Tag: psilocybin

Categories : AgeingTags :

Psilocybin Byproduct Delays Aging and Extends Lifespan, New Study Suggests

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Photo by Marek Piwnicki

As revenues from the anti-aging market – riddled with hope and thousands of supplements – surged past $500 million last year, Emory University researchers identified a compound that actively delays aging in cells and organisms.

A newly published study in Nature Partner Journals’ Aging demonstrates that psilocin, a byproduct of consuming psilocybin, the active ingredient in psychedelic mushrooms, extended the cellular lifespan of human skin and lung cells by more than 50%.

In parallel, researchers also conducted the first long-term in vivo study evaluating the systemic effects of psilocybin in aged mice of 19 months, or the equivalent of 60–65 human years. Results indicated that the mice that received an initial low dose of psilocybin of 5mg/kg, followed by a monthly high dose of 15mg/kg for 10 months, had a 30% increase in survival compared to controls. These mice also displayed healthier physical features, such as improved fur quality, fewer white hairs and hair regrowth.

While traditionally researched for its mental health benefits, this study suggests that psilocybin impacts multiple hallmarks of aging by reducing oxidative stress, improving DNA repair responses, and preserving telomere length. Telomeres are the structured ends of a chromosome, protecting it from damage that could lead to the formation of age-related diseases, such as cancer, neurodegeneration or cardiovascular disease. These foundational processes influence human aging and the onset of these chronic diseases.

The study concludes that psilocybin may have the potential to revolutionize anti-aging therapies and could be an impactful intervention in an aging population.

“Most cells in the body express serotonin receptors, and this study opens a new frontier for how psilocybin could influence systemic aging processes, particularly when administered later in life,” says Louise Hecker, PhD, senior author on the study, and former associate professor at Emory, where the research was initiated and funded.

While much of what researchers know about psilocybin relates to the brain, few studies have examined its systemic impacts. Many people associate psilocybin with the hallucinogenic impacts, but the majority of the cells in the body express serotonin receptors.

“Our study opens new questions about what long-term treatments can do. Additionally, even when the intervention is initiated late in life in mice, it still leads to improved survival, which is clinically relevant in healthy aging,” adds Hecker, currently an associate professor at Baylor College of Medicine.

Not just a longer life, but a healthier life

“This study provides strong preclinical evidence that psilocybin may contribute to healthier aging – not just a longer lifespan, but a better quality of life in later years,” says Ali John Zarrabi, MD, director of psychedelic research at Emory’s Department of Psychiatry. “As a palliative care physician-scientist, one of my biggest concerns is prolonging life at the cost of dignity and function. But these mice weren’t just surviving longer – they experienced better aging,” adds Zarrabi, co-investigator of the study. 

Zarrabi emphasises the importance of further research in older adults, as well as the well-documented overlap between physical and mental health.

“Emory is actively involved in Phase II and III clinical trials of psilocybin-assisted therapy for depression, and these results suggest we also need to understand psilocybin’s systemic effects in aging populations,” says Zarrabi. “My hope is also that if psilocybin-assisted therapy is approved as an intervention for depression by the FDA in 2027, then having a better quality of life would also translate into a longer, healthier life.”

Source: Emory Health Sciences

Categories : Mental HealthTags :

Psilocybin Dose Provides Two Years of Relief from Cancer Depression

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Phase 2 trial reveals that a single dose of psilocybin offers long-term relief from symptoms of depression and anxiety.

Photo by Marek Piwnicki: https://www.pexels.com/photo/macro-photography-of-a-psilocybin-mushroom-13695325/

New results from a clinical trial reveal that a single dose of psilocybin can provide sustained reductions in depression and anxiety in individuals with cancer suffering from major depressive disorder. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

People with cancer often struggle with depression. In this phase 2 trial, 28 patients with cancer and major depressive disorder received psychological support from a therapist prior to, during, and following a single 25mg dose of psilocybin.

During clinical interviews conducted 2 years later, 15 (53.6%) patients demonstrated a significant reduction in depression, and 14 (50%) had sustained depression reduction as well as remission. Similarly, psilocybin reduced anxiety for 12 (42.9%) patients at 2 years.

An ongoing randomised, double-blind trial is currently evaluating up to two doses of 25mg of psilocybin versus placebo as treatment for depression and anxiety in patients with cancer. This study is building on the single-dose study in an effort to bring a larger majority of the patients into remission of depression and anxiety.

