Showing posts sorted by relevance for query Psilocybin. Sort by date Show all posts
Showing posts sorted by relevance for query Psilocybin. Sort by date Show all posts

Monday, October 23, 2023

Single dose of psilocybin reduces depression in phase 2 trial

Credit: Cannabis_Pic / Adobe Stock

OCTOBER 22, 2023

Can psilocybin serve as a uniquely powerful and long-lasting treatment for depression? Since the renaissance of psychedelic research emerged in the 2000s, a growing body of studies suggests that psilocybin can reduce symptoms of conditions like major depressive disorder, anxiety, and end-of-life distress.

The most intriguing findings center on dosage: Some studies suggest that a single dose of psilocybin can yield therapeutic benefits that last long after the drug’s hallucinogenic effects wear off, possibly even months after ingesting one dose.

A study recently published in JAMA sheds new light on the therapeutic potential of psilocybin for depression. The randomized, double-blind phase 2 trial, conducted between 2019 and 2022, investigated the effects of a single dose of synthetic psilocybin on people with major depressive disorder.

The researchers found that “a 25-mg dose of psilocybin administered with psychological support was associated with a rapid and sustained antidepressant effect, measured as change in depressive symptom scores, compared with active placebo.”

Here are some of the key takeaways:The recent study featured a sample size of 104 people and a longer follow-up period than many previous studies on psilocybin and depression.
The participants who received psilocybin showed significantly reduced depressive symptoms compared to those who received a placebo, though they also experienced more adverse events.

The improvements in depression were sustained over a six-week follow-up period.

“These findings add to evidence that psilocybin—when administered with psychological support—may hold promise as a novel intervention for [major depressive disorder],” the researchers noted.

The results are promising, though they come with a couple of caveats.
A closer look at psilocybin and depression

For the study, the researchers recruited a total of 104 adult participants with moderate to severe major depressive disorder. After participants were given time, if needed, to stop psychotherapy and taper off any antidepressant medications they were taking, the researchers randomly sorted them into two groups.

One group of 51 people were assigned to get a single dose of psilocybin. The other group of 54 participants were given a placebo: niacin, a B vitamin that causes your face to “flush.” (The idea is that this reaction might make it harder for people to tell whether they got the drug or the placebo.) At the start of the study, neither the researchers nor the participants were told who received the psilocybin. Also, participants were given multiple sessions of psychological support, including during the psilocybin (or niacin) experience.

The main goal of the study was not to see whether depression decreased while people were experiencing the effects of psilocybin but rather to track changes in depressive symptoms in both groups at various timeframes over a six-week follow-up period. To do that, the researchers measured participants’ scores on the Montgomery-Asberg Depression Rating Scale (MADRS), which assesses the severity of depressive episodes. The researchers also had participants complete the Sheehan Disability Scale (SDS), which measures how symptoms impair functioning in daily life.

Participants completed both scales before taking either the psilocybin or the placebo, referred to as their baseline score, and also at follow-up periods: 2, 8, 15, 29, and 43 days after dosing.

The results revealed a statistically significant difference between the two groups in terms of reduced depressive symptoms over the six-week period. The group that got psilocybin saw their MADRS scores decline by an average of 19.1 points, vs. 6.8 points in the placebo group

.
A chart from the study showing changes in depression symptoms over time in the psilocybin and placebo groups. Credit: Raison CL, Sanacora G, Woolley J, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023;330(9):843–853. doi:10.1001/jama.2023.14530

By day 43, 58% of participants in the psilocybin group demonstrated a sustained response (defined as a 50% reduction from their baseline score), compared to 20% of the placebo group.

Although a sustained response is a good sign that an antidepressant is effective, it’s not the same as sustained remission, where depressive symptoms drop into the “normal” range. (While a greater share of the psilocybin group did go into remission compared to placebo, the difference wasn’t statistically significant.)

When it came to safety and tolerability, the researchers wrote, “Psilocybin was generally well-tolerated, with most AEs [adverse events] being of mild or moderate severity and generally limited to the acute dosing period.” However: “psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs compared with niacin, with these severe AEs being known effects of psilocybin.”
Caveats and cautious optimism

It’s worth noting that not all participants stuck with the follow-ups. The placebo group had a higher dropout rate, with 44 of the initial 53 participants ultimately making it to the 43-day check-up. Meanwhile, all but one participant in the psilocybin group completed the study (one withdrew from the study due to a death in their family).

What explains the difference in dropout rates? It’s hard to say for sure, but one possibility is that people in the placebo group became less motivated to participate in the study because they knew they received niacin instead of psilocybin. This underscores what’s arguably the biggest problem with psychedelic research: complications with blinding.

To validate the therapeutic potential of any drug, researchers use randomized placebo-controlled trials, where some participants receive the drug while others receive a placebo. Ideally, this process is double blinded, meaning neither the participants nor the researchers know who received the drug until the study concludes. The goal is to minimize bias and ensure that any recorded effects are likely due to the drug itself and not participants’ or researchers’ expectations.

