived. Psilocybin is rapidly converted in the body to the more potent compound psilocin, which interacts with the serotonin system. Serotonin (abbreviated 5-HT for 5-hydroxytryptamine) is a naturally occurring brain chemical (‘neurotransmitter’) that binds to serotonin receptors. Numerous serotonin receptor subtypes have been discovered and are identified by number-letter combinations. Psilocybin primarily binds to serotonin 2A (5-HT2A) receptors. However, it causes a different series of events to happen than serotonin does, which is why psilocybin has psychedelic effects and serotonin does not.

Read more about our psilocybin research in the media

“A good way to understand how the brain works is to perturb the system in a marked and novel way. Psychedelic drugs do precisely this and so are powerful tools for exploring what happens in the brain when consciousness is profoundly altered. It is the first time we have used these methods to look at brain imaging data and it has given some fascinating insight into how psychedelic drugs expand the mind. It really provides a window through which to study the doors of perception”.
Enzo Tagliazucchi about the Beckley/Imperial psilocybin research


Long-term follow-up of psilocybin-facilitated smoking cessation

The American Journal of Drug and Alcohol Abuse, 2016

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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Lancet Psychiatry, 2016

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Finding the self by losing the self: Neural correlates of ego dissolution under psilocybin

Human Brain Mapping, 2015

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Roadmaps to Regulation: Cannabis, Psychedelics, MDMA, and NPS

Amanda Feilding (Coordinating Editor) and Nicola Singleton, with additional input from Alex Stevens, forthcoming

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Enhanced repertoire of brain dynamical states during the psychedelic experience

Human brain mapping, 2014

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Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

Journal of Psychopharmacology, 2014

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Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction

Current Drug Abuse Reviews, 2014

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The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Frontiers in human neuroscience, 2014

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A qualitative report on the subjective experience of intravenous psilocybin administered in an FMRI environment

Current Drug Abuse Reviews, 2014

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Homological scaffolds of brain functional networks

Journal of The Royal Society Interface, 2014

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The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

Frontiers in Human Neuroscience, 2014

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Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis

Schizophrenia bulletin, 2013

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Cannabis and the Psychedelics: Reviewing the UN Drug Conventions

Prohibition, Religious Freedom, and Human Rights: Regulating Traditional Drug Use, 2013

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Broadband cortical desynchronization underlies the human psychedelic state

The Journal of Neuroscience, 2013

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Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin

The British Journal of Psychiatry, 2012

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Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

 Proceedings of the National Academy of Sciences of the USA, 2012

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The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

 Journal of Psychopharmacology, 2010

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