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First-of-its-kind study to investigate the evolution of psilocybin

A team at the University of Plymouth will be focusing on the role of psilocybin in nature.

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The Entourage Effect in Mushrooms: Natural psilocybin may outperform synthetic
Photo by Tania Malréchauffé on Unsplash

An increasing amount of research is investigating the efficacy of psychedelic mushrooms for the treatment of a number of health conditions, however, knowledge about how psychedelic compounds have evolved and their role in the natural world is limited.

To understand more about this, Scientists from the University of Plymouth are conducting a study that will harness advanced genetic methods and behavioural experiments to address previously untested hypotheses about the origin of psychedelic compounds in fungi.

This includes exploring whether such traits have evolved as a form of defence against fungus-feeding invertebrates, or whether the fungi produce compounds that manipulate insect behaviour for their own advantage.

The study is being led by a team of experienced researchers in molecular ecology, animal-plant interactions and fungal biology in the University’s School of Biological and Marine Sciences. Driving the study are Post-Doctoral Research Fellow Dr Kirsty Matthews Nicholass and Research Assistant Ms Ilona Flis.

Testing hypotheses 

The main focus will be on psilocybin. The researchers are sampling psychedelic and non-psychedelic fungi, and using next-generation DNA sequencing to test whether or not there is a diverse animal community feeding on psychedelic fungi.

Study supervisor, Dr Jon Ellis, Lecturer in Conservation Genetics, commented: “In recent years, there has been a resurgence of interest in psychedelic compounds from a human health perspective. However, almost nothing is known about the evolution of these compounds in nature and why fungi should contain neurotransmitter-like compounds is unresolved.

“The hypotheses that have been suggested for their evolution have never been formally tested, and that is what makes our project so ambitious and novel. 

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“It could also in future lead to exciting future discoveries, as the development of novel compounds that could be used as fungicides, pesticides, pharmaceuticals and antibiotics is likely to arise from ‘blue-sky’ research investigating fungal defence.”

The team will be using laboratory tests to investigate fungal-insect interactions, and whether the fungi undergo genetic changes during attack and development, as well as the effect of psilocybin on the growth of soil bacteria.

Additionally, cutting-edge gene editing technology will be used to try and create mutant fungi that cannot synthesize psilocybin. It is hoped this will help researchers better understand the role of a wide range of fungal compounds in future.

Matthews Nicholass said: “Within Psilocybe alone, there are close to 150 hallucinogenic species distributed across all continents except Antarctica. 

“Yet, the fungal species in which these ‘magic’ compounds occur are not always closely related. This raises interesting questions regarding the ecological pressures that may be acting to maintain the biosynthesis pathway for psilocybin.”

Legislation has impeded research

Researchers involved in this project have previously explored the genetic diversity among UK pollinators, the feeding preferences of slugs and snails, and developed an early warning system for plant disease.

Ellis highlights that research into psychedelic fungal compounds has been inhibited through restrictive legislation.

Ellis commented: “Fungi generally receive less attention overall than animals and plants, partly because they are less apparent, people interact with them less and they can be hard to study. 

“Historically, there have also been legal barriers which meant certain research has not previously been possible. Saying that, there were some very interesting studies in the 1940s and 50s into the use of LSD as a psychotherapeutic treatment for alcoholism and obsessive-compulsive disorder. Around that time, people also became interested in fungi from an anthropological perspective.

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“One couple, the Wassons, went to Mexico and witnessed the ritual use of fungi for the first time in religious ceremonies. Articles they published brought public attention to psychoactive mushrooms. 

“Around this time, there were also other charismatic individuals, such as Timothy Leary, who advocated the use of LSD more widely by the general public. In the 1960s, psychedelic compounds really came to widespread public attention and that ultimately led to governments introducing new laws to restrict their use.

“For some time, that also restricted the fundamental research that could be carried out. More recently, people have returned to that initial research and found that compounds such as psilocybin can have psychotherapeutic benefits. However, that has not addressed their evolution in nature, which is what makes the research we are doing so exciting.

