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DMT study shows improvement in depression and anxiety symptoms

Small Pharma, which carried out the study, suggests the results show DMT’s potential as a treatment in indications beyond depression.



DMT study shows improvement in depression and anxiety symptoms

Small Pharma has announced results from its Phase 2a trial of its intravenous formulation of DMT – SPL026 – demonstrating improvement in depression and anxiety. 

The study is the first placebo-controlled study of a short-duration psychedelic for the treatment of Major Depressive Disorder (MDD). 

The trial investigated the efficacy and safety of a 21.5mg dose of SPL026 with supportive therapy in 34 patients with moderate to severe MDD. 

Analyses of additional secondary and exploratory endpoints, including effects on self-reported depression, anxiety and wellbeing, demonstrated that patients receiving at least a single dose of IV SPL026 with supportive therapy experienced clinically relevant improvements in function and mood.

See also  DMT for major depression trial shows promising results

The company states that this supports previously announced topline efficacy results.

Chief Medical and Scientific Officer, Dr Carol Routledge, commented: “We are encouraged by the data from our additional analyses, which further strengthens our previously reported topline efficacy results. 

“We are pleased that patient reported outcomes on depression symptoms and broader measures on wellbeing are reflective of the rapid and durable antidepressant effects demonstrated by independent rater assessment using MADRS [Montgomery-Asberg Depression Rating Scale]. 

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“Importantly, the data suggests that SPL026 has the potential to offer symptom relief from elevated anxiety, providing an encouraging basis from which to further explore its potential as a treatment for anxiety-related disorders. 

“This data will help inform our future clinical strategy as we think about the expansion of the SPL026 clinical programme and broader pipeline.”

The study

In January 2023, Small Pharma reported that the Phase 2a trial met its primary endpoint with a statistically significant and clinically relevant reduction in depression symptoms at two-weeks post-dose, compared to placebo. 

SPL026 with supportive therapy also demonstrated a rapid onset and durable antidepressant effect, as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).

Small Pharma has said that the analysis of patient-reported depression scores corroborate the MADRS assessments conducted by independent clinical raters. 

Improvements in depression scores from baseline were observed across all study timepoints in patients receiving at least a single dose of SPL026, as measured by the Beck Depression Inventory (BDI), including a statistically significant improvement in depression symptoms compared to placebo at two-weeks post-dose. 

The efficacy outcomes on the BDI were consistent with MADRS, providing additional support for the rapid and sustained therapeutic profile of SPL026 for the treatment of MDD.

Measures assessing patients’ anxiety and wellbeing were also analysed across the study. 

Following both one and two doses of IV SPL026 with supportive therapy, patients demonstrated a rapid and sustained improvement in anxiety symptoms as measured by the State-Trait Anxiety Inventory-Trait (STAI-T) scale. 

A statistically significant improvement in anxiety symptoms was observed compared to placebo at two-weeks post-dose. 

At 12-weeks following the open-label dose, a -14.2 mean change from baseline (CFB) was demonstrated in the patient group receiving the single dose regimen.

Further, a rapid and sustained improvement in wellbeing was observed following at least a single treatment of IV SPL026 with supportive therapy, as measured by the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). 

The results at two-weeks following the blinded dose of SPL026 or placebo showed a 10.1 mean CFB in the SPL026 group compared to 0.9 in the placebo group.

Statistical analysis was conducted on the MADRS open-label data. A statistically significant difference in mean total MADRS score was observed for both the one and two dose regimen groups across all open-label study timepoints. 

Further analysis was conducted to assess the difference in total MADRS scores between the one and two dose regimen groups using a mixed model of repeated measures for all subjects across all timepoints. 

No statistical difference was demonstrated between these dose regimens across all time points to 12 weeks. This analysis provides further support that a single dose of SPL026 is sufficient to elicit a rapid and durable antidepressant effect.

Further analysis of the Phase 2a dataset is ongoing and full trial results will be submitted for publication in a peer-reviewed journal.

CEO, George Tziras, said: “Alongside our recent release of positive topline efficacy results from the Phase IIa study, this additional analysis demonstrates that a single treatment of SPL026 with therapy has the potential to lead not only to rapid and long-lasting relief from depression but provide improvements in anxiety symptoms and offer a broader benefit to patients’ wellbeing. 

“With an estimated cost of USD$1 trillion in lost global economic productivity due to depression, the potential for a treatment to offer a more holistic improvement in patients’ mental health has the potential to reduce negative societal and economic impacts of MDD.”

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Mapping the effects of ketamine on the brain



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.

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Psilocybin analogue shows positive results in Phase 2 depression study



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.

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Clerkenwell Health calls for volunteers to support groundbreaking psychedelic research



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.

See also  Clerkenwell Health is launching a free UK psychedelic therapist training programme

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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