But psychedelics make blinding nearly impossible: If you take psilocybin — a hallucinogenic drug that radically alters your subjective experience of reality — you’re unlikely to mistake it for a B vitamin.

Expectation biases — whether in the participants, the researchers, or both — can also complicate psychedelic research. For example, people who agree to participate in studies on drugs like psilocybin, MDMA, or LSD might already have a strong belief that psychedelics can effectively treat mental health conditions.

“This is likely to lead to positive expectation (consciously, subconsciously or both) which is in turn likely to lead to improvements in symptoms after enrollment, regardless of the specific effects of the psychedelics,” noted a 2022 paper published in Psychopharmacology. “This effect also works conversely, in that positive expectations can fuel disappointment in trials of novel psychoactive medication when participants believe that they have been allocated to the placebo arm.”

Still, the results of the recent study are promising, and they add to a growing body of research showing that psilocybin and other psychedelics might possess therapeutic effects that can far outlast the trip experience itself. Considering that 29% of U.S. adults report having been diagnosed with depression at some point in their lives, it’s arguably well worth exploring how psychedelics might help ease the burden of mental health problems.

So far, Oregon and Colorado are the only US states that have legalized psychedelic-assisted therapy, though initiatives in a handful of other states — California, Connecticut, and New Jersey — have aimed to pass similar legislation. Earlier in 2023, Australia became the first country to legalize the prescription of psychedelics, including psilocybin, for mental health conditions.

This article was originally published by our sister site, Freethink.


Thursday, July 16, 2020

Magic mushroom compound provides anti-anxiety and antidepressant effects lasting years, study finds

Single dose of psilocybin leads to decreased demoralisation and improved spiritual wellbeing among cancer sufferers, long-term research indicates


Harry Cockburn
Tuesday 28 January 2020

A single dose of psilocybin, a compound found in psychedelic mushrooms, can result in “significant improvements” in reducing stress and anxiety in cancer patients for as long as five years after it was administered, a new study suggests.

A research team at New York University‘s Grossman School of Medicine, who were following up a landmark 2016 study into psilocybin, found that in conjunction with psychotherapy, cancer patients experienced improvements in emotional and existential distress.

In the earlier study, the team reported that the use of psilocybin produced “immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralisation and hopelessness, improved spiritual wellbeing, and increased quality of life”.

After a follow-up assessment, six-and-a-half months later, psilocybin was associated with “enduring anti-anxiety and antidepressant effects”.

The new study — a long term follow up of the same set of patients — found the positive effects had continued.

“Participants overwhelmingly (71 to 100 per cent) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives,” the researchers said

“Adding to evidence dating back as early as the 1950s, our findings strongly suggest that psilocybin therapy is a promising means of improving the emotional, psychological, and spiritual wellbeing of patients with life-threatening cancer,” said the 2016 parent study’s lead investigator, Dr Stephen Ross.

“This approach has the potential to produce a paradigm shift in the psychological and existential care of patients with cancer, especially those with terminal illness.”

The researchers said psilocybin could become a useful tool for enhancing the effectiveness of psychotherapy and ultimately relieving these symptoms.

Although the precise mechanisms are not fully understood, scientists believe the drug can make the brain more flexible and receptive to new ideas and thought patterns. In addition, previous research indicates the drug targets a network of the brain, the default mode network, which becomes activated when we engage in self-reflection and mind wandering, and which helps to create our sense of self and sense of coherent narrative identity.

‘Absurd’ magic mushrooms and MDMA are class A drugs, expert tells MPs

In patients with anxiety and depression, this network becomes hyperactive and is associated with rumination, worry, and rigid thinking. Psilocybin appears to acutely shift activity in this network and helps people to take a more broadened perspective on their behaviours and lives.

The follow-up study is the longest-spanning exploration of psilocybin’s effects on cancer-related psychiatric distress to date, the authors say.

“These results may shed light on how the positive effects of a single dose of psilocybin persist for so long,” said Gabby Agin-Liebes, lead author of the long-term follow-up study.

“The drug seems to facilitate a deep, meaningful experience that stays with a person and can fundamentally change his or her mindset and outlook,” she said.

The research is published in the Journal of Psychopharmacology.


Magic mushroom compound psilocybin found safe for consumption in largest ever controlled study

‘Clinically reassuring’ results boost development of psychoactive ingredient as depression treatment, researcher says



Andy Gregory
Wednesday 18 December 2019 

The largest controlled study of psilocybin – the psychoactive ingredient in magic mushrooms – has found the compound safe for human consumption, bringing researchers one step closer to developing a psilocybin-based treatment for depression.

Volunteers who received doses of the psychedelic compound experienced no serious adverse effects in phase one clinical trials at Kings College London (KCL).

Psilocybin has been tipped as a potentially groundbreaking treatment for mental health disorders that could replace antidepressants, with some research suggesting it could also aid those dealing with addiction.

“The results of the study are clinically reassuring and support further development of psilocybin as a treatment for patients with mental health problems that haven’t improved with conventional therapy, such as treatment-resistant depression,” said KCL’s Dr James Rucker, the study’s lead investigator.

