Mindfulness meditation enhances positive effects of psilocybin

October 24, 2019

Science Daily/University of Zurich

Recent years have seen a renewed interest in the clinical application of classic psychedelics in the treatment of depression and anxiety disorders. Researchers of the University of Zurich have now shown that mindfulness meditation can enhance the positive long-term effects of a single dose of psilocybin, which is found in certain mushrooms.

Hallucinogens such as LSD or psilocybin, the active ingredient in "magic mushrooms," alter the perception of those who take them: The boundaries between the self and the world begin to dissolve and feelings of bliss and unity are triggered. Such experiences of self-transcendence and reduced self-focus are similar to those brought about by mindfulness meditation. They can reduce stress, prompt feelings of enduring happiness and increase empathy and altruism. In contrast to this, exaggerated self-focus, recurring negative thoughts and emotions about one's self, and impaired social interactions are characteristic features of psychiatric disorders such as depression.

Enhanced experience of self-transcendence

Researchers at the University Hospital of Psychiatry Zurich have now for the first time examined the potential synergistic effects of combining mindfulness meditation and psilocybin. The scientists recruited 40 meditation experts who were taking part in a five-day mindfulness retreat. In the double-blind study, the participants were administered either a single dose of psilocybin or a placebo on the fourth day of the group retreat. Using various psychometric and neurocognitive measurements, the team of researchers were able to show that mindfulness meditation increased the positive effects of psilocybin, while counteracting possible dysphoric responses to the psychedelic experience. "Psilocybin markedly increased the incidence and intensity of self-transcendence virtually without inducing any anxiety compared to participants who received the placebo," says first author Lukasz Smigielski, who conducted the study directed by UZH professor of psychiatry Franz Vollenweider.

Sustained beneficial effects

At the four-month follow-up, the meditation experts who had been given psilocybin demonstrated more beneficial changes in psychosocial functioning, better self-acceptance and more empathy than the placebo control group. According to Vollenweider, the intensity of self-transcendence experienced during the retreat played a key role for these enduring changes. In a previously published study, he and his team used magnetic resonance imaging to show that experiences of self-transcendence result in lasting changes to neural connections in the brain, and more specifically in the regions that are active when we think about ourselves.

The research group found that besides meditation depth, the participants' openness and optimism were conducive to a positive response to psilocybin. "These factors can help us predict a positive response," says Vollenweider. At the same time, skills that are trained during mindfulness meditation -- such as regulating one's attention and reappraising emotions -- seem to buffer potential negative reactions to psilocybin.

Potential for treating affective disorders

"Our findings shed light on the interplay between pharmacological and extra-pharmacological factors in psychedelic states of mind," says Vollenweider. "They indicate that mindfulness training enhances the positive effects of a single dose of psilocybin, and can increase empathy and permanently reduce ego-centricity. This opens up new therapeutic avenues, for example for the treatment of depression, which is often accompanied by increased self-focus and social deficits."

https://www.sciencedaily.com/releases/2019/10/191024075003.htm

Can tiny doses of magic mushrooms unlock creativity?

Preliminary study suggests that 'microdoses' of psychedelics may enhance a person's creative problem solving abilities

October 25, 2018

Science Daily/Springer

The use of minute doses of magic mushrooms and truffles containing psychedelic substances could induce a state of unconstrained thought that may produce more new, creative ideas. "Microdosing" in this way may allow people to experience the creative benefits of psychedelic drugs without the risk of the so-called "bad trips" that often come with high doses of such substances. This is according to a new study in the Springer-branded journal Psychopharmacology which is the official journal of the European Behavioural Pharmacology Society (EBPS). The research was led by Luisa Prochazkova of Leiden University in The Netherlands and is the first study of its kind to experimentally investigate the cognitive-enhancing effects of microdosing on a person's brain function within a natural setting.

Taking a tiny fraction of a normal dose of psychedelic substances is becoming a trend in some professional circles because this is thought to stimulate brain function and enhance mental flexibility and creativity. However, experimental research that moves away from anecdotal evidence is still rare.

In this study, Prochazkova and her colleagues investigated how a microdose of a psychedelic substance affected the cognitive brain function of 36 people who were present at an event organized by the Psychedelic Society of The Netherlands. During the experimental phase, participants were set three tasks before and after they consumed on average 0.37 grams of dried truffles. The tests assessed their convergent thinking (the identification of a single solution to a problem), their fluid intelligence (the capacity to reason and solve new problems) and their divergent thinking (the ability to recognize many possible solutions). Afterwards, the researchers analyzed the active substances present in the truffles consumed by participants.

