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PSYCH NEWS – 18/02/26

david-blackbourn

By David Blackbourn

shutterstock 2214552825
in this article
  • DMT and Major Depressive Disorder
  • Psilocybin Phase III Trials
  • Is the “Trip” the Point?
  • Ketamine for Suicidality
  • The Harm-Benefit Analysis
  • Ketamine and Chronic Fatigue
  • Clinical Trial Reform in the UK
david-blackbourn

By David Blackbourn

Disclaimer: The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Chemical Collective or any associated parties.

DMT and Major Depressive Disorder

A landmark study published in Nature Medicine on 16th February looks like it might have finally cracked the biggest problem in psychedelic therapy. Researchers from Imperial College London teamed up with Helus, the firm created when Small Pharma and Cybin merged, to release results from their Phase IIa trial on SPL026. This is essentially a proprietary version of synthetic DMT, specifically tested on people suffering from moderate to severe major depressive disorder.

This trial is a massive departure from what we usually see with psilocybin or LSD. Those older models require a patient to be in a clinic for six to eight hours, which in practice would be a total logistical nightmare for an overstretched NHS. Compass Pathways’ COMP360 psilocybin trial is currently underway with this exact methodology. The DMT protocol utilising SPL026, however, lasts just twenty-five minutes. For anyone tracking this industry, this is definitely a current search at the forefront – finding a molecule that gives you the powerful neuroplastic effects, but fits into a standard outpatient appointment scenario. This is, of course, very challenging.

The study involved 34 participants with a mean age of 32.8 years, most of whom had been struggling with depression for over a decade. Each person got a single 21.5 milligram dose of intravenous DMT fumarate, given as a ten-minute infusion with proper psychological support. The results were pretty clear. There “was…an average 7.4-point reduction in MADRS from baseline,” with the DMT group showing a mean difference of -7.35 points compared to the placebo group.

What really stands out is how fast this works. The antidepressant effects were apparent after just one week. By the two-week mark, remission rates were at 29% for the DMT group, compared to just 12% for the placebo group. Even better, the effects actually stuck around. During the open-label phase, these benefits lasted up to three months, and some people stayed in recovery for half a year. Dr David Erritzoe, the lead investigator, pointed out that a single DMT session can be safe, effective, and durable while taking up a fraction of the time.

The potential for scaling this within public health systems is huge. If a patient can get through a whole session in under half an hour, the cost of keeping therapists and monitors in the room drops dramatically. It completely negates the time/economic argument that has held psilocybin back, where the sheer costs of paying multiple therapists for eight hours outweigh the medical benefits – especially when expanded to more than individual cases.

The study also looked at the experience itself. It turns out that the people who had the most intense acute experiences usually saw the biggest clinical improvements. Interestingly, there was no real difference between getting one dose or two. It suggests that one high-quality, supported session might be all you need for long-term benefit. This pretty much kills the idea that you need constant dosing to stay well, as long as that first experience is powerful enough. As a final aside, this also somewhat throws a bit of a spanner in the works as to the potential efficacy of the increasingly popular “microdosing” method of dosing.

Psilocybin Phase III Trials

While DMT is currently making headlines for its incredible rapidity, psilocybin is still very much the leading substance currently being investigated. On 17th February, Compass Pathways announced they had hit the primary endpoint in their massive COMP006 Phase III trial. They were testing COMP360, their own synthetic psilocybin, on people with treatment-resistant depression (TRD). With 581 participants across North America and Europe, this is easily one of the biggest and most serious studies we have ever seen in this space.

Because the results were so good, Compass has already asked for a meeting with the FDA to talk about a rolling submission for a New Drug Application. They are looking to have that all wrapped up by the end of the year. This is a massive deal. We are now looking at a very real timeline in which psilocybin could be a legal, prescribable medicine in the West by 2027. As stated in the previous story in relation to COMP360, however, the issue will lie perhaps less in the efficacy of the substance itself, but rather in our ability to scale it so it is accessible.

The trial confirmed that “COMP360 25 mg versus 1 mg demonstrated a highly statistically significant and clinically meaningful reduction in symptom severity as measured by MADRS”.

Just like with the previous DMT study, changes occurred very quickly. People saw improvements the very next day after their first dose, and those gains stuck around through the entire six-week period.

The durability data looks promising, too. About 39% of the people in the 25 milligram group saw a real difference at six weeks, and for those who responded, the benefits lasted all the way to the 26-week mark. Safety is always the big question with these compounds because of the old stigmas, but Compass reported that most side effects, like headaches or nausea, were mild and mostly gone within around 24 hours.

The study found that “across both Phase 3 trials to date, COMP360 [demonstrated] a generally well-tolerated and safe profile with no unexpected safety findings.” There is also “no evidence of a clinically meaningful imbalance between treatment arms in suicidality in either study”.