Most of the minor adverse events recorded were of the expected psychedelic nature, researchers found, with changes to sensory perception and mood, but no negative effects on cognitive and emotional functioning.

The phase one trials – which sought to test the compound’s safety, not its therapeutic value – compared the effects of varying doses of the psilocybin-based drug COMP360 and placebos in 89 healthy volunteers

There were 25 dosing sessions in total. In each session, six participants would receive either 10mg or 25mg doses or a placebo during a one-on-one session with a therapist lasting roughly six hours, with a follow-up period of 12 weeks.​

Research by the company behind the trial, Compass Pathways, into using psilocybin as a treatment for depression has been fast-tracked in the US, receiving special “breakthrough therapy” status from the Food and Drug Administration.

Watch more

Magic mushrooms ‘could be replacing antidepressants within five years’

It is currently running phase two studies across Europe and North America involving 216 patients who suffer with depression that hasn’t responded to treatment.

“This study is part of our overall clinical development programme in treatment-resistant depression,” Compass Pathways’ co-founder Dr Ekaterina Malievskaia said.

“We wanted to look at the safety and tolerability profile of our psilocybin, and to look at the feasibility of a model where up to six one-to-one sessions are held at the same time.

“We are focused on getting psilocybin therapy safely to as many patients who would benefit from it as possible [and] are grateful to the many pioneering research institutions whose work over the years has helped to demonstrate the potential of psilocybin in medicine.”

In June, The Independent reported that participants in the first trial comparing psilocybin to antidepressants at the world’s first psychedelic research centre, at Imperial College London, described a cathartic emotional “release” and “reconnection” during psilocybin therapy.

As the study’s lead Dr Robin Carhart-Harris pointed out, this is the polar opposite of antidepressants, which patients often complain leave their emotions “blunted”.

Friday, July 01, 2022

Bill to legalize ‘magic mushrooms’ in N.J. rolled out by Senate president

2022/6/30 
© Advance Local Media LLC.
Senate President Nicholas Scutari unveiled a new bill on June 23 that would legalize the use of psilocybin, aka "Magic Mushrooms," to treat mental health disorders. 
Photo by Emily Bingham | MLive.com

A year and a half ago, Gov. Phil Murphy signed a law authored by state Sen. Nicholas Scutari that reduced the penalties for possession of psilocybin, the active ingredient in so-called magic mushrooms, in New Jersey.

Now Scutari, who has since become Senate president, wants to legalize the psychedelic drug for adults to treat depression, anxiety, and other disorders in the state.

As the state Legislature was wrapping up details of a new $50.6 billion state budget last week, Scutari, D-Union, introduced a new bill that would set up a legal, regulatory, and therapeutic framework for using psilocybin to treat mental health in the state.

The bill, S2934, called the Psilocybin Behavioral Health Access and Services Act, would make it legal for New Jersey adults 21 and older to “possess, store, use, ingest, inhale, process, transport, deliver without consideration, or distribute without consideration, four grams or less of psilocybin.”

Adults would also be allowed to grow, cultivate and process plants or fungi capable of producing psilocybin for personal use as long as they keep it away from minors.

“This bill is a recognition of evolving science related to psilocybin and its medical uses related to mental health, and if science can provide relief in any fashion with this natural substance under a controlled environment then we should encourage this science,” Scutari told NJ Advance Media.

Some psychedelic drug experts said this is a progressive proposal that takes psilocybin policy reform to the next level.

An insert in the New Jersey bill that allows home grow of psilocybin mushrooms is drawing comparisons to cannabis.

Only licensed operators can grow cannabis in New Jersey — even for medical use — which puts the psilocybin bill ahead on that front.

“I think it’s a very good idea that you can cultivate mushrooms at home, and I support cultivation of cannabis at home,” Noah Potter, principle at Legal Market Strategies, a New York psychedelic sector consulting firm. “It doesn’t make any sense to include criminal prohibitions when cultivating a naturally occurring substance.”

Potter said there was a contradiction in permitting psilocybin cultivation from home and not cannabis.

“The question is, `What’s the rationale — other than trying to protect the for-profit commercial sector?” said Potter.

It’s a question others say could surface as the mushrooms bill advances through Trenton — much like the massive cannabis bill that Gov. Phil Murphy signed in February 2021 after a five year journey. New Jersey launched legal weed on April 21. So far 16 locations are selling adult weed with at least three more dispensaries pending: Verano in Neptune, Ascend in Montclair and TerrAscend in Lodi.

“This is an extremely progressive bill,” said Potter. “It reflects the evolution of state level psilocybin bills since 2019.”

Dan McKillop, a partner at Scarinci Hollenbeck who co-chairs the Psychedelics Law Subcommittee of the New Jersey State Bar Association, noted the connection between legalizing marijuana and legalizing magic mushrooms.

“Psychedelic law is where cannabis was a half dozen years ago, following an inevitable trend into the mainstream legal use,” said McKillop. “It is interesting the way it’s (Scutari’s bill) set up. There are a lot of similarities to the way the adult use cannabis market is being constructed and is now being implemented.”

