Magic Mushroom Mechanism Revealed

Originally appearing here. “Magic mushrooms could one day be prescribed for depression,” The Independent has today reported. The newspaper said the approach is based on potentially using its chemical properties to trigger positive memories during psychotherapy. A number of newspapers have reported similar news, which is based on research led by the former government drugs adviser Professor David Nutt. For example, the Daily Mirror reported that the use of psilocybin, the active ingredient in magic mushrooms, is being considered as part of therapy for depression. These claims are based on a pair of research studies, one published today and another to be published in the near future. The study published today looked at brain activity in 30 people using a special type of MRI scan to help establish how psilocybin causes sensations such as hallucinations. The research compared the brain’s workings when given psilocybin and a placebo. It found that the psychoactive compound decreased activity in various brain areas and that greater decreases were linked to more intense experiences. Crucially, this exploratory study was not a clinical trial or an examination of the effect psilocybin has on people with depression. Therefore, it is not possible to say from this research whether psilocybin could have benefits for people with depression. Also, importantly, the possible harms of using this drug, either in the short or long term have not been studied here. Where did the story come from? The study was carried out by researchers from Imperial College London and the University of Bristol. It was funded by a range of research and policy foundations: The Beckley Foundation, The Neuropsychoanalysis Foundation, Multidisciplinary Association for Psychedelic Studies, and The Heffter Foundation. The study was published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences (PNAS). The headlines featured in The Daily Telegraph and The Independent suggested that magic mushrooms are being considered as a treatment for depression. The study itself looked at how the brain was affected by a hallucinogenic chemical in the mushrooms, rather than using them in a medicinal manner. As this study did not look at whether psilocybin had any beneficial effects for depression, it will take further study to see whether it does have any beneficial effect and if it is safe. It has been reported that a related trial looking at the psychological impact of psilocybin is to be published in the near future, although Behind the Headlines cannot verify the nature of this research and its findings until the research paper is available. Metro had correctly reported the current research’s finding that psilocybin reduces blood flow. However, its headline suggesting the drug ‘narrows the mind’ is misleading and confusing. What kind of research was this? This brain imaging study used a special type of MRI scan called functional MRI (fMRI) that measures brain activity by detecting changes in blood flow. Researchers used this to look at how a psychedelic chemical found in magic mushrooms affected the brain activity of 30 healthy volunteers who did not have depression. The researchers said that although the hallucinogenic chemical has been reported to cause ‘profound existential experiences’ that can leave a long-lasting impression, little is known about how psilocybin actually affects the brain. The volunteers in this study had experienced hallucinogens before and did not have depression. Therefore, it is not possible to say whether these people would have exactly the same experience as people who had current or past depression, or people who had never experienced the sensation of hallucinating. This was not a clinical trial and did not look at the effects of the drug on depression. What did the research involve? The study recruited five women and 10 men who had previously used a hallucinogenic drug and had no history of any psychiatric disorder, substance dependence or cardiovascular disease. The volunteers had an average age of 34 years. The volunteers first had a normal MRI scan taken to look at the structure of their brain. They then had functional MRI scans to look at blood flow within their brains while they received an infusion of either a placebo, in the first scan, or psilocybin in the second scan. These infusions were administered six minutes after the scan began, and took 60 seconds to be delivered. The functional scans took 18 minutes and during this time the volunteers were asked to relax and stare at a cross. Before the infusion, five minutes after, and 12 minutes after, the volunteers were asked to rate their feelings from 0-10, where a score of 10 represented ‘extremely intense effects’. After each scan the volunteers were asked to rate how much they experienced 19 different aspects of hallucination. These subjective effects included, for example, seeing geometric patterns, feeling that their sense of time was altered, and feeling unusual body sensations. The researchers looked at the pattern of blood flow (a marker of brain activity) before and after the infusions. The researchers additionally performed functional brain scans on a further 15 volunteers, using a slightly different type of functional MRI scan that measures the amount of oxygen in the blood going to and from the brain as a measure of brain activity. What were the basic results? The researchers found that the volunteers’ subjective experiences started towards the beginning of the infusion period and peaked after four minutes. The researchers found that psilocybin caused a decrease in blood flow in several areas of the brain compared to placebo. They also found that there were decreases in flow to around 16 brain areas in the cortex (the outer brain structures) and three subcortical (the inner brain structures) brain areas. The researchers plotted the decrease in blood flow against how intense the volunteers said their experience was. They found the greater the decreases in blood flow, the more intense the subjective effects. They found similar changes in activity when using the second type of functional brain scan, but additionally found decreases in activity in some areas of the brain involved in vision. The researchers say that there may be other ways the drug could have affected the blood-brain signal on the functional scans, such as by changing how the volunteers were breathing. To test this the researchers asked the volunteers to hold their breath. They found the same differences persisted between the psilocybin scan and the placebo scan, suggesting that this was not the case. How did the researchers interpret the results? The researchers say psilocybin decreased brain blood flow and oxygen levels in a manner that correlated with its subjective effects. They highlight two key brain areas that showed the decreased activity pattern: the middle prefrontal cortex and the back of the cingulate cortex. These areas are thought to play a role in decision making, social behaviour and processing emotions and memories. The researchers say that greater activity has been found to occur within the middle prefrontal cortices of people with depression, and that this activity can be reduced by treatment for depression. The authors propose that decreased activity of key brain areas with psilocybin may permit an ‘unconstrained style of cognition’. Conclusion This experimental study took functional MRI scans of 30 volunteers and looked at the differences in brain activity when they received the hallucinogenic magic mushroom extract psilocybin and when they received a placebo. They found that brain blood flow was reduced in various brain areas and that the greater the decrease in blood flow, the greater the intensity of the subjective experience of th
e volunteer when they received the hallucinogen. Although one of the brain areas that showed decreased blood flow also tends to show higher than normal activity in the brains of people with depression, this study did not directly look at the effect or possibility of using psilocybin in people with depression. Furthermore, this study recruited people who had taken hallucinogens before, so the results do not reflect the population as a whole. As this was not a clinical trial it is not possible to say from this study whether psilocybin, in combination with psychotherapy or not, would have any beneficial effect for people with depression. Also, importantly, the possible harms of using this drug, either in the short or long term, have not been studied here. TalkTalk examines Professor David Nutt’s research into psilocybin using fMRI machines. Nutt’s study was funded by MAPS and found that decreased activity of key brain areas with psilocybin may permit ‘unconstrained style of cognition’.