Mind Medicine has presented positive topline data in Basel, Switzerland in April from a double-blind, investigator-initiated trial evaluating lysergide (LSD) in the treatment of Major Depressive Disorder (MDD).
Professor Matthias Liechti and Dr Felix Mueller, MindMed collaborators at University Hospital Basel (UHB) and the University Hospital of Psychiatry, released the data, which demonstrated significant, rapid, durable and beneficial effects of LSD and its potential to mitigate symptoms of MDD.
The high dose LSD regimen saw patients receive 100 µg at their first dosing day and 200 µg at their second dosing day (separated by four weeks).
Mind Med has stated that the results saw statistically and clinically significant improvements on the primary endpoint, which was the change in clinician-rated Inventory of Depressive Symptomatology (IDS-C) scores six weeks after the first administration as compared to control (whether or not the patient received a second administration).
The control group in this study received a lower dose regimen of 25 µg on both treatment days.
According to the company, the patients in the high dose arm demonstrated a least-square mean change from baseline in IDS-C scores of -12.9 points compared to -3.6 points in the lower dose arm. The statistically significant benefit as measured by IDS-C was maintained up to 16 weeks after the first administration compared to placebo.
Data from the secondary endpoints were also encouraging. The investigational drug was generally well-tolerated, as indicated by reported adverse events, changes in vital signs and laboratory values.
CEO and Director of MindMed, Robert Barrow, stated: “We continue to be encouraged by the positive results being generated on the clinical activity of lysergide by our collaborators at UHB.
“The statistically and clinically significant improvements observed in this study reinforce preliminary findings that have shown the clinical potential of lysergide in anxiety, depression and other brain health disorders. These positive findings are particularly relevant to our MM-120 program in generalised anxiety disorder [GAD], given the high degree of comorbidity of GAD and MDD.
“I would like to congratulate and thank our collaborators at UHB for once again generating high quality clinical data that continue to support the progression of our pipeline.”
Professor Liechti, co-primary investigator of the trial, commented: “Historical studies of lysergide in MDD demonstrated rapid, robust and sustained improvement in depressive symptoms.
“We also observed improvement in depressive symptoms in patients with anxiety disorders in another of our recently published trials. We believed it was necessary to confirm the historical studies with ones using modern methods.
“Hence, we designed this randomised-controlled trial to assess the benefits of lysergide treatment in MDD. Importantly, an active small dose of lysergide was used as the control.
“We are extremely encouraged by the results we presented today, which demonstrate the strong, rapid and enduring improvements of this compound in patients suffering from MDD. We look forward to publishing the completed results in a peer-reviewed journal along with additional analyses. Our lab will continue investigating the therapeutic potential of lysergide and other psychedelics.”
Mapping the effects of ketamine on the brain
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.
Psilocybin analogue shows positive results in Phase 2 depression study
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.
Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research
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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- Psychedelic therapy programmes launch to address heartbreak, burnout and more
- Psilocybin analogue shows positive results in Phase 2 depression study
- Ketamine: understanding the K-Hole
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- Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research
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