“One dose of psilocybin with psychological support to treat depression has a long-term positive impact on relieving depression for as much as 2 years for a substantial portion of patients with cancer, and we’re exploring whether repeating the treatment resolves depression for more than half of the patients,” said lead author Manish Agrawal, MD, of Sunstone Therapies. “If randomised testing shows similar results, this could lead to greater use of psilocybin to treat depression in patients with cancer.”

Source: Wiley

Categories : Mental Health NeurologyTags :

Two Reasons I’m Sceptical About Psychedelic Science

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Photo by Marek Piwnicki

Michiel van Elk, Leiden University

Since I was young, I have been intrigued by altered states of consciousness, such as out-of-body experiences, paranormal phenomena and religious visions. I studied psychology and neuroscience to gain a better understanding of how these experiences come about. And in my scientific career, I have focused on the question of why some people are more prone to having these experiences than others.

Naturally, when I came across psychedelic science a couple of years ago, this field also sparked my academic interest. Here was an opportunity to study people who had a psychedelic experience and who claimed to have had a glimpse of ultimate reality. I started to research psychedelic experiences at Leiden University and founded the PRSM lab – a group of scientists from different academic backgrounds who study psychedelic, religious, spiritual and mystical experiences.

Initially, I was enthusiastic about the mind-transforming potential of psychedelics. These substances, when administered correctly, appear to be capable of enhancing people’s mental and physical wellbeing. They also increase feelings of connectedness to and concern for the environment.

Psychedelic therapy appeared to offer great potential for treating a wide variety of disorders, including depression, anxiety, addiction and post-traumatic stress disorder. This enthusiasm about the potentially transformative effects of psychedelics was reflected in positive media attention on this topic over the past few years. Michael Pollan, an American author and journalist, has brought psychedelics to an audience of millions with his book and Netflix documentary.

However, my initial optimism about psychedelics and their potential has changed into scepticism about the science behind much of the media hype. This is due to a closer scrutiny of the empirical evidence. Yes, at face value it seems as if psychedelic therapy can cure mental disease. But on closer inspection, the story is not that straightforward.

The main reason? The empirical evidence for the efficacy of and the working mechanisms underlying psychedelic therapy is far from clear.

Two issues

I wrote a critical review paper with my colleague Eiko Fried in which we listed the problems with the current clinical trials on psychedelic therapy. The main concern is called the “breaking blind problem”. In psychedelic studies, patients easily figure out if they have been randomly assigned to the psychedelic or the placebo group, simply because of the profound mind-altering effects of psychedelic substances.

This breaking-of-the-blind can actually result in placebo effect in patients in the psychedelic group: they finally get the treatment they’d been hoping for and they start feeling better. But it can also result in frustration and disappointment in patients assigned to the control group. They were hoping to get a miracle cure but now find out they will have to spend six hours on a placebo pill with their therapist.

As a consequence, any difference in therapeutic outcomes between the psychedelic and the placebo group is largely driven by these placebo and nocebo effects. (A nocebo effect is when a harmless treatment causes side-effects or worsening of symptoms because the person believes they may occur or expects them to occur.)

Knowing who received what also affects the therapists, who may be motivated to get more out of the therapy session if their patient got the “real deal”. And this problem is impossible to control for in so-called randomised controlled trials – still the gold standard in evaluating the effectiveness of drugs and treatments.

Also, non-clinical research on psychedelics faces problems. You may recall the graphic of a brain on psilocybin compared to one on a placebo (see below). Psilocybin increases the connections between different brain areas, which is represented in a colourful array of connecting lines.

This has become known as the “entropic brain hypothesis”. Psychedelics make your brain more flexible such that it returns to a child-like state of openness, novelty and surprise. This mechanism in turn has been hypothesised to underlie psychedelic therapy’s efficacy: by “liberating your brain” psychedelics can change entrenched and maladaptive patterns and behaviour. However, it turns out the picture is much more complicated than that.

Psychedelics constrict the blood vessels in your body and brain and this causes problems in the measurement of brain signals with MRI machines.

The graphic of the entropic brain may simply reflect the fact that the blood flow in the brain is dramatically altered under psilocybin. Also, it is far from clear what entropy exactly means – let alone how it can be measured in the brain.

A recent psilocybin study, which is yet to be peer-reviewed, found that only four out of 12 entropy measures could be replicated, casting further doubt on how applicable this mechanism of action is.

Although the story about psychedelics freeing your mind is compelling, it does not yet square well with the available empirical evidence.

These are just two examples that illustrate why it is important to be really cautious when you evaluate empirical studies in psychedelic science. Don’t trust findings at face value, but ask yourself the question: is the story too good or too simple to be true?

