Research
Groundbreaking psilocybin study results show promise for depression

Published
2 years agoon

The largest psilocybin therapy clinical trial ever conducted, investigating psilocybin for treatment-resistant depression (TRD), has achieved its primary endpoint.
COMPASS Pathways has announced that its randomised, controlled, double-blind phase IIb trial of psilocybin therapy for TRD has achieved its primary endpoint for the highest dose. A 25mg dose of the compound – COMP360 – demonstrated a highly statistically significant and clinically relevant reduction in depressive symptom severity after three weeks, with rapid and durable treatment response.
The objective of the trial was to find the appropriate dose for a larger, pivotal phase III programme, which COMPASS expects to begin in 2022.
David J Hellerstein MD, commented: “Treatment-resistant depression is a common and devastating condition, affecting tens of millions of people, with few effective treatments. This is the largest modern study of a psychedelic drug, combined with psychological support, enrolling over 200 people with TRD.
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“In this groundbreaking study, a single dose of psilocybin, given in conjunction with psychological support, generated a rapid response that lasted up to 12 weeks. Remission rates appear to be higher than seen in traditional medication studies.
“We now have evidence from a large well-designed trial that psilocybin may be effective for people with treatment-resistant major depressive disorder. These findings suggest that COMP360 psilocybin therapy could play a major role in psychiatric care, if approved.”
In the trial, all patients discontinued antidepressants prior to participation, and the trial was powered to compare two active doses of COMP360, 25mg and 10mg, against a comparator 1mg dose.
The 25mg group versus the 1mg group showed a -6.6 difference on the Montgomery-Asberg Depression Rating Scale (MADRS) depression scale at week three, and the 25mg group demonstrated statistical significance on the MADRS efficacy endpoint on the day after the COMP360 psilocybin administration. The 10mg vs 1mg dose did not show a statistically significant difference at week three.
COMPASS said that at least twice the number of patients in the 25mg group showed response and remission at week three and week 12, compared with the 1mg group: “The protocol-defined sustained response up to week 12 was double, with 20.3 per cent of patients in the 25mg group vs 10.1 per cent in the 1mg group. Using a definition of sustained response that is consistent with other TRD studies, the difference was more than double, with 24.1 per cent of patients in the 25mg group vs 10.1 per cent in the 1mg group.”
CEO and co-founder, of COMPASS, George Goldsmith, said: “No one is untouched by the mental health crisis – everyone has a story. We urgently need options for people who are not helped by existing therapies. We set out to explore the safety and efficacy of COMP360 psilocybin therapy in treatment-resistant depression, through a rigorous and large-scale trial, and to find an appropriate dose to take to the next stage.
“I am delighted that we have succeeded in doing this. We have demonstrated our ability to execute an innovative, multicentre, multinational clinical trial programme – and in the midst of a global pandemic.
“Our work follows the efforts and achievements of so many researchers before us, and we are grateful to all of them and for the opportunity to work with the mental health care community to transform patient experience and patient outcomes.
“With our world-leading psychedelic research over the last few years, we have now created a unique and extensive data lake; this provides an unprecedented opportunity to further evaluate and optimise psilocybin therapy for patients suffering with serious mental health illness. With these compelling data, we will urgently progress our clinical development programme and move closer to making this therapy accessible to patients in need, if approved.”
The company added that COMP360 was generally well tolerated, with more than 90 per cent of treatment-emergent adverse events (TEAE) being mild or moderate in severity. 179 patients reported at least one TEAE; the most common TEAEs across treatment groups were headache, nausea, fatigue and insomnia.
There were 12 patients who reported treatment-emergent serious adverse events (TESAEs). These TESAEs included suicidal behaviour, intentional self-injury, and suicidal ideation, which are regularly observed in a treatment-resistant depression patient population, and which occurred more frequently in the 25mg group than in the 10mg or 1 mg groups. Overall, 209 patients completed the study; there were five withdrawals from the 25mg group, nine from the 10mg, and 10 from the 1mg.
Robin Carhart-Harris PhD, Director of the Psychedelics Division at the Weill Institute for Neurosciences at the University of California San Francisco, and Ralph Metzner Distinguished Professor of Neurology, Psychiatry and Behavioral Sciences, said: “This is an important and exciting moment for the mental health care community.
“It builds upon more than two decades of research into the viability of psychedelic compounds to treat mental health conditions and demonstrates the potential it has in helping people living with treatment-resistant depression. It’s encouraging to see how far this field has progressed in the last 20 years and I look forward to further research.”
COMPASS is conducting comprehensive secondary analyses which are expected to further inform the clinical development programme for COMP360 psilocybin therapy.
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Research
Mapping the effects of ketamine on the brain