After taking the microdose of truffles, the researchers found that participants' convergent thinking abilities were improved. Participants also had more ideas about how to solve a presented task, and were more fluent, flexible and original in the possibilities they came up with. Microdosing with psychedelic substances therefore improved both the divergent and convergent thinking of participants.

These findings are in line with earlier studies that found high doses of psychedelics can enhance creative performance. The fact that participants' intelligence scores and general analytical abilities did not change suggests that the effect of the truffles is rather selective, and more to the benefit of a person's creative domain.

"Taken together, our results suggest that consuming a microdose of truffles allowed participants to create more out-of-the-box alternative solutions for a problem, thus providing preliminary support for the assumption that microdosing improves divergent thinking," explains Prochazkova. "Moreover, we also observed an improvement in convergent thinking, that is, increased performance on a task that requires the convergence on one single correct or best solution."

Prochazkova hopes that these findings will stimulate further research into the beneficial effects of microdosing psychedelics. "Apart from its benefits as a potential cognitive enhancement technique, microdosing could be further investigated for its therapeutic efficacy to help individuals who suffer from rigid thought patterns or behavior such as individuals with depression or obsessive-compulsive disorder," she explains.

https://www.sciencedaily.com/releases/2018/10/181025103329.htm

Reclassification recommendations for drug in 'magic mushrooms'

Reclassification recommendations for drug in 'magic mushrooms'

If phase III clinical trials are successful, researchers suggest categorizing the drug as schedule IV

September 26, 2018

Science Daily/Johns Hopkins Medicine

In an evaluation of the safety and abuse research on the drug in hallucinogenic mushrooms, Johns Hopkins researchers suggest that if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug -- one with no known medical potential -- to a schedule IV drug such as prescription sleep aids, but with tighter control.

 The researchers summarize their analysis in the October print issue of Neuropharmacology.

 "We want to initiate the conversation now as to how to classify psilocybin to facilitate its path to the clinic and minimize logistical hurdles in the future," says Matthew W. Johnson, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We expect these final clearance trials to take place in the next five years or so."

Following the Controlled Substances Act of 1970, any drug with the potential for abuse is categorized based on criteria that take into account whether the drug has accepted medical use, and its safety and the potential for abuse. Although preliminary research studies suggest that psilocybin may be effective for smoking cessation and for disorders such as cancer-specific depression and anxiety, it must clear phase III clinical trials before the Food and Drug Administration can be petitioned to reclassify it.

Studies in animals and humans both show low potential for abuse, the researchers say. When rats push a lever to receive psilocybin, they don't keep pushing the lever like they do for drugs such as cocaine, alcohol or heroin. When it comes to human studies, people who have used psilocybin typically report using it a few times across their lifetime.

As for safety, studies show it frequently falls at the end of the scales with the least harm to users and society, say the researchers. Psilocybin also is lowest in the potential for lethal overdose as there is no known overdose level.

"We should be clear that psilocybin is not without risks of harm, which are greater in recreational than medical settings, but relatively speaking, looking at other drugs both legal and illegal, it comes off as being the least harmful in different surveys and across different countries," says Johnson.

That being said, although psilocybin is relatively less harmful than other drugs and not prone to compulsive abuse, the researchers don't recommend releasing psilocybin into patients' hands even with a prescription. "We believe that the conditions should be tightly controlled and that when taken for a clinical reason, it should be administered in a health care setting monitored by a person trained for that situation," says Johnson. The researchers foresee that the process for psilocybin use in the clinic would be similar to how an anesthesiologist prescribes and administers a drug, minimizing the potential for abuse or harm.

https://www.sciencedaily.com/releases/2018/09/180926082159.htm

Why are some mushrooms 'magic?'

Study offers evolutionary explanation, could pave way for neurological treatments

February 27, 2018

Science Daily/Ohio State University

The work helps explain a biological mystery and could open scientific doors to studies of novel treatments for neurological disease, said lead researcher Jason Slot, an assistant professor of fungal evolutionary genomics at The Ohio State University.

Mushrooms that contain the brain-altering compound psilocybin vary widely in terms of their biological lineage and, on the surface, don't appear to have a whole lot in common, he said.

From an evolutionary biology perspective, that is intriguing and points to a phenomenon in which genetic material hops from one species to another -- a process called horizontal gene transfer, Slot said. When it happens in nature, it's typically in response to stressors or opportunities in the environment.

He and his co-authors examined three species of psychedelic mushrooms -- and related fungi that don't cause hallucinations -- and found a cluster of five genes that seem to explain what the psychedelic mushrooms have in common.

"But our main question is, 'How did it evolve?'" Slot said. "What is the role of psilocybin in nature?"