Personally, I have developed a healthy dose of scepticism when it comes to psychedelic science. I am still intrigued by psychedelics’ potential. They offer great tools for studying changes in consciousness. However, it is too early to conclude anything definite about their working mechanisms or their therapeutic potential. For this, we need more research. And I’m excited to contribute to that endeavour.

Michiel van Elk, Associate Professor, Cognitive Psychology, Leiden University

This article is republished from The Conversation under a Creative Commons license.

Read the original article.

Categories : Mental Health NeurologyTags :

Scientists may have Found out How Rapid-acting Antidepressants Work

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Rapid-acting antidepressants, including ketamine, scopolamine and psilocybin, have been found to have immediate and lasting positive effects on mood in patients with major depressive disorder but how these effects arise is unknown. New research led by the University of Bristol and published in Science Translational Medicine explored their neuropsychological effects and found that all three of these drugs can modulate affective biases associated with learning and memory.

Negative affective biases are a core feature of major depressive disorder. Affective biases occur when emotions alter how the brain processes information and negative affective biases are thought to contribute to the development and continuation of depressed mood.

The research team used an affective bias test, based on an associative learning task, to investigate the effects of rapid-acting antidepressants (RAADs) in rats.

They found that all the treatments were able to reduce negative affective biases associated with past experiences but there were additional characteristics of the dissociative anaesthetic, ketamine, and the serotonergic psychedelic, investigational COMP360 psilocybin (Compass Pathways’ proprietary formulation of synthetic psilocybin), which could explain why the effects of a single treatment can be long-lasting.

The findings suggest that these sustained effects are due to adaptive changes in the brain circuits which control affective biases, and these can influence how past experiences are remembered.

The effects at low doses were very specific to affective bias modulation and were localised to the prefrontal cortex of the brain, a region known to play an important role in mood.

Emma Robinson, Professor of Psychopharmacology in the School of Physiology, Pharmacology & Neuroscience at Bristol, and lead author, said: “Using a behavioural task we showed that drugs that are believed to have rapid and sustained benefits in depressed patients, specifically modulate affective biases associated with past experiences, something which we think is really important for understanding why they can improve a patient’s mood so quickly.

“We also found differences in how ketamine, scopolamine and COMP360 psilocybin interact with these neuropsychological mechanisms which may explain why the effects of a single treatment in human patients can be long-lasting, days (ketamine) to months (psilocybin).

“By using an animal model, we have been able to investigate these important interactions with learning and memory processes and neural plasticity and propose a two-stage model that may explain the effects we observe.”

In the task, each animal learnt to associate a specific digging material with a food reward under either treatment or control conditions.

The treatment condition is designed to generate a change in the animal’s affective state and a choice test is used to quantify the affective bias this generates.

Acute treatment with the RAADs ketamine, scopolamine, or psilocybin prevented the retrieval of the negative affective bias induced in this model.

However, the most exciting finding was at 24 hours after treatment when low, but not high, doses of ketamine and psilocybin led to a re-learning effect where the negatively biased memory was retrieved with a more positive affective valence.

Only psilocybin, but not ketamine or scopolamine treatment also positively biased new experiences.

Exploring in more detail the re-learning effects of ketamine in the studies, the researchers found they were protein synthesis-dependent, localised to the medial prefrontal cortex and could be modulated by cue-reactivation, consistent with their predictions of experience-dependent neural plasticity.

The study’s findings propose a neuropsychological mechanism that may explain both the immediate and sustained effects of RAADs, potentially linking their effects on neural plasticity with mood.

Source: University of Bristol

Categories : Mental HealthTags :

Psilocybin Shows Promise in Treatment-resistant Depression

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Photo by Timothy Dykes on Unsplash

The largest and most rigorous clinical trial to date of psilocybin (a psychoactive ingredient in magic mushrooms), suggests the possibility that COMP360 psilocybin with psychological support could be a beneficial therapeutic strategy for people with treatment-resistant depression (TRD). The trial results were published in the New England Journal of Medicine.

Prompted by promising preliminary findings, this funded multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018 to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg), compared to 1mg, with psychological support in people with TRD.

The trial, which included 233 people with TRD across 10 countries who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks. This offers hope that COMP360 psilocybin with psychological support could be an effective antidepressant treatment paradigm for some people with TRD, if proven effective and safe in larger studies. COMPASS Pathways, the company that developed the psilocybin formulation., will be running a larger phase 3 programme of COMP360 psilocybin therapy in TRD, which is on schedule to begin in 2022.

