From the Independent Scientific Committee on Drugs media release,
23 January 2012
The findings of new research into the effects of psilocybin, the psychedelic drug chemical in magic mushrooms, are exciting scientists looking for therapies to treat psychiatric conditions.
Two new studies of this drug’s effect in humans are being published this week. Both contribute fresh knowledge to our understanding of psychedelic effects, which remain among the most mysterious human experiences.
The journal Proceedings of the National Academy of Sciences (PNAS) today publishes the results of a study which used two forms of brain scanning to investigate the effects of a moderate dose of psilocybin on 30 volunteers.
The subjective effects that the volunteers reported included dreamlike distortions of time, space and sensation, visions of geometric patterns, vivid flights of imagination and freely wandering thoughts. The scientists hoped to link these effects to observable changes in the brain.
The two fMRI techniques used measure blood flow and oxygenation. These factors are closely tied to brain activity, so measuring them amounts to an indirect measure of brain activity itself. Psychedelic drugs are popularly described as ‘mind-expanding’, but to the experimenters’ surprise, both forms of brain scan, BOLD fMRI and ASL fMRI, indicated only a reduction in brain activity.
The similarity of the results from the two techniques strongly support the validity of the conclusions, and further testing was carried out to demonstrate that changes observed in the blood oxygenation were due to changes in brain activity and not due to any direct effects of psilocybin on the brain’s blood supply.
When the volunteers were injected with psilocybin, the brain areas richest in connections to other areas quietened down. The posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC) are usually amongst the busiest parts of the brain, acting as information hubs, integrating sensory data into higher level thought. As Professor Nutt, the senior author of both papers explained, “this loss of connectivity might mean that consciousness is less constrained by inputs from the outside world via the senses, which could explain why people can imagine things very vividly”.
The team found that the more that activity in the mPFC was reduced by the drug, the more intense the volunteers found the psychedelic experience to be. This is persuasive evidence that the observed effects in the brain were indeed an explanation of subjective effects people feel. Whilst this by no means completes the scientific understanding of the psychedelic experience, for the first time, scientists were able to identify changes in the brain that underpin mental experiences that have been known about for thousands of years.
Previous studies on psilocybin have shown some very promising effects in combating depression, without the need for long-term medication. The suppression of the mPFC that the researchers observed provides an explanation of why. Depressed people have been shown to have greater levels of activity in the mPFC, which is believed to be linked to a tendency to brood persistently on fixed pessimistic thoughts. Upon recovery, the overactivity of the mPFC in depressed individuals has been seen to ebb. The researchers hypothesise that since psilocybin helps reduce mPFC activity, it could be used to break down entrenched negativity. Further research will be able to test these ideas.
The study to be published online later this week by the British Journal of Psychiatry investigated the effects of psilocybin on the recollection of emotionally significant memories. Dr Robin Carhart-Harris, a senior author of both studies, said “psilocybin was used extensively in psychotherapy in the 1950s, but the biological rationale for its use has not been properly investigated until now. Our findings support the idea that psilocybin facilitates access to personal memories and emotions.”
Fifteen volunteers were placed in an MRI scanner, then required to close their eyes and recollect specific personal memories which they had previously listed as having been happy, such as being at the altar getting married. Their brain activity was recorded, and they were also asked to rate aspects of their experience, such as how vivid the memories were. Each volunteer did this twice, once they were injected with psilocybin, and once they were injected with inactive saline (placebo).
The volunteers found that their memories whilst under the influence of psilocybin were significantly more visual and vivid. One participant said that the drug made him feel “more attached to the images and putting myself in the scenario”.
The fMRI imaging of their brains gave an insight into neurological processes behind their vivid recollections. When the participants were given psilocybin, brain regions involved with the senses were activated as they contemplated memories. The memories had a deeper sense of realism as their imaginations seemed to be creating a window into the sights and sounds of their pasts.
Dr Robin Carhart-Harris said “This effect needs to be investigated further but it suggests that used in combination with psychotherapy, psilocybin might help people recall positive life events and reverse pessimistic mindsets.
Psilocybin is a Class A drug under the UK’s Misuse of Drugs Act. According to the hovernment, “Class A drugs are considered to be the most likely to cause harm”, and so possession of them carries the highest penalties; up to seven years in prison and an unlimited fine. The classification of psilocybin under UK law follow the United Nations Convention on Psychotropic Substances, which in 1973 designated psilocybin as Schedule 1, the category with the most stringent controls. However, the law makes a particular exception for research. Professor Nutt holds a rare Home Office licence for the storage and handling of drugs in studies such as these. The risks of administering psilocybin were carefully managed, including by recruiting only volunteers with previous positive experience of psychedelics, and the studies were approved by NHS research ethics committees.
The Schedule 1 classification, which psilocybin received back in 1973, is reserved for drugs which, when listed, were considered not only immensely dangerous, but also of no therapeutic value. Schedule 1 status raises numerous obstacles for research, and in the last four decades these new studies are among the only projects on psilocybin in human subjects that have been able to proceed. The new evidence that has been collected brings into question whether the stringent regulation of Schedule 1 drugs really does serve the interests of public health. More research is urgently needed to fully evaluate the safety and effectiveness of psilocybin as a therapeutic tool, but with so few scientists licensed to carry out this work, this will be a slow process. If psilocybin could indeed be used to relieve the suffering of people with psychiatric disorders, it is unfortunate that sufferers will not have access to this in the coming years.