Slot and his co-authors found an evolutionary clue to why the mushrooms gained the ability to send human users into a state of altered consciousness. The genes responsible for making psilocybin appear to have been exchanged in an environment with a lot of fungus-eating insects, namely animal manure.

Psilocybin allows fungi to interfere with a neurotransmitter in humans and also insects, which are probably their bigger foe. In flies, suppression of this neurotransmitter is known to decrease appetite.

"We speculate that mushrooms evolved to be hallucinogenic because it lowered the chances of the fungi getting eaten by insects," Slot said. The study appears online in the journal Evolution Letters.

"The psilocybin probably doesn't just poison predators or taste bad. These mushrooms are altering the insects' 'mind' -- if they have minds -- to meet their own needs."

And the reason that unrelated species have the same genetic protection probably comes down to the fact that they commonly grow in the same insect-rich mediums: animal feces and rotten wood.

This work could guide medical science by pointing researchers in the direction of other molecules that could be used to treat disorders of the brain, Slot said.

Psilocybin has been studied for the treatment of a variety of mental disorders, including treatment-resistant depression, addiction and end-of-life anxiety. A handful of researchers in the U.S. are looking at potential treatment applications, and much of the work is happening abroad. Strict drug laws have delayed those types of studies for decades, Slot said.

https://www.sciencedaily.com/releases/2018/02/180227115548.htm

Psychedelic drugs may reduce criminal behavior

Illicit substances may be effective interventions to crime

October 23, 2017

Science Daily/University of British Columbia Okanagan campus

Newly published research suggests that common psychedelic drugs -- such as magic mushrooms, LSD and mescaline (a substance derived from the peyote cactus) -- may reduce criminal offences.

The new study, co-authored by UBC Okanagan's Associate Professor of Psychology Zach Walsh, found that psychedelic drugs are associated with a decreased likelihood of antisocial criminal behaviour.

"These findings add to a growing body of research suggesting that use of classic psychedelics may have positive effects for reducing antisocial behaviour," said Walsh, a p. "They certainly highlight the need for further research into the potentially beneficial effects of these stigmatized substances for both individual and public health."

Lead author, University of Alabama Assoc. Prof. Peter Hendricks, used data obtained by the National Survey on Drug Use and Health, which is administered by the U.S. Department of Health and Human Services, to explore the connection between the use of classic psychedelic substances and criminal behaviour among more than 480,000 American adult respondents from the past 13 years.

Key findings of the study are that respondents who have used psychedelic drugs had 27 per cent decreased odds of larceny or theft, and 22 per cent decreased odds of arrest for a violent crime in the past year. At the same time, lifetime use of other illicit substances was generally associated with increased odds of criminal behaviour.

Hendricks says that psilocybin and related compounds could revolutionize the mental health field.

"The development of innovative and effective interventions to prevent criminal behaviour is an obvious priority," Hendricks adds. "Our findings suggest the protective effects of classic psychedelic use are attributable to genuine reductions in antisocial behaviour rather than reflecting improved evasion of arrest. Simply put, the positive effects associated with classic psychedelic use appear to be reliable. Given the costs of criminal behaviour, the potential represented by this treatment paradigm is significant."

Walsh points out that research on the benefits of psychedelic drugs started decades ago, primarily to treat mental illness. However, it was stopped due to the reclassification of the drugs to controlled substances in the mid-1970s. Recent years have seen a resurgence of interest in psychedelic medicine.

"More research is needed to figure out what factors underlie these effects," Walsh says. "But the experiences of unity, positivity and transcendence that characterize the psychedelic experience may have lasting benefits that translate into real-world consequences."

The research was recently published by the Journal of Psychopharmacology.

https://www.sciencedaily.com/releases/2017/10/171023101753.htm

'Magic mushrooms' may 'reset' the brains of depressed patients

October 13, 2017

Science Daily/Imperial College London

Patients taking psilocybin to treat depression show reduced symptoms weeks after treatment following a 'reset' of their brain activity.

The findings come from a study in which researchers from Imperial College London used psilocybin -- the psychoactive compound that occurs naturally in magic mushrooms -- to treat a small number of patients with depression in whom conventional treatment had failed.

In a paper, published today in the journal Scientific Reports, the researchers describe patient-reported benefits lasting up to five weeks after treatment, and believe the psychedelic compound may effectively reset the activity of key brain circuits known to play a role in depression.

Comparison of images of patients' brains before and one day after they received the drug treatment revealed changes in brain activity that were associated with marked and lasting reductions in depressive symptoms.