KEY RESEARCH FINDINGS

  • 25mg COMP360 psilocybin with psychological support led to a statistically and clinically significantly reduction in symptoms of depression in people with TRD compared to 1mg at week 3.
  • 37% of people with TRD in the 25mg group met criteria for response at week 3 (≥ 50% decrease in depressive symptoms).
  • Approximately 30% of people with TRD in the 25mg group met criteria for remission at week 3 (29.1%).
  • 20% of people with TRD in the 25mg group met criteria for sustained response at week 12.
  • COMP360 psilocybin was generally well-tolerated.

Dr John R. Kelly, Psychiatrist and Clinical Senior Lecturer, Trinity College said: “This is the largest and most rigorous clinical trial of psilocybin to date. It shows a promising antidepressant signal for 25mg COMP360 psilocybin with psychological support and has paved the way for phase 3 clinical trials, which will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.”

Source: Trinity College Dublin

Categories : Mental HealthTags :

‘Huge Deficit’ in Data for Psilocybin’s Interaction with Existing Medication

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As the US state of Oregon becomes the first to permit psilocybin in clinical use, a new systematic evidence review reveals a lack of scientific research describing the interactions between widely used psychiatric medications and psychedelics like psilocybin and MDMA. The review was published in the journal Psychopharmacology.

The scarcity of data is problematic for people believed to benefit most from psychedelics: those with mental health conditions such as depression, anxiety and post-traumatic stress disorder.

“There’s a huge deficit in the scientific literature,” said lead author Aryan Sarparast, MD, assistant professor of psychiatry at the Oregon Health and Science University. “There’s a major incongruence between the public enthusiasm and exuberance with psychedelic substances for mental health issues – and what happens when they combine with the existing mental health treatments that we have now.”

The researchers decided to conduct the evidence review because they wanted to learn more about interactions between widely prescribed medications such as antidepressants and psychedelics, including MDMA and psilocybin.

They found a total of 40 studies dating back to 1958, including 26 from randomised controlled studies, 11 case reports and three epidemiologic studies.

Only one study was found that examined how psilocybin interacts with antidepressant medications. A/Prof Sarparast also noted that all of the clinical trials were conducted with healthy volunteers who were administered a psychiatric medication and a psychedelic at the same time – clearly showing a need for further research into combining pharmaceutical medications with psilocybin.

A/Prof Sarparast said he is concerned that the lack of evidence will lead many providers to direct patients to taper off existing medications before being offered clinical psilocybin therapy. In Oregon rules are being drawn up to permit the clinical use of psilocybin products and services from next year.

Patients with mental health conditions might well benefit from psilocybin therapy, but A/Prof Sarparast said he is concerned about the implications of stopping existing psychiatric treatment in order to receive psilocybin services. Vulnerable people may end up being forced into choosing between their existing medical treatment or psilocybin services.

“That’s a very, very tough place to be,” A/Prof Sarparast said.

A considerable amount of important data exists that is not captured in a literature review related to real-world use, noted co-author Christopher Stauffer, MD, assistant professor of psychiatry in the OHSU School of Medicine and a physician-scientist at the VA Portland Health Care System.

“Psilocybin has been around in Western society since the late 1950s, before many of our psychiatric medications have existed,” A/Prof Stauffer said. “Nonetheless, people attempting to navigate Oregon’s psilocybin services in the context of ongoing psychiatric treatment should work closely with knowledgeable professionals.”

Source: Oregon Health & Science University

Categories : Mental HealthTags :

Psychedelic Compound Treats Depression by Growing Neural Connections

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In a new study, researchers have shown that a single dose of psilocybin, a psychedelic compound with potential applications for depression, prompted long-lasting increase in connections between neurons in mice. 

For some people, psilocybin, an active compound in ‘magic mushrooms’, can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the Americas and is also a popular recreational drug. It has been the subject of some interest in treating depression. But exactly how it works in the brain and how long beneficial results might last is still unclear.
“We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” reported senior author Alex Kwan, associate professor of psychiatry and of neuroscience at Yale.

Earlier work had found promising evidence that psilocybin, as well as the anaesthetic ketamine, could decrease depression. This new study found that these compounds increase the density of dendritic spines, which are small protrusions found on nerve cells which aid in the transmission of information between neurons. The number of these neuronal connections are known to be reduced by chronic stress and depression.


Prof Kwan and first author Ling-Xiao Shao, a postdoctoral associate, imaged dendritic spines in high resolution with a laser-scanning microscope, and tracked them for multiple days in living mice. They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still evident a month later. Also, mice subjected to stress showed behavioural improvements and increased neurotransmitter activity after being given psilocybin.

It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections, Kwan said.

“It was a real surprise to see such enduring changes from just one dose of psilocybin,” he said.  “These new connections may be the structural changes the brain uses to store new experiences.”

Source: Yale University