McKillop also noted the eye-catching home grow provision.

“This bill not only decriminalizes and expunges past offenses involving psilocybin, but it also actually at least opens the door towards a home grow aspect,” said McKillop. “It goes beyond the cannabis bill and the cannabis program.”

Scutari, the chief architect of both the state’s medical marijuana and adult recreational adult cannabis laws, inserted an amendment to reduce penalties on mushrooms to the marijuana decriminalization measure in late 2020. But backers decided to sever the psilocybin legislation from the marijuana legalization measure and make them two separate bills. The bills passed in both chambers by huge majorities.

Murphy signed the mushroom bill into law on Feb. 4, 2021, that reclassified possession of psilocybin as a disorderly-persons offense from a third-degree crime in New Jersey. With that law, possession of a small amount subjects individuals to a maximum fine of $1,000 and up to six months in prison.

Psilocybin policy reform started in state legislatures in 2019 and gained steam as the psychedelic earned some credibility.

The federal Food and Drug Administration designated the psychedelic as a “breakthrough therapy” for treating major depressive disorder based on preliminary clinical trials.

Oregon voters approved a historic ballot initiative in 2020 to make psilocybin legal for adults. A bill in the California State Legislature would legalize psilocybin possession and distribution in specified amounts.

Scutari’s new psilocybin measure calls for the development of an 18-member Psilocybin Behavioral Health Access and Services Advisory Board within the New Jersey Department of Health. The board would “provide advice and recommendations to the (Department of Health), upon request or upon the board’s own initiative, concerning the implementation of the bill,” according to the legislation.

“It’s a bold and needed step in the right direction; albeit somewhat confusing considering we still have not addressed cannabis home grow and re-sentencing for the associated drug manufacturing charge,” said attorney Beau Huch, former senior aide to Sen. Declan O’Scanlon, R-Monmouth, who worked on both medical and recreational cannabis bills.

But McKillop is predicting the bill could start a new round of dialogue.

“If the home grow provision of the psilocybin bill survives the legislative process and is actually enacted into law, folks who are arguing for home grown cannabis would have a stronger argument,” said McKillop.

The 50-page bill was referred to the Senate Health, Human Services and Senior Citizens Committee, which will likely take it up in the fall.

It would need to be passed by the Democratic-controlled state Senate and Assembly and signed by Murphy, a Democrat, to become law.

Suzette Parmley may be reached at sparmley@njadvancemedia.com or follow her on Twitter: @SuzParmley

Monday, October 04, 2021

“Magic mushroom” anti-depressive psychedelic affects perception of music


Reports and Proceedings

EUROPEAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY

Scientists have found that the psychedelic drug psilocybin, in development as an anti-depressive treatment, changes the emotional state of people listening to music. Psilocybin is the active psychedelic ingredient in ‘magic mushrooms’. Clinical trials of psilocybin generally use selected music playlists to support the drug-induced psychedelic experience, and this work shows that enhanced emotional processing may be a positive outcome of combining psilocybin with music, suggesting that music should be an active component of psilocybin therapy.   This work is presented at the ECNP Congress in Lisbon.

There has been considerable interest in the use of psychedelics in the treatment of hard-to-treat depression and other mental health conditions. Psilocybin, found naturally in several species of mushrooms, is the psychedelic most suitable for clinical development, in part because the psilocybin ‘trip’ can be contained within a working day, which is important for a supervised clinical treatment.  In the treatment of depression, psilocybin is normally administered with psychological support, and with accompanying music. Previous studies have shown that the psychedelic LSD interacts with music*, and of course in the 1960’s psychedelics were intimately related to the experience of music for many. Now for the first time a group of Danish scientists have shown that psilocybin affects the way that music elicits emotions.

In the study, 20 healthy participants (50% women) were tested on their emotional response to music before and after given psilocybin; 14 of these participants were also tested after being given ketanserin (ketanserin is an anti-hypertension drug, commonly used to as a comparison in psychedelic experiments). Whether ketanserin or psilocybin was given first was randomly selected and each person was thus able to report on the changes effected by both psilocybin and ketanserin. At the peak of drug effects participants listened to a short music programme and rated their emotional response.

The emotional response to the music was rated according to the Geneva Emotional Music Scale.  The music used was a short programme comprising Elgar’s Enigma Variations no 8 and 9, and Mozart’s Laudate Dominum, together lasting around 10 minutes.

According to lead researcher, Associate Professor Dea Siggaard Stenbæk (University of Copenhagen):

“We found that psilocybin markedly enhanced the emotional response to music, when compared to the response before taking the drugs. On the measurement scale we used, psilocybin increased the emotional response to music by around 60%. This response was even greater when compared to  ketanserin.  In fact, we found that ketanserin lessens the emotional response to music. This shows that combination of psilocybin and music has a strong emotional effect, and we believe that this will be important for the therapeutic application of psychedelics if they are approved for clinical use. Psilocybin is under development as a drug to treat depression, and this work implies that music needs to be considered as a therapeutic part of the treatment.