The authors note that while the initial results of the experimental therapy are exciting, they are limited by the small sample size as well as the absence of a control group -- such as a placebo group -- to directly contrast with the patients.

Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial, who led the study, said: "We have shown for the first time clear changes in brain activity in depressed people treated with psilocybin after failing to respond to conventional treatments.

"Several of our patients described feeling 'reset' after the treatment and often used computer analogies. For example, one said he felt like his brain had been 'defragged' like a computer hard drive, and another said he felt 'rebooted'. Psilocybin may be giving these individuals the temporary 'kick start' they need to break out of their depressive states and these imaging results do tentatively support a 'reset' analogy. Similar brain effects to these have been seen with electroconvulsive therapy."

Over the last decade or so, a number of clinical trials have been conducted into the safety and effectiveness of psychedelics in patients with conditions such as depression and addictions, yielding promising results.

In the recent Imperial trial, the first with psilocybin in depression, 20 patients with treatment-resistant form of the disorder were given two doses of psilocybin (10 mg and 25 mg), with the second dose a week after the first.

Nineteen of these underwent initial brain imaging and then a second scan one day after the high dose treatment. Carhart-Harris and team used two main brain imaging methods to measure changes in blood flow and the crosstalk between brain regions, with patients reporting their depressive symptoms through completing clinical questionnaires.

Immediately following treatment with psilocybin, patients reported a decrease in depressive symptoms -- corresponding with anecdotal reports of an 'after-glow' effect characterised by improvements in mood and stress relief.

Functional MRI imaging revealed reduced blood flow in areas of the brain, including the amygdala, a small, almond-shaped region of the brain known to be involved in processing emotional responses, stress and fear. They also found increased stability in another brain network, previously linked to psilocybin's immediate effects as well as to depression itself.

These findings provide a new window into what happens in the brains of people after they have 'come down' from a psychedelic, where an initial disintegration of brain networks during the drug 'trip', is followed by a re-integration afterwards.

Dr Carhart-Harris explained: "Through collecting these imaging data we have been able to provide a window into the after effects of psilocybin treatment in the brains of patients with chronic depression. Based on what we know from various brain imaging studies with psychedelics, as well as taking heed of what people say about their experiences, it may be that psychedelics do indeed 'reset' the brain networks associated with depression, effectively enabling them to be lifted from the depressed state.

The authors warn that while the initial findings are encouraging, the research is at an early stage and that patients with depression should not attempt to self-medicate, as the team provided a special therapeutic context for the drug experience and things may go awry if the extensive psychological component of the treatment is neglected. They add that future studies will include more robust designs and currently plan to test psilocybin against a leading antidepressant in a trial set to start early next year.

Professor David Nutt, Edmond J. Safra Professor of Neuropsychopharmacology and director of the Neuropsychopharmacology Unit in the Division of Brain Sciences, and senior author of the paper, added: "Larger studies are needed to see if this positive effect can be reproduced in more patients. But these initial findings are exciting and provide another treatment avenue to explore."

https://www.sciencedaily.com/releases/2017/10/171013091018.htm

Magic enzymes in 'magic' mushrooms analyzed

Enzymatic synthesis of psilocybin, the ingredient of magic mushrooms

August 25, 2017

Science Daily/Wiley

Little fungi pack a punch: "Magic mushrooms" of the Psilocybe species produce psychoactive compounds that alter perception when ingested. Recently, the effects on the neuronal system caused by their ingredient psilocybin have attracted the interest of pharmacologists. German scientists have now identified four of the enzymes responsible for the biosynthesis of psilocybin. In the journal Angewandte Chemie, they describe the biosynthetic pathway and introduce a synthetic route that could form the basis of biotechnological production.

For centuries, Central American cultures considered Psilocybe mushrooms to be divine and used them for spiritual purposes. More recently, they have been called magic mushrooms and used for their hallucinogenic effects. These mushroom drugs may soon also be in use as pharmaceuticals that treat the existential anxiety of advanced-stage cancer patients, depression, and nicotine addiction. Their effects stem from tryptamines, which are chemical derivatives of the amino acid L-tryptophan and structural relatives of the neurotransmitters serotonin and melatonin. Among these, psilocybin is the primary chemical mushroom component. Psilocybin is an inactive precursor that is rapidly activated when consumed: splitting off a phosphate group results in the actual active ingredient, psilocin.

Although the structure of psilocybin has been known for about 60 years, it has not been possible to decode the enzymatic basis of its biosynthesis. Researchers working with Dirk Hoffmeister at the Friedrich Schiller University of Jena have now figured this out. They have identified the four enzymes that transform the amino acidy L-tryptophan into psilocybin. Using genetic technology, the researchers were able to produce the enzymes in bacterial and mould fungi cultures and characterize them.

