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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.
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.
Lancet Psychiatry, 2016
Human Brain Mapping, 2015
Amanda Feilding (Coordinating Editor) and Nicola Singleton, with additional input from Alex Stevens, forthcoming
Human brain mapping, 2014
Journal of Psychopharmacology, 2014
Current Drug Abuse Reviews, 2014
Frontiers in human neuroscience, 2014
Current Drug Abuse Reviews, 2014
Journal of The Royal Society Interface, 2014
Frontiers in Human Neuroscience, 2014
Schizophrenia bulletin, 2013
The Journal of Neuroscience, 2013
The British Journal of Psychiatry, 2012
Proceedings of the National Academy of Sciences of the USA, 2012
Journal of Psychopharmacology, 2010
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