Our next step is to look at the effect of music on the brain while under the influence of psilocybin in data material we have already collected, using an MRI”.

She continued:

“Interestingly, some of the music we used, Elgar famous ‘Nimrod’ variation (the 9th variation) describes his close friend Augustus Jaeger. Jaeger encouraged Elgar to write the variations as a way out of depression, so we’re pleased to see it used again to help understand more about mental health”.

Commenting, Professor David J Nutt (Imperial College, London) said:

“This is further evidence of the potential of using music to facilitate treatment efficacy with psychedelics. What we need to do now is optimise this approach probably through individualising and personalising music tracks in therapy”.

This is an independent comment; Professor Nutt was not involved in this work  

There is evidence that Magic mushrooms have been taken by humans for over 6000 years. Psilocybin was first isolated and synthesised in 1958, by the Swiss Chemist Albert Hoffman, the same man who first synthesised LSD. There was extensive early research into medical uses of psychedelics, but this became difficult after the US introduced a ban on their use in 1970. https://www.scientificamerican.com/article/end-the-ban-on-psychoactive-drug-research/ for background.

*See: LSD enhances the emotional response to music, Kaelen et al, Psychopharmacology 232, 3607–3614 (2015). https://link.springer.com/article/10.1007/s00213-015-4014-y

The 34th ECNP Annual conference takes place in Lisbon and online from 2-5 October, see https://www.ecnp.eu/Congress2021/ECNPcongress . The European College of Neuropsychopharmacology is Europe’s main organisation working in applied neuroscience.

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Thursday, November 03, 2022

Largest trial to date shows that COMP360 psilocybin reduces depression symptoms

Peer-Reviewed Publication

KING'S COLLEGE LONDON

A multicentre clinical trial led by COMPASS Pathways across 22 international sites including Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust has found that a single 25mg dose of COMP360 psilocybin, alongside psychological support, had a significant impact in reducing symptoms of depression in participants with treatment-resistant depression. 

Approximately 100 million people in the world suffer with treatment-resistant depression, which means they have not responded to at least two antidepressant treatments for their major depressive disorder.

The study, published in the New England Journal of Medicine, investigated the change from baseline in the severity of depression, as assessed using the Montgomery–Ã…sberg Depression Rating Scale, in participants with treatment-resistant depression over the course of 12 weeks following a single dose of COMP360 psilocybin alongside psychological support.  Researchers found that participants reported a greater reduction in depression scores three weeks after taking a single 25 mg dose of COMP360 psilocybin compared to those who took the lowest 1 mg dose.

Some adverse effects, such as headaches, nausea, dizziness, fatigue, and thoughts around suicide, were reported across all dose groups.

 

This phase 2b clinical trial was conducted at 22 sites in 10 countries across Europe (Czech Republic, Denmark, Germany, Ireland, the Netherlands, Portugal, Spain, and the United Kingdom) and North America (Canada and the United States) between 1 March 2019 and 27 September 2021. 233 participants with treatment-resistant depression were allocated at random to receive a single 25 mg, 10 mg, or 1 mg dose of COMP360 psilocybin, along with psychological support; with those who received the 1 mg dose acting as a control group.  Neither the participants nor the researchers were aware which dose the participant had received.

 

Dr James Rucker, Consultant Psychiatrist & Lead for the Psychoactive Trials Group at IoPPN, at King’s College London and South London and Maudsley NHS Foundation Trust, who took part in the research said:

‘Whilst many patients with mental health problems get better with available treatments, a subgroup of patients do not even though they try many different forms of treatment. This is sometimes called ‘treatment resistance’. This can lead to a variety of other problems that seriously impact on patients and the people around them. Treatment options are often limited, coming with troublesome side effects and/or stigma. Therefore, new paradigms of treatment are needed, and clinical research of new treatments is important. Psilocybin therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials. We are doing this work at the Psychoactive Trials Group, and we deliver new and pioneering treatments in collaboration with our colleagues at the Maudsley Centre for Advanced Treatments.’

‘This study, which is by far the largest clinical trial on the use of psilocybin for treatment-resistant depression to date, demonstrated that a single 25 mg dose of psilocybin improved participants’ symptoms of depression in comparison to a 1 mg dose (control). These findings are a positive step in the right direction. Our task now is to investigate psilocybin for treatment-resistant depression in larger clinical trials with more participants, comparing it both to placebo and to established treatments.’ 

 

‘The publication of our COMP360 psilocybin therapy study in the most prestigious peer-reviewed medical journal in the world is a proud moment for everyone involved,’ said Professor Guy Goodwin, Chief Medical Officer, COMPASS Pathways. ‘We saw positive results in a particularly difficult to treat group of patients, and the highest dose of COMP360 psilocybin had the greatest impact on people’s depression. This suggests that COMP360 psilocybin has a true pharmacological effect, a finding that is critical for it to be recognised as a new treatment option in the future. We look forward to starting our phase 3 programme later this year, moving us closer to providing COMP360 psilocybin with psychological support for patients who desperately need it.’