Based on this knowledge, they were also able to clarify the biosynthetic production route, which is different than previously supposed. In the first step of the biosynthesis, an unsusual type of tryptophan decarboxylase splits the carboxyl group off of the amino acid L-tryptophan. A monooxygenase then introduces an alcohol group, to which a kinase subsequently adds a phosphate group. Finally, a methyl transferase adds two methyl groups stepwise to the amino group.

Starting with 4-hydroxy-L-tryptophan and using three of the four fungal enzymes, the scientists were able to enzymatically synthesize psilocybin by a simple method in a combined reaction. Given the pharmaceutical industry's renewed interest in psilocybin, these results may lay the foundation for its biotechnological production.

https://www.sciencedaily.com/releases/2017/08/170825103955.htm

Biological basis for magic mushroom 'mind expansion' discovered

July 3, 2014

Science Daily/Imperial College London

New research shows that our brain displays a similar pattern of activity during dreams as it does during a mind-expanding drug trip. The study found that under psilocybin, activity in the more primitive brain network linked to emotional thinking became more pronounced, with several different areas in this network -- such as the hippocampus and anterior cingulate cortex -- active at the same time. This pattern of activity is similar to the pattern observed in people who are dreaming.

Psychedelic drugs such as LSD and magic mushrooms can profoundly alter the way we experience the world but little is known about what physically happens in the brain. New research, published in Human Brain Mapping, has examined the brain effects of the psychedelic chemical in magic mushrooms, called psilocybin, using data from brain scans of volunteers who had been injected with the drug.

The study found that under psilocybin, activity in the more primitive brain network linked to emotional thinking became more pronounced, with several different areas in this network -- such as the hippocampus and anterior cingulate cortex -- active at the same time. This pattern of activity is similar to the pattern observed in people who are dreaming. Conversely, volunteers who had taken psilocybin had more disjointed and uncoordinated activity in the brain network that is linked to high-level thinking, including self-consciousness.

Psychedelic drugs are unique among other psychoactive chemicals in that users often describe 'expanded consciousness,' including enhanced associations, vivid imagination and dream-like states. To explore the biological basis for this experience, researchers analysed brain imaging data from 15 volunteers who were given psilocybin intravenously while they lay in a functional magnetic resonance imaging (fMRI) scanner. Volunteers were scanned under the influence of psilocybin and when they had been injected with a placebo.

"What we have done in this research is begin to identify the biological basis of the reported mind expansion associated with psychedelic drugs," said Dr Robin Carhart-Harris from the Department of Medicine, Imperial College London. "I was fascinated to see similarities between the pattern of brain activity in a psychedelic state and the pattern of brain activity during dream sleep, especially as both involve the primitive areas of the brain linked to emotions and memory. People often describe taking psilocybin as producing a dream-like state and our findings have, for the first time, provided a physical representation for the experience in the brain."

The new study examined variation in the amplitude of fluctuations in what is called the blood-oxygen level dependent (BOLD) signal, which tracks activity levels in the brain. This revealed that activity in important brain networks linked to high-level thinking in humans becomes unsynchronised and disorganised under psilocybin. One particular network that was especially affected plays a central role in the brain, essentially 'holding it all together', and is linked to our sense of self.

In comparison, activity in the different areas of a more primitive brain network became more synchronised under the drug, indicating they were working in a more co-ordinated, 'louder' fashion. The network involves areas of the hippocampus, associated with memory and emotion, and the anterior cingulate cortex which is related to states of arousal.

Lead author Dr Enzo Tagliazucchi from Goethe University, Germany said: "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."

Dr. Carhart-Harris added: "Learning about the mechanisms that underlie what happens under the influence of psychedelic drugs can also help to understand their possible uses. We are currently studying the effect of LSD on creative thinking and we will also be looking at the possibility that psilocybin may help alleviate symptoms of depression by allowing patients to change their rigidly pessimistic patterns of thinking. Psychedelics were used for therapeutic purposes in the 1950s and 1960s but now we are finally beginning to understand their action in the brain and how this can inform how to put them to good use."

The data was originally collected at Imperial College London in 2012 by a research group led by Dr Carhart-Harris and Professor David Nutt from the Department of Medicine, Imperial College London. Initial results revealed a variety of changes in the brain associated with drug intake. To explore the data further Dr. Carhart-Harris recruited specialists in the mathematical modelling of brain networks, Professor Dante Chialvo and Dr Enzo Tagliazucchi to investigate how psilocybin alters brain activity to produce its unusual psychological effects.