Published
3 days agoon
5th December 2023By
News Editor
A new study has mapped the effects of ketamine on the brain, finding that repeated use over extended periods creates widespread structural changes in the brain’s dopamine system.
The study found that repeated ketamine exposure leads to a decrease in dopamine neurons in midbrain regions linked to regulating mood. They also revealed an increase in dopamine neurons in the hypothalamus, which regulates the body’s basic functions like metabolism and homeostasis.
A former finding that ketamine decreases dopamine in the midbrain, may indicate why long-term abuse of ketamine could cause users to exhibit similar symptoms to people with schizophrenia.
The researchers suggest that their new finding that ketamine increases dopamine in the parts of the brain that regulate metabolism, published in Cell Reports, may help explain why it shows promise in treating eating disorders.
They suggest this strengthens the case for developing ketamine therapies that target specific areas of the brain, rather than administering doses that wash the entire brain in ketamine.
Raju Tomer, the senior author of the paper, stated: “Instead of bathing the entire brain in ketamine, as most therapies now do, our whole-brain mapping data indicates that a safer approach would be to target specific parts of the brain with it, so as to minimise unintended effects on other dopamine regions of the brain.”
Tracking detailed data
The researchers tracked highly detailed data that enabled them to track how ketamine affects dopamine networks across the brain.
The insight revealed that ketamine reduced the density of dopamine axons (nerve fibers) in the areas of the brain responsible for hearing and vision, while increasing dopamine axons in the brain’s cognitive centers, which may help explain the dissociative behavioral effects observed in individuals exposed to ketamine.
Malika Datta, a co-author of the paper, added: “The restructuring of the brain’s dopamine system that we see after repeated ketamine use may be linked to cognitive behavioral changes over time.”
Most studies of ketamine’s effects on the brain to-date have looked at the effects of acute exposure – how one dose affects the brain in the immediate term.
For this study, researchers examined repeated daily exposure over the course of up to ten days. Statistically significant alterations to the brain’s dopamine makeup were only measurably detectable after ten days of daily ketamine use.
The researchers also assessed the effects of repeated exposure to the drug at two doses, one dose analogous to the dose used to model depression treatment in mice, and another closer to the dose that induces anesthesia. The drug’s effects on dopamine system were visible at both doses.
“The study is charting a new technological frontier in how to conduct high-resolution studies of the entire brain,” said Yannan Chen, paper co-author.
It is the first successful attempt to map changes induced by chronic ketamine exposure at what is known as “sub-cellular resolution,” in other words, down to the level of seeing ketamine’s effects on parts of individual cells.
Most sub-cellular studies of ketamine’s effects conducted to date have been hypothesis-driven investigations of one area of the brain that researchers have targeted because they believed that it might play an important role in how the brain metabolises the drug.
This study is the first sub-cellular study to examine the entire brain without first forming such a hypothesis.
Bradley Miller, a Columbia psychiatrist and neuroscientist who focuses on depression, said: “Ketamine rapidly resolves depression in many patients with treatment-resistant depression, and it is being investigated for longer-term use to prevent the relapse of depression.
“This study reveals how ketamine rewires the brain with repeated use. This is an essential step for developing targeted treatments that effectively treat depression without some of the unwanted side effects of ketamine.”
“This study gives us a deeper brain-wide perspective of how ketamine functions that we hope will contribute to improved uses of this highly promising drug in various clinical settings as well as help minimise its recreational abuse. More broadly, the study demonstrates that the same type of neurons located in different brain regions can be affected differently by the same drug,” added Tomer.
Research
Psilocybin analogue shows positive results in Phase 2 depression study