All participants were assessed on the severity of their depressive symptoms the day before the COMP360 psilocybin was administered, and follow up assessments were conducted on day two, and weeks one, three, six, nine, and 12.

 

Participants were given COMP360 psilocybin in specialised rooms designed to provide a nonclinical and calming atmosphere. The psychedelic effects lasted between 6 to 8 hours, and during this time an experienced therapist was in the room to provide psychological support. All therapists underwent a detailed training programme designed for the trial. After the psychedelic effects were fully dissipated participants were able to return home.

 

Researchers found that participants who received the 25 mg dose of COMP360 psilocybin, with psychological support, experienced a rapid and greater reduction in depression scores than those who received the 1 mg control dose (p<0.001).

 

 

Over the 12-week study period adverse effects, including headache, nausea, dizziness, and fatigue, occurred in 84% of participants in the 25 mg dose group, 75% in the 10 mg dose group, and 72% in the 1 mg dose group.  Suicidal ideation and intentional self-injury were seen in all dose groups, as is common in treatment-resistant depression studies. Most cases occurred more than a week after the COMP360 psilocybin session. There was no mean worsening of suicidal ideation scores on the MADRS scale in any dose group. Suicidal behaviours were reported at least one month after COMP360 administration for three non-responders in the 25mg group.

The trial was designed and funded by COMPASS Pathways. It was conducted in collaboration with the Psychoactive Trials Group at the IoPPN and the South London and Maudsley NHS Foundation Trust.

 

Ends

For further information please contact: Patrick O’Brien, Senior Media Officer, IoPPN King’s College London Tel: +44 7813706151 Em: patrick.1.obrien@kcl.ac.uk

‘Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression’ Goodwin et al is published in New England Journal of Medicine on 2 November 2022 5pm ET/9pm GMT DOI: 10.1056/NEJMoa2206443

Link to publication when embargo lifts http://www.nejm.org/doi/full/10.1056/NEJMoa2206443

 

About King’s College London

King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.

 

The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain. 

 

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on TwitterInstagramFacebook and LinkedIn

 

About COMPASS Pathways         

 

COMPASS Pathways plc (Nasdaq: CMPS) is a mental health care company dedicated to accelerating patient access to evidence-based innovation in mental health. Our focus is on improving the lives of those who are suffering with mental health challenges and who are not helped by current treatments. We are pioneering the development of a new model of psilocybin therapy, in which our proprietary formulation of synthetic psilocybin, COMP360, is administered in conjunction with psychological support. COMP360 has been designated a Breakthrough Therapy by the US Food and Drug Administration (FDA) and has received Innovative Licensing and Access Pathway (ILAP) designation in the UK for treatment-resistant depression (TRD). We have completed a phase 2b clinical trial of psilocybin therapy for TRD, in 22 sites across Europe and North America. This was the largest randomised, controlled, double-blind psilocybin therapy clinical trial ever conducted, and our topline data showed a statistically significant (p<0.001) and clinically relevant improvement in depressive symptom severity after three weeks for patients who received a single high dose of COMP360 psilocybin with psychological support. We are also running phase 2 clinical trials of COMP360 psilocybin therapy for post-traumatic stress disorder (PTSD) and anorexia nervosa. COMPASS is headquartered in London, UK, with offices in New York and San Francisco in the US. Our vision is a world of mental wellbeing. www.compasspathways.com

Tuesday, January 09, 2024

 

Largest diversity study of ‘magic mushrooms’ investigates the evolution of psychoactive psilocybin production


Peer-Reviewed Publication

UNIVERSITY OF UTAH

Holotype specimen of Psilocybe subtropicalis. 

IMAGE: 

HOLOTYPE SPECIMEN OF PSILOCYBE SUBTROPICALIS.

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CREDIT: ELIZA PETERSON/NATIONAL HISTORY MUSEUM OF UTAH




Psilocybe fungi, known colloquially as “magic mushrooms,” have held deep significance in Indigenous cultures of Mesoamerica for centuries. They captured the wider world’s attention as a psychedelic staple in the 60s and 70s. Now, these infamous organisms are at the forefront of a mental health revolution. Psilocybin and psilocin, the psychoactive compounds found in nearly all species of Psilocybe, have shown promise as a treatment for conditions including PTSD, depression, and for easing end-of-life care.

To utilize psilocybin as a therapeutic, scientists need an extensive roadmap of the compound’s underlying genetics and evolution, information that doesn’t exist. Our limited knowledge comes from research on just a fraction of the ~165 known species of Psilocybe. Most psilocybin-producing mushrooms haven’t been studied since they were first discovered—until now.

A team of researchers led by the University of Utah and the Natural History Museum of Utah (NHMU) has completed the largest genomic diversity study for the genus Psilocybe. Their genomic analysis of 52 Psilocybe specimens includes 39 species that have never been sequenced.