That is a vital stat when you are dealing with a group as vulnerable as those with TRD. Kabir Nath, Chief Executive Officer at Compass Pathways, said:

Across three robust, well-designed and well-executed clinical trials involving more than 1,000 participants, we have now demonstrated consistent, highly statistically significant results at the primary endpoint and a clinically meaningful effect. This is a remarkable achievement for the field of psychiatry – especially in the TRD population, where proving benefit has historically been extraordinarily challenging.

Guy Goodwin, MD, Chief Medical Officer of Compass Pathways, explains the importance of the study as a whole:

“TRD patients have extremely limited treatment options, and the unmet need remains profound. The promising clinical profile of COMP360 reinforces our belief in its potential to set a new standard of care for this population.”

COMP360 has a very unique profile. For patients who have tried every pill on the market and failed, a treatment that only requires one or two doses is a total paradigm shift. Compass Pathways is now focusing on the final regulatory hurdles and the practical side of things, like training enough therapists and figuring out how to fit this into the existing psychiatric system.

Is the “Trip” the Point?

One of the longest-running arguments in psychedelic science is whether the “trip” is actually a necessary part of the healing process or just a side effect of the drug doing its thing in the brain. A new analysis of the KARE trial, published in the journal Addiction, has demonstrated some strong evidence suggesting it might be the latter. Researchers from King’s College London and the University of Exeter followed 96 adults with moderate to severe alcohol use disorder to see if the intensity of their psychoactive experience actually predicted how well they stayed sober.

The participants went through three weekly infusions of ketamine alongside their therapy. Some of the patients had some typical ketamine side-effects, ranging from full out-of-body experiences to total perceptual distortions, but the researchers found what amounts to zero proof that the intensity of those feelings actually made the treatment any more effective. When they looked at how many days someone abstained from alcohol over a six-month period, it had very little to do with how hard they were tripping during the sessions.

Dr Will Lawn, who led the study at King’s, noted that while ketamine obviously triggers some strong psychedelic effects, the real therapeutic benefits might be driven by other mechanisms entirely.

We are likely talking about things like neuroplasticity, growing new neural connections, and rewiring the reward circuits that addiction tends to hijack. This is of huge interest for the biotech firms currently trying to develop non-hallucinogenic psychedelics. If you can get the brain-healing benefits without the mind-bending hallucinations, the whole regulatory and clinical process becomes a lot easier to deal with. Whether this kind of thing holds true for substances like psilocybin or LSD is still a bit of a question mark, though, as the psychological breakthrough is usually seen as the whole point of those therapies.

Indeed, several studies have found that some key aspects of the experience predict therapeutic outcomes, such as intensity of effects, mystical experiences, emotional breakthroughs, and psychological insight. Even challenging experiences can often lead to beneficial effects for people if they are sources of insight, wisdom, and personal growth.

The debate really highlights a kind of fundamental split in the field. You have one side arguing that the psychedelic state allows for a cognitive reframing of trauma that a simple chemical fix just cannot match. Then you have the other side suggesting the trip is just what happens when certain receptors get flooded, while the real heavy lifting happens at the synaptic level. For alcohol use disorder, at least, it looks like the physical rewiring of the brain might be the bit that actually matters.

Ketamine for Suicidality

Whether or not the “trip” itself matters, the practical side of using ketamine for people in crisis is progressing fast. On 17th February, NRx Pharmaceuticals announced they had a successful sit-down with the FDA about NRX-100. NRX-100 is a proprietary version of ketamine, which is administered intravenously. It looks like the FDA has now given them a clear green light for a New Drug Application to treat treatment-resistant depression when acute suicidality is involved.

In what is a massive shift in how things are regulated, the FDA agreed that NRx can use “Real World Evidence” from a database of over 65,000 patients to back up their trial data. This dataset, which they put together with Osmind (a network of over 800 independent psychiatry practices), covers nearly a million treatment sessions and is easily one of the most detailed looks we have at how ketamine is actually being used in the real world. The numbers from NRx were pretty striking: they saw a 55% response rate in suicidal patients, compared to just 30% in the control group. Even better, about 63% of patients saw their suicidal ideation vanish in just three days.

The FDA reassured them that they will not need any additional non-clinical studies for this specific formulation. That sounds like a boring technicality, but it’s actually quite a big deal because older versions of ketamine often have benzethonium chloride in them, which can be a bit of a problem in high doses. NRx is now aiming for a broad approval that would cover not just people in immediate danger, but the whole range of TRD patients who deal with suicidality.

This development is a huge step for high-risk groups, like veterans or first responders, who really need something that kicks in way faster than your typical antidepressants. The company is planning to get its application in by the second quarter of 2026, hoping for a final decision before the year is out. The fact that the FDA is starting to accept this kind of real-world evidence suggests they are perhaps becoming a bit more pragmatic, acknowledging that the last decade of clinical use gives us a mountain of data that traditional, individual trials just can’t really match.

The Harm-Benefit Analysis

On 28th January, the Advisory Council on the Misuse of Drugs (ACMD) put out an updated assessment of the harms of ketamine, which serves as a sobering reminder of the risks involved when the drug is used outside of a clinic. This review was largely prompted by a surge in recreational use among younger people in the UK, which has led to a corresponding rise in some pretty severe health complications.