“I hope our project can change the public perception of magic mushrooms. But beyond that, asking questions about the biological world is a fundamental part of our human nature and this project fits into a long narrative of research asking questions about biodiversity and its evolution.”

The research is being funded by the Leverhulme Trust and builds on the University’s long-running expertise in novel elements of conservation genetics.

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Landmark UK trial to investigate psilocybin for opioid addiction relapse

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For the first time, a government-funded UK trial will investigate psilocybin-assisted psychotherapy for targetting relapses associated with opioid addiction, aiming to bring an innovative new therapy to the NHS if successful. 

Research shows that the UK had the world’s highest rate of opioid consumption in 2019, amounting to a serious public health concern. Further, figures show that around 140,000 people are accessing treatment for opioid dependence in the country. Despite the prevalence of opioid addiction, there are currently limited medicines to help prevent relapses during recovery.

Led by Imperial College London, the new study will use psilocybin combined with psychological support in people who have recently undergone detoxification from opioids such as heroin, methadone or buprenorphine.

While previous research into psilocybin has shown its potential as a treatment for conditions such as depression, anxiety PTSD and addiction, this is the first trial looking at the medicine for addiction relapse.

See also  Compass Pathways launches Phase 3 psilocybin trial in UK

The study is one of four projects focused on reducing drug deaths that have been funded by the National Institute for Health and Care Research (NIHR) as part of the Addiction Healthcare Goals programme, led by the Office for Life Science (OLS). 

According to the NHIR, the programme forms part of the Department of Health and Social Care’s plan to deliver a world-class treatment and recovery system for people experiencing drug and alcohol addictions.

Dr David Erritzoe, Clinical Director and Deputy Head of the Centre for Psychedelic Research at Imperial College London, project co-lead, said in a press statement: “We know that up to 90% of people relapse back to opioid use within 12 months of finishing detox, so finding new and effective treatments is essential. 

“If this trial is successful, it offers hope for a new type of treatment that could make a significant difference to this group of people.

“If our initial trial is successful, we will work to enable the development of further clinical trials in larger populations, to bring a new treatment to patients and the NHS.”

Participants will attend Imperial’s NIHR Clinical Research Facility at Hammersmith Hospital campus to receive psilocybin-assisted psychotherapy and will receive functional MRI brain scans to enable investigation of the mechanisms of psilocybin in the brain.

Imperial has confirmed that participants will be monitored for up to six months following dosing to track any changes to their opioid use, cravings, mental health outcomes and psychological wellbeing. 

Study co-lead Dr Louise Paterson said in a press statement: “This trial will examine whether we can improve recovery in a severely under-served group of people – namely, those with opioid dependence during their most vulnerable post-detox phase. 

“Clinical studies, including those in our Centre for Psychedelic Research, have shown great promise for this type of treatment in other mental health conditions. We want to see if it works equally well for opioid use disorder.”

Professor Anne Lingford-Hughes, Chair of the Addiction Healthcare Goals, and who is also a Professor of Addiction Biology at Imperial, added: “New approaches to treat drug addiction and reduce drug-related deaths, particularly from overdose, are urgently needed. 

“The Addiction Healthcare Goals programme is pleased to fund promising innovations that have brought together partnerships between industry, academia and organisations involved in delivering treatment and care for those experiencing drug addictions.” 

Recruitment is expected to begin in Spring 2025.

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Psilocybin versus escitalopram for depression shows positive results

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Compass Pathways launches Phase 3 psilocybin trial in UK

A six-month follow-up study of a Phase 2 clinical trial investigating psilocybin versus escitalopram for the treatment of major depressive disorder has shown positive results.

Around 30% of people living with depression in the UK are resistant to current treatments, highlighting an urgent need for new therapies. As the researchers of this study highlight, even for patients who have had their depression successfully treated, there is a high risk of relapse, with one in three patients relapsing within the year.

Equally, SSRI treatments often include side effects such as sexual dysfunction, weight gain, fatigue, and emotional blunting.

The authors note that a key consideration of any treatment of major depressive disorder “is its capacity to produce sustained antidepressant response or remission.”