The authors found that Psilocybe arose much earlier than previously thought—about 65 million years ago, right around when the dinosaur-killing asteroid caused a mass extinction event. They established that psilocybin was first synthesized in mushrooms in the genus Psilocybe, with four to five possible horizontal gene transfers to other mushrooms from 40 up to 9 million years ago.

Their analysis revealed two distinct gene orders within the gene cluster that produces psilocybin. The two gene patterns correspond to an ancient split in the genus, suggesting two independent acquisitions of psilocybin in its evolutionary history. The study is the first to reveal such a strong evolutionary pattern within the gene sequences underpinning the psychoactive proteins synthesis.

“If psilocybin does turn out to be this kind of wonder drug, there’s going to be a need to develop therapeutics to improve its efficacy. What if it already exists in nature?” said Bryn Dentinger, curator of mycology at NHMU and senior author of the study. “There’s a wealth of diversity of these compounds out there. To understand where they are and how they’re made, we need to do this kind of molecular work to use biodiversity to our advantage.”

All the study’s Psilocybe DNA came from specimens in museum collections around the world. Twenty-three of the 52 specimens were “type specimens,” the gold standard designating a species against which all other samples are measured. For example, say you identify a wild mushroom as a certain species of chanterelle—you’re betting that the mushroom you picked is the same as the physical material sitting in a box in a museum. The authors’ molecular work on type species is a major contribution to mycology because it establishes an authoritative foundation for all future work on Psilocybe diversity in taxonomy.

“These type specimens represent hundreds of years of thousands of scientists’ collective effort to document diversity, way before people were thinking about DNA,” said Alexander Bradshaw, postdoctoral researcher at the U and lead author of the study. “That’s the beauty of it—no one has really sequenced type specimens at this scale, and now we get to produce molecular and genomic data to the gold standard of Psilocybe types for people to compare against.”

The study published in the journal Proceedings of the National Academy of Sciences on Jan. 9, 2024.

A trip through time

Previous studies identified the cluster of four core genes that produce psilocybin based on genomic analysis of threePsilocybe species. The species were closely related to each other, and all had matching gene patterns within the psilocybin-producing gene clusters. This study’s expanded genomics of 52 specimens of Psilocybe revealed a second distinct pattern. 

“This work represents a big step in the understanding of the evolutionary relationships in Psilocybe because it is the first to include a broad species sampling and is based on type specimens,” said Virginia Ramírez-Cruz, mycologist at the Universidad de Guadalajara and co-lead author of the study.

The authors found that 17 specimens had the original order, while 35 exhibited the new pattern.

“We’ve shown here that there’s been a lot of change in gene order over time, and that provides some new tools for biotechnology. If you’re looking for a way to express the genes to produce the psilocybin and related compounds, you no longer have to rely on only one set of gene sequences to do that. Now there’s tremendous diversity that scientists can look at for lots of different properties or efficiencies,” said Dentinger, who is also an associate professor of biology at the University of Utah.

Dating of the group showed that an ancient split of the two gene cluster patterns occurred around 57 million years ago, which also corresponded to a shift in the ecology. The first psilocybin-producing mushrooms likely arose as a wood-decomposing group, then transitioned to soil after the split, with some species such as Psilocybe cubensis transiting to growing on herbivore dung. The ecological shift to dung appears to have occurred at least twice independently in their evolutionary history. 

What does psilocybin do for mushrooms?

The authors hoped that psilocybin’s evolutionary history would clarify the most basic question—what does psilocybin do for mushrooms? The psilocybin-producing gene clusters likely have some benefit, but no one knows what it is.

The molecular structure of psilocybin mimics serotonin and binds tightly to serotonin receptors, especially at 5-HT2A, a famous receptor onto which many psychedelic drugs bind. When a chemical binds to these receptors in mammals and similar ones in insects and arachnids, they produce unnatural and altered behaviors. Some have proposed that this altered mental state might be a direct deterrent to predation. It’s also possible that psilocybin functions as a laxative or induces vomiting to spread spores before they are fully digested. However, psilocybin mushrooms often occur infrequently in the wild, making it unlikely that animals could learn to recognize them. An alternative theory is that psilocybin is a chemical defense against insects. However, empirical studies are lacking, and the authors’ personal observations confirm that psilocybin-containing mushrooms regularly host healthy, thriving insect larvae.

The authors are preparing experiments to test an alternative theory that they call the Gastropod Hypothesis. The timing and divergence dates of Psilocybe coincide with the KPg boundary, the geological marker of the asteroid that threw Earth into a brutal, prolonged winter and killed 80% of all life. Two lifeforms that thrived during the darkness and decay were fungi and terrestrial gastropods. Evidence, including the fossil record, shows that gastropods had a massive diversification and proliferation just after the asteroid hit, and it’s known that terrestrial slugs are heavy predators of mushrooms. With the study’s molecular dating of Psilocybe to around 65 million years ago, it’s possible that psilocybin evolved as a slug deterrent. They hope that their feeding experiments will shed some light on their hypothesis.

In 2020, the authors set a goal to get a genome sequence for every Psilocybe type specimen. To date, they’ve generated genomes of 71 type specimens and continue to collaborate with collections around the world.