As part of the new study, the researchers applied a measure called entropy. This was originally developed by physicists to quantify lost energy in mechanical systems, such as a steam engine, but entropy can also be used to measure the range or randomness of a system. For the first time, researchers computed the level of entropy for different networks in the brain during the psychedelic state. This revealed a remarkable increase in entropy in the more primitive network, indicating there was an increased number of patterns of activity that were possible under the influence of psilocybin. It seemed the volunteers had a much larger range of potential brain states that were available to them, which may be the biophysical counterpart of 'mind expansion' reported by users of psychedelic drugs.

Previous research has suggested that there may be an optimal number of dynamic networks active in the brain, neither too many nor too few. This may provide evolutionary advantages in terms of optimising the balance between the stability and flexibility of consciousness. The mind works best at a critical point when there is a balance between order and disorder and the brain maintains this optimal number of networks. However, when the number goes above this point, the mind tips into a more chaotic regime where there are more networks available than normal. Collectively, the present results suggest that psilocybin can manipulate this critical operating point.

The research was funded and intellectually supported by the Beckley Foundation. Professor Chialvo is from the Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Argentina and Dr Tagliazucchi is based at Goethe University, Germany.

https://www.sciencedaily.com/releases/2014/07/140703102649.htm

Psilocybin inhibits the processing of negative emotions in the brain

May 7, 2014

Science Daily/University of Zurich

Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role -- above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.

Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could "point the way to novel approaches to treatment" comments the lead author Rainer Krähenmann on the results which have now been published in the medical journal Biological Psychiatry.

Psilocybin inhibits the processing of negative emotions in the amygdala

The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann's research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.

Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). "Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions," continues Krähenmann. The study clearly shows that the modulation of amygdalaactivity is directly linked to the experience of heightened mood.

Next study with depressive patients

According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressed patients -- and may consequently lead to improved mood in these patients. .

Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.

https://www.sciencedaily.com/releases/2014/05/140507095756.htm

Evolutionary relationships among species of 'magic' mushrooms shed light on fungi

August 6, 2013

Science Daily/Canadian Science Publishing (NRC Research Press)

"Magic" mushrooms are well known for their hallucinogenic properties. Until now, less has been known about their evolutionary development and how they should be classified in the fungal Tree of Life. New research helps uncover the evolutionary past of a fascinating fungi that has wide recreational use and is currently under investigation for a variety of medicinal applications.

In the 19th century, the discovery of hallucinogenic mushrooms prompted research into the mushrooms' taxonomy, biochemistry, and historical usage. Gastón Guzmán, a world authority on the genus Psilocybe, began studying its taxonomy in the 1950s. In 1983, these studies culminated in a monograph, which is currently being updated as a team of researchers from the University of Guadalajara and the University of Tennessee collaborate with Guzmán to produce a hypothesis on how these mushrooms evolved. Some of their latest research is now published in the journal Botany.

Using new molecular and computational techniques, the team has produced the first multi-gene evaluation of the evolutionary development of Psilocybe, which constitutes a major step in classifying and naming "magic" mushrooms. Earlier work showed that species of Psilocybe did not commonly descend from a single ancestor. As a result, the hallucinogenic species (the genus Psilocybe) were typically separated from their non-hallucinogenic relatives (the genus Deconica). But this new work now places the two separate monophyletic -- meaning developed from a single ancestor -- groups into different families. Within Psilocybe (family Hymenogastraceae) and Deconica (family Strophariaceae s.str), the authors have discovered several strong infrageneric relationships.

According to the authors, their analysis of various morphological traits of the mushrooms suggests that these typically weren't acquired through a most recent common ancestor and must have evolved independently or undergone several evolutionary losses, probably for ecological reasons. Nevertheless, species of Psilocybe are united to some degree because they have the psychedelic compound psilocybin and other secondary metabolites, or products of metabolism. The authors say that former Psilocybe species that lack these secondary metabolites could also be found in Deconica.

https://www.sciencedaily.com/releases/2013/08/130806132852.htm

First trial to investigate magic mushrooms as a treatment for depression delayed by UK and EU regulations

April 7, 2013

Science Daily/British Neuroscience Association

The world's first clinical trial to explore the use of the hallucinogenic ingredient in magic mushrooms to treat depression is being delayed due to the UK and EU rules on the use of illegal drugs in research.

Professor David Nutt, president of the British Neuroscience Association and Professor of Neuropsychopharmacology at Imperial College London (UK), will tell the BNA's Festival of Neuroscience today (Sunday) that although the UK's Medical Research Council has awarded a grant for the trial, the Government's regulations controlling the licensing of illegal drugs in research and the EU's guidelines on Good Manufacturing Practice (GMP) have stalled the start of the trial, which was expected to start this year. He is calling for a change to the regulations.