The report was particularly worried about ketamine cystitis, a condition where the drug’s metabolites essentially shred the lining of the bladder and urinary tract. In people who use high doses chronically, this can lead to permanent scarring and a total loss of bladder capacity, sometimes even requiring life-altering surgery to remove the bladder entirely. The council also noted more cases of liver and bile duct injuries, as well as the kind of neurocognitive decline you often see with frequent use.

Despite these risks, the ACMD actually recommended that ketamine should “remain a class B controlled substance, but that police forces and health care professionals must receive greater support to better identify, prevent and respond to ketamine‑related harms.”

They argued that bumping it up to Class A wouldn’t really do much to stop people from using it, and it would likely just increase the stigma that keeps people from seeking medical help for their bladder issues. The ACMD Chair Professor David Wood said in relation to the report, “The ACMD report highlights the need for a ‘whole system approach’ through its recommendations to tackle issues related to ketamine use, as no single recommendation is sufficient to do this alone.”

A “whole system approach” basically means coordinated action across the health service, the police, and schools.

Crucially for the research community, the report also recommended that the government should reduce the barriers that make it so hard to do legitimate clinical research into psychedelics. This highlights a bit of a balancing act for the people making the rules: trying to reduce the very real harms of illicit, high-dose misuse while still making it easier to develop the drug as a breakthrough psychiatric medicine in controlled clinical settings. This split between medical benefit and recreational harm is quickly becoming a central theme of the current era – especially due to the prevalence of outdated ideas at the top.

Ketamine and Chronic Fatigue

In yet more ketamine related news, a small study from mid-February has been looking into whether ketamine could actually help treat chronic fatigue. This was led by a team at Rutgers Health and the NIH. They took ten people who were dealing with the soul-crushing exhaustion you can struggle with, with conditions like fibromyalgia or lupus. The logic behind it is actually quite straightforward: fatigue levels often seem to track with glutamate receptor concentrations in the blood (glutamate is a neurotransmitter which is essential for brain function, learning, and memory). Since ketamine is a heavy-duty glutamate blocker, the researchers surmised it may be able to provide some sort of reset.

The results were positive, meeting the threshold they set out with. Fatigue scores dropped by about 21% three days after just one low-dose infusion. If you look at the 24-hour mark, it was even better, with a 39% decrease. But – and there is always a catch – ketamine didn’t actually do much better than the “active placebo”, which was midazolam. That drug also seemed to help with fatigue in the short term. So, while ketamine definitely gives you a quick energy boost, we’re going to need much bigger studies to see if it’s actually better than just a standard sedative.

The study’s senior author, Professor Leorey Saligan, explains that even a temporary bump in energy could be enough to let patients actually engage with things like exercise or physical rehab, which we already know provide more of a long-term fix.

“The idea is to prompt or reset the brain so people feel more motivated and able to take part in treatments that are proven to reduce fatigue.”

Even though this was a tiny study, it suggests that the anti-fatigue side of these molecules is worth a much closer look. For conditions like ME/CFS, which have been mostly ignored or dismissed by the medical world for decades, the idea of a neurological reset could be life-changing. It opens up a whole new way of looking at a condition that is notoriously difficult to treat and, frankly, often just brushed under the carpet in clinical settings.

Clinical Trial Reform in the UK

We’re finally seeing what looks like the most massive structural shift in the UK’s research landscape in over twenty years. The MHRA has just confirmed that a huge set of reforms for clinical trial rules is due to kick in on 28th April. The whole point of these changes is to dramatically lessen the red tape holding back potential therapies and make sure the UK stays a top-tier global hub for innovations like psychedelic therapies.

The big headline figure here is that they want to get the time from a trial application to the first patient walking through the door down to just 150 days. To actually make that happen, the MHRA is bringing in a 14-day limit for assessing Phase I trials. They are also starting up a “fast-track” notification route for lower-risk studies. This means that about 20% of trials could get automatic approval if they tick the right boxes, which skips months of back-and-forth with the (let’s face it, often ill-informed) bureaucrats.

Crucially, these reforms are finally introducing a single, combined review process for both the MHRA and the ethics committees. For psychedelic researchers, who usually have to jump through an extra set of hoops because of the controlled status of the drugs, this is going to be a massive relief. The new rules are moving away from the one-size-fits-all approach and instead allow for more flexible, risk-based oversight. That’s a big deal for trials that involve really intensive psychological support or novel new ways of giving the drug.

There is also a heavy focus on being more transparent. Every trial now has to be registered in a public list before it even starts, and they have to publish a summary of the results within a year of completion. The government’s goal is clear: they want to pull in international investment by creating a predictable and agile environment. If the UK can prove it is the fastest place on Earth to get a psychedelic trial off the ground, we could potentially see a number of biotech firms moving their operations over to British soil.

David Blackbourn | Community Blogger at Chemical Collective

David is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Sam via email at samwoolfe@gmail.com

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