Mounting evidence is increasingly pointing to psilocybin-assisted therapy as an innovative new treatment for the condition, with clinical trials showing that the therapy is capable of producing rapid and long-lasting antidepressant effects.

However, while clinical trials have investigated the treatment itself, they have not compared the treatment to the current gold standard in depression medications or looked at the long-term effects of the treatment.

This Phase 2 trial is the first to compare the long-term antidepressant effects of these two treatments alongside mental health measures including work and social functioning, connectedness, and meaning in life. 

In the trial, patients with major depressive disorder recruited from a UK hospital were administered either two doses of 25mg of psilocybin along with psychological support, or a six-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram in combination with psychological support.

The findings, published in eClinicalMedicine, revealed that both administered treatments saw sustained improvements in depressive symptoms, however, patients who were administered psilocybin-assisted psychotherapy saw greater lasting improvements. 

These improvements included psychosocial functioning, meaning in life, and psychological connectedness.

Dr James Rucker, Consultant Psychiatrist & Senior Clinical Lecturer in Psychopharmacology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said: “The authors have tended to attribute differences observed in this study to comparative differences between the drugs themselves, however, it is also possible that the results reflect biased reporting between groups. 

“This is more likely here because A) studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and B) study participants were unblinded during the long-term follow-up phase that is reported in the paper, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. 

“The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe and the US.”

The authors write: “Key limitations of the study include its suboptimal power to detect small but meaningful differences between treatments, missing data, the potential use of additional interventions during the follow-up period, and reliance on self-reported treatment assessments. 

“These factors may affect the interpretation of the study findings and should be considered when evaluating the results.”

With these considerations in mind, the researchers suggest that the findings warrant further investigation into psilocybin-assisted psychotherapy for the treatment of depression.

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Shortwave Life Sciences psilocybin drug shows positive results in anorexia trial

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Shortwave Life Sciences psilocybin drug positive results anorexia trial

Shortwave Life Sciences has announced it has achieved a significant breakthrough in its ambitions to transform eating disorder care with positive pre-clinical results from its latest pharmacodynamics study, demonstrating the safety of its psilocybin-based drug combination for the treatment of anorexia nervosa.

Anorexia nervosa has one of the highest fatality rates. The condition is a complex mental health condition as well as a metabolic disease, yet no FDA-approved pharmacological treatments are currently available for the condition.

Shortwave Life Sciences in collaboration with Science in Action, an expert pre-clinical GLP-certified lab in Israel, has now tested the safety of buccal administration of Shortwave’s combination drug comprised of psilocybin and a beta-carboline.

The company says this novel treatment provides an expanded mechanism of action and a therapeutic effect superior to psilocybin alone, impacting more than one group of receptors in the brain.

For the study, three groups of rats were given varying doses of the combination drug (0.23ml, 0.5ml, and 1ml), with results showing no adverse effects, weight changes, or behavioural changes following the psychedelic effects.

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“This is a monumental step forward for Shortwave. Our relentless pursuit of breakthrough mental health treatments comes with the responsibility of ensuring safety at every stage,” commented Shortwave Life Sciences CEO Rivki Stern Youdkevich.

“We are proud of the positive outcomes from this rigorous pre-clinical trial, further validating our patent-pending drug combination and buccal delivery system.

“With this success, we are reaffirmed in our approach to addressing the global mental health crisis.”

In the pre-clinical pharmacodynamics study, all subjects remained healthy and unaffected during the trial, which Shortwave has stated marks a strong foundation for future clinical development.

Furthermore, no adverse events or vital sign changes were reported across all groups, and the results confirmed the safety profile for the psilocybin-based combination drug at elevated doses.

This achievement comes on the heels of the International PCT Examining Committee’s recent acknowledgment of Shortwave’s patent claims for its novel, non-obvious, and industrially applicable mucoadhesive buccal film.

Designed for rapid absorption and bypassing liver and gut degradation, the platform holds transformative potential for patients facing metabolic and psychiatric challenges. This method of administration is designed to be sensitive to patient needs, who may not want to swallow the medicine, and also provides higher bioavailability.

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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