He will tell the meeting at the Barbican in London, that his research has shown that psilocybin, the psychedelic ingredient in magic mushrooms, has the potential to alleviate severe forms of depression in people who have failed to respond fully to other anti-depressant treatments. However, psilocybin is illegal in the UK; the United Nations 1971 Convention on Psychotropic Substances classifies it as a Schedule 1 drug, one that has a high potential for abuse with no recognised medical use, and the UK has classified it as a Class A drug, the classification used for the most dangerous drugs. This means that a special licence has to be obtained to use magic mushrooms in research in the UK, and the manufacture of a synthetic form of psilocybin for use in patients is tightly controlled by EU regulations.

Prof Nutt will say: "The law for the control of drugs like psilocybin as a Schedule 1 Class A drug makes it almost impossible to use them for research and the reason we haven't started the study is because finding companies who could manufacture the drug and who are prepared to go through the regulatory hoops to get the licence, which can take up to a year and triple the price, is proving very difficult. The whole situation is bedevilled by this primitive, old-fashioned attitude that Schedule 1 drugs could never have therapeutic potential, and so they have to be made impossible to access."

"The knock-on effect is this profound impairment of research. We are the first people ever to have done a psilocybin study in the UK, but we are still hunting for a company that can manufacture the drug to GMP standards for the clinical trial, even though we've been trying for a year to find one. We live in a world of insanity in terms of regulating drugs at present. The whole field is so bogged down by these intransient regulations, so that even if you have a good idea, you may never get it into the clinic."

He will say that the regulations need to be changed. "Even if I do this study and I show it's a really useful treatment for some people with depression, there's only four hospitals in this country that have a licence to hold this drug, so you couldn't roll out the treatment if it worked because the regulations would make it difficult to use," he said.

Prof Nutt and his team at Imperial College London (UK) have shown that when healthy volunteers are injected with psilocybin, the drug switched off a front part of the brain called the anterior cingulate cortex, which is known from previous imaging studies to be over-active in depression. "We found that, even in normal people, the more that part of the brain was switched off under the influence of the drug, the better they felt two weeks later. So there was a relationship between that transient switching off of the brain circuit and their subsequent mood," he will explain. "This is the basis on which we want to run the trial, because this is what you want to do in depression: you want to switch off that over-active part of the brain.

"The other thing we discovered is that the major site of action of the magic mushrooms is to turn down a circuit in the brain called the 'default mode network', which the anterior cingulate cortex is part of. The default mode network is a part of the brain between the front and back. It is active when you are thinking about you; it coordinates the thinking and emotional aspects of you."

The researchers discovered that the 'default mode network' had the highest density of 5HT2A receptors in the brain. These are known to be involved in depression and are the targets for a number of existing anti-depressive drugs that aim to improve levels of serotonin -- the neurotransmitter [1] that gives people a sense of well-being and happiness. Psilocybin also acts on these receptors.

"We have found that people with depression have over-active default mode networks, and they are continually locked into a mode of thinking about themselves. So they ruminate on themselves, on their incompetencies, on their badness, that they're worthless, that they've failed; these things are not true, and sometimes they reach delusional levels. This negative rumination may be due to a lack of serotonin and what psilocybin is doing is going in and rapidly replacing the missing serotonin, switching them back into a mind state where they are less ruminating and less depressed," Prof Nutt will say.

The proposed trial will be for patients with depression who have failed two previous treatments for the condition. Thirty patients will be given a synthetic form of psilocybin and 30 patients will be given a placebo. The drug (or placebo) will be given during two, possibly three, carefully controlled and prepared 30-60 minute sessions. The first session will be a low dose to check there are no adverse responses, the second session will give a higher, therapeutic dose, and then patients can have a third, booster dose in a later session if it's considered necessary. While they are under the influence of the drug, the patients will have guided talking therapy to enable them to explore their negative thinking and issues that are troubling them. The doctors will follow up the patients for at least a year.

"What we are trying to do is to tap into the reservoir of under-researched 'illegal' drugs to see if we can find new and beneficial uses for them in people whose lives are often severely affected by illnesses such as depression. The current legislation is stopping the benefits of these drugs being explored and for the last 40 years we have missed really interesting opportunities to help patients."

Ethical approval for the trial was granted in March and Prof Nutt says he hopes to be able to start the trial within the next six months -- so long as he can find a manufacturer for the drug.

[1] Neurotransmitters are chemicals that transmit signals from neurons (nerve cells) to target cells.