The research is the product of collaboration of a diverse group of people from across several disciplines and institutions, including the Neuropsychopharmacology Unit at Imperial College London, the Unit of Psychiatry at the University of Bristol, and Cardiff University’s Brain Research Imaging Centre. Professor David Nutt, the Chair of the Independent Scientific Committee on Drugs, was the senior author of both studies. The study in PNAS was edited by Professor Les Iversen of Oxford University, the Chair of the Government’s Advisory Council on the Misuse of Drugs. It was funded by the Beckley Foundation, the Multidisciplinary Association for Psychedelic Studies, and the Heffner Research Institute, all bodies which support the scientific investigation of consciousness and the use of psychedelics to alleviate suffering.
AND ANOTHER NEWS STORY ON THIS STUDY:
fMRI brain imaging illuminates magic mushrooms' psychedelic effects
Imperial College London, via Medical Express
23 January 2012
Brain scans of people under the influence of the psilocybin, the active ingredient in magic mushrooms, have given scientists the most detailed picture to date of how psychedelic drugs work. The findings of two studies being published in scientific journals this week identify areas of the brain where activity is suppressed by psilocybin and suggest that it helps people to experience memories more vividly.
In the first study, published today in Proceedings of the National Academy of Sciences (PNAS), 30 healthy volunteers had psilocybin infused into their blood while inside magnetic resonance imaging (MRI) scanners, which measure changes in brain activity. The scans showed that activity decreased in "hub" regions of the brain – areas that are especially well-connected with other areas.
The second study, due to be published online by the British Journal of Psychiatry on Thursday, found that psilocybin enhanced volunteers' recollections of personal memories, which the researchers suggest could make it useful as an adjunct to psychotherapy.
Professor David Nutt, from the Department of Medicine at Imperial College London, the senior author of both studies, said: "Psychedelics are thought of as 'mind-expanding' drugs so it has commonly been assumed that they work by increasing brain activity, but surprisingly, we found that psilocybin actually caused activity to decrease in areas that have the densest connections with other areas. These hubs constrain our experience of the world and keep it orderly. We now know that deactivating these regions leads to a state in which the world is experienced as strange."
The intensity of the effects reported by the participants, including visions of geometric patterns, unusual bodily sensations and altered sense of space and time, correlated with a decrease in oxygenation and blood flow in certain parts of the brain.
The function of these areas, the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC), is the subject of debate among neuroscientists, but the PCC is proposed to have a role in consciousness and self-identity. The mPFC is known to be hyperactive in depression, so psilocybin's action on this area could be responsible for some antidepressant effects that have been reported. Similarly, psilocybin reduced blood flow in the hypothalamus, where blood flow is increased during cluster headaches, perhaps explaining why some sufferers have said symptoms improved under psilocybin.
In the British Journal of Psychiatry study 10 volunteers viewed written cues that prompted them to think about memories associated with strong positive emotions while inside the brain scanner. The participants rated their recollections as being more vivid after taking psilocybin compared with a placebo, and with psilocybin there was increased activity in areas of the brain that process vision and other sensory information.
Participants were also asked to rate changes in their emotional wellbeing two weeks after taking the psilocybin and placebo. Their ratings of memory vividness under the drug showed a significant positive correlation with their wellbeing two weeks afterwards. In a previous study of 12 people in 2011, researchers found that people with anxiety who were given a single psilocybin treatment had decreased depression scores six months later.
Dr Robin Carhart-Harris, from the Department of Medicine at Imperial College London, the first author of both papers, said: "Psilocybin was used extensively in psychotherapy in the 1950s, but the biological rationale for its use has not been properly investigated until now. Our findings support the idea that psilocybin facilitates access to personal memories and emotions.
"Previous studies have suggested that psilocybin can improve people's sense of emotional wellbeing and even reduce depression in people with anxiety. This is consistent with our finding that psilocybin decreases mPFC activity, as many effective depression treatments do. The effects need to be investigated further, and ours was only a small study, but we are interested in exploring psilocybin's potential as a therapeutic tool."
The researchers acknowledged that because the participants in this study had volunteered after having previous experience of psychedelics, they may have held prior assumptions about the drugs which could have contributed to the positive memory rating and the reports of improved wellbeing in the follow-up.
Functional MRI measures brain activity indirectly by mapping blood flow or the oxygen levels in the blood. When an area becomes more active, it uses more glucose, but generates energy in rapid chemical reactions that do not use oxygen. Consequently, blood flow increases but oxygen consumption does not, resulting in a higher concentration of oxygen in blood in the local veins.
In the PNAS study, the volunteers were split into two groups, each studied using a different type of fMRI: 15 were scanned using arterial spin labelling (ASL) perfusion fMRI, which measures blood flow, and 15 using blood-oxygen level-dependent (BOLD) fMRI. The two modalities produced similar results, strongly suggesting that the observed effects were genuine.
More information: R Carhart-Harris et al. 'Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.' Proceedings of the National Academy of Sciences, published online 23 January 2012.
R Carhart-Harris et al. 'Implications for psychedelic-assisted psychotherapy: a functional magnetic resonance imaging study.' British Journal of Psychiatry, published online 26 January 2012.
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