Published
1 week agoon
30th November 2023By
News Editor
Cybin has announced positive Phase 2 topline safety and efficacy data for its proprietary deuterated psilocybin analogue – CYB003 – for the treatment of major depressive disorder (MDD).
Results from Cybin’s study have shown that 79% of patients were in remission from depression at six weeks after receiving two doses of CYB003.
CYB003 demonstrated a large improvement in symptoms after one dose and a total of 79% of patients were responsive to the treatment. The compound also demonstrated an excellent safety profile in doses tested, with all reported adverse events mild to moderate and self–limiting.
Additionally, Cybin has stated that the magnitude of improvement was superior compared to approved antidepressants and recently reported data with other psychedelics, stating that the effects translate into an unprecedented effect size.
The company has said that the results compare favorably to pooled data from 232 industry studies of current standard-of-care antidepressants, SSRIs, submitted to the FDA.
The announcement follows Phase 2 interim results in early November 2023, which demonstrated that CYB003 saw a “rapid, robust and statistically significant reduction in symptoms of depression three weeks following a single 12mg dose compared to placebo”.
Cybin CEO, Doug Drysdale, stated: “We are delighted to share that CYB003 achieved the primary efficacy endpoint in this study and showed rapid and statistically significant improvements in depression symptoms after a single dose, with a clear incremental benefit of a second dose, resulting in four out of five patients in remission from their depression at six weeks.
“This is an impressive finding and follows on from the unprecedented interim results we announced earlier this month.”
Drysdale emphasised that the strength of the data will support CYB003 into Phase 3 of the study.
Cybin CMO, Amir Inamdar, added: “The significant reduction in depression symptoms observed in our Phase 2 study is highly gratifying.
“At the three-week primary efficacy endpoint, a single 12mg dose of CYB003 showed a rapid, robust, and highly statistically significant improvement in depression symptoms compared to placebo, with a -14.08 point difference in change from baseline in MADRS.
“This translated into a very large effect size. Similar significant and robust effects were also seen with a single 16mg dose, which resulted in an improvement in symptoms of depression as measured using the MADRS total score by about 13 points versus placebo.
“These effects were evident on day one with the 16mg dose and were also highly statistically significant. When data from 12mg and 16mg are pooled, these robust effects are maintained. Further, with two doses, response and remission rates in excess of 75% were observed with CYB003 (12mg).
“With these findings in hand, we are encouraged by the potential of CYB003 to help those with MDD and look forward to progressing to a multinational, multisite Phase 3 study early next year.”
Cybin is planning on submitting topline data to the FDA with an aim to hold a Phase 2 meeting in Q1 of 2024, with further 12-week durability data from Phase 2 CYB003 expected in Q1, and recruitment for the Phase 3 study anticipated to begin by the end of Q1 2024.
Research
Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research

Published
2 weeks agoon
27th November 2023By
News Editor
Mental health research provider Clerkenwell Health is calling for volunteers to join its groundbreaking clinical trials that will research whether psychedelics can provide effective treatments for complex mental health conditions.
Clerkenwell is seeking a diverse group of volunteers from across the UK between 18 and 65 years old to take part in the trials if they suffer from a relevant condition.
The trials, which will be conducted at Clerkenwell Health’s purpose-built facility near Harley Street in London, are being run in partnership with a number of world-leading drug developers to test whether psychedelic drugs – often combined with talking therapy – can offer a new approach to treating a variety of mental health illnesses.
Clerkenwell Health is seeking volunteers for trials that look to find cures for a range of conditions, including PTSD, depression, alcohol use disorder and anorexia.
Many of the conditions have few successful treatment options and Clerkenwell’s innovative methods of combining psychedelics with therapy aim to to treat these problems more holistically, providing long-term quality of life for patients.
Chief Scientific Officer at Clerkenwell Health, Dr Henry Fisher, said: “With the current system for treating mental health disorders simply not working, we’re calling for patients to help identify the next wave of treatments.
“These have the potential to be groundbreaking for the millions of people across the UK who are affected by poor mental health.
“The status quo for mental health treatment has not only resulted in patients experiencing debilitating side-effects, huge waiting lists and high relapse rates, but is costly, complicated and broadly ineffective.
“By participating in upcoming clinical trials, patients have an opportunity to make a valuable contribution to growing research which will support the development of the next generation treatments for mental health conditions.”
According to MIND, approximately 1 in 4 people in the UK will be affected by a mental health condition each year and with a significant rise in people contacting mental health services in recent years, there has never been a more desperate need to identify new and innovative treatments.
Given the challenges facing the country’s health service and with mental health challenges on the rise, the search for volunteers to test effective treatments has never been more pressing.
Clerkenwell has stated, in this regard, that it has gone national with its search for volunteers in an effort to deliver medical breakthroughs in mental health akin to the Polio clinical trials in the 20th Century.
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