[2] Funding: The Beckley Foundation has funded part of Prof Nutt's research, and the Medical Research Council has agreed a grant for the proposed clinical trial.

Abstract title: "Can we use psychedelic drugs to treat depressions?" Symposium: "Treating depression with antidepressants: where are we now and where are we going?"

https://www.sciencedaily.com/releases/2013/04/130407090832.htm

Magic mushrooms' effects illuminated in brain imaging studies

January 24, 2012

Science Daily/Imperial College London

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 January 23 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 January 24, 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.

The studies were carried out with a Home Office licence for storing and handling a schedule 1 drug and were approved by NHS research ethics committees. All the volunteers were mentally and physically healthy and had taken hallucinogenic drugs previously without any adverse response. The research involved scientists from Imperial, the University of Bristol and Cardiff University and was funded by the Beckley Foundation, the Neuropsychoanalysis Foundation, Multidisciplinary Association for Psychedelic Studies, and the Heffter Research Institute.

https://www.sciencedaily.com/releases/2012/01/120123152043.htm

Single dose of 'magic mushrooms' hallucinogen may create lasting personality change

September 29, 2011

Science Daily/Johns Hopkins Medical Institutions

A single high dose of the hallucinogen psilocybin, the active ingredient in so-called "magic mushrooms," was enough to bring about a measurable personality change lasting at least a year in nearly 60 percent of the 51 participants in a new study, according to the Johns Hopkins researchers who conducted it.

Lasting change was found in the part of the personality known as openness, which includes traits related to imagination, aesthetics, feelings, abstract ideas and general broad-mindedness. Changes in these traits, measured on a widely used and scientifically validated personality inventory, were larger in magnitude than changes typically observed in healthy adults over decades of life experiences, the scientists say. Researchers in the field say that after the age of 30, personality doesn't usually change significantly.

"Normally, if anything, openness tends to decrease as people get older," says study leader Roland R. Griffiths, a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

The research, approved by Johns Hopkins' Institutional Review Board, was funded in part by the National Institute on Drug Abuse and published in the Journal of Psychopharmacology.

The study participants completed two to five eight-hour drug sessions, with consecutive sessions separated by at least three weeks. Participants were informed they would receive a "moderate or high dose" of psilocybin during one of their drug sessions, but neither they nor the session monitors knew when.

During each session, participants were encouraged to lie down on a couch, use an eye mask to block external visual distraction, wear headphones through which music was played and focus their attention on their inner experiences.

Personality was assessed at screening, one to two months after each drug session and approximately 14 months after the last drug session. Griffiths says he believes the personality changes found in this study are likely permanent since they were sustained for over a year by many.

Nearly all of the participants in the new study considered themselves spiritually active (participating regularly in religious services, prayer or meditation). More than half had postgraduate degrees. The sessions with the otherwise illegal hallucinogen were closely monitored and volunteers were considered to be psychologically healthy

"We don't know whether the findings can be generalized to the larger population," Griffiths says.

As a word of caution, Griffiths also notes that some of the study participants reported strong fear or anxiety for a portion of their daylong psilocybin sessions, although none reported any lingering harmful effects. He cautions, however, that if hallucinogens are used in less well supervised settings, the possible fear or anxiety responses could lead to harmful behaviors.

Griffiths says lasting personality change is rarely looked at as a function of a single discrete experience in the laboratory. In the study, the change occurred specifically in those volunteers who had undergone a "mystical experience," as validated on a questionnaire developed by early hallucinogen researchers and refined by Griffiths for use at Hopkins. He defines "mystical experience" as among other things, "a sense of interconnectedness with all people and things accompanied by a sense of sacredness and reverence."

Personality was measured on a widely used and scientifically validated personality inventory, which covers openness and the other four broad domains that psychologists consider the makeup of personality: neuroticism, extroversion, agreeableness and conscientiousness. Only openness changed during the course of the study.

Griffiths says he believes psilocybin may have therapeutic uses. He is currently studying whether the hallucinogen has a use in helping cancer patients handle the depression and anxiety that comes along with a diagnosis, and whether it can help longtime cigarette smokers overcome their addiction.

"There may be applications for this we can't even imagine at this point," he says. "It certainly deserves to be systematically studied."

Along with the National Institute on Drug Abuse, this study was funded by the Council on Spiritual Practices, Heffter Research Institute and the Betsy Gordon Foundation.

Other Hopkins authors of the research include Matthew W. Johnson, Ph.D, and Katherine A. MacLean, Ph.D.

https://www.sciencedaily.com/releases/2011/09/110929074205.htm