“It’s impossible to overstate the importance of collections for doing studies like this. We are standing on the shoulders of giants, who spent thousands of people-power hours to create these collections, so that I can write an email and request access to rare specimens, many of which have only ever been collected once, and may never be collected again,” said Bradshaw.

Other authors who contributed to the study include Ali Awan of Guy’s and St. Thomas’ NHS Trust, Giuliana Furci of the Fungi Foundation, and Laura Guzmán-Dávalos of the Universidad de Guadalajara. The research was funded by the National Science Foundation (DEB #2114785) and Fungi Perfecti LLC.

Monday, February 26, 2024

 

Poison center calls for ‘magic mushrooms’ spiked after decriminalization, study finds


Tripled for adolescents, doubled for young adults between 2018-2022


Peer-Reviewed Publication

UNIVERSITY OF VIRGINIA HEALTH SYSTEM

Christopher Holstege, MD 

IMAGE: 

CHRISTOPHER HOLSTEGE, MD, CO-AUTHORED A STUDY THAT FOUND CALLS TO U.S. POISON CENTERS INVOLVING “MAGIC MUSHROOMS” AMONG ADOLESCENTS AND YOUNG ADULTS ROSE SHARPLY AFTER SEVERAL U.S. CITIES AND STATES BEGAN DECRIMINALIZING THE HALLUCINOGEN.

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CREDIT: UVA HEALTH




Calls to U.S. poison centers involving psilocybin, or “magic mushrooms,” among adolescents and young adults rose sharply after several U.S. cities and states began decriminalizing the hallucinogen, University of Virginia School of Medicine researchers have found. 

Psilocybin-related calls more than tripled among teens ages 13-19 from 152 to 464 and more than doubled among adults ages 20-25 from 125 to 294 between 2018 and 2022, according to anonymized data gathered from the National Poison Data System. Local and state efforts to decriminalize the possession, use and cultivation of psilocybin began in May 2019. Oregon and Colorado have decriminalized psilocybin, as have several cities, including Washington, D.C., Detroit and Seattle.

By comparison, the number of psilocybin-related calls to poison centers for patients ages 13-25 was largely unchanged between 2013 and 2018, the researchers found.

“It is markedly concerning to me that children are gaining access to these products,” said Christopher Holstege, MD, director of UVA Health’s Blue Ridge Poison Center and chief of the Division of Medical Toxicology at the UVA School of Medicine. “We have limited data on the potential long-term consequences on the developing brains of children when exposed to such compounds that impact the brain’s neurotransmission. We also do not understand fully why some individuals have markedly adverse complications to psilocybin, known as ‘bad trips,’ that can lead to harm to the individual taking or others who may be victims of violent behavior.”

Psilocybin’s Effects

During the 10 years examined in the study, most calls involved intentional consumption of psilocybin (81.1% of calls for ages 13-19 and 78.3% of calls for ages 20-25). Males accounted for about 75% of the calls in both age groups.

Approximately 75% of the youths ages 13-19 and 72% of the young adults required some type of medical attention after being exposed solely to psilocybin. The researchers found that the most common effects of the drug were hallucinations or delusions (36.6% of calls), agitation (27.6%), abnormally fast heart rate (20.2%) and confusion (16%). The powerful psychological effects of psilocybin can, even in moderate doses, cause adverse reactions that can include anxiety, disorientation, fear, grief, paranoia and panic attacks. Psilocybin-induced impairments in judgment and perception can contribute to dangerous behavior, accidents, self-harming and even a risk of suicide. There are reports of deaths from falls or jumps from tall buildings attributed to psilocybin use.  

The researchers note that the increase in psilocybin-related calls among young people from 2018-2022 is “particularly alarming” because the hallucinogen’s use is banned for those ages 21 and younger even in cities and states where it has been decriminalized.

“As psilocybin may become more widely available, it is important for parents to be aware that psilocybin is also available in edible forms such as chocolate and gummies,” said Rita Farah, PharmD, MPH, PhD, the Blue Ridge Poison Center epidemiologist. “And we learned from our experience with edible cannabis that young children can mistake edibles for candy.”

If someone has an adverse reaction to psilocybin or any other substance, trained healthcare providers at the Blue Ridge Poison Center are available to help around the clock. Call 800.222.1222 for assistance. Calls are free and confidential.

Findings Published

The researchers have published their findings in the Journal of Adolescent Health. The research team included Farah, Abigail Kerns, Austin Murray, and Holstege. 

Thursday, November 03, 2022

Psychedelic Treatment with Psilocybin Relieves Major Depression, Study Shows

11/04/2020

Note: To view and download footage of Roland Griffiths, Ph.D., talking about his research, click here. To view and download footage of a research participant talking about his experience in Johns Hopkins' psilocybin study, click here.

In a small study of adults with major depression, Johns Hopkins Medicine researchers report that two doses of the psychedelic substance psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms, with most participants showing improvement and half of study participants achieving remission through the four-week follow-up.