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What do recent ketamine findings mean for depression treatment?

Psychiatrist Dr Tiago Reis Marques says that new research findings on ketamine’s mechanism of action could allow us to produce more, and eventually better antidepressants.

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Awakn to bring ketamine-assisted therapy for AUD to the US

Psychiatrist Dr Tiago Reis Marques discusses what new research findings on ketamine mean for treatment-resistant mental conditions such as major depressive disorder.

Ketamine is currently administered intravenously in clinical settings as a fast-acting antidepressant for treatment-resistant depression. Recent findings from researchers at Karolinska Institutet in Sweden uncovered the mechanisms behind ketamine’s antidepressant effects, demonstrating that ketamine directly stimulates AMPA receptors – part of the nerve cell that receives signals – leading to the increased release of adenosine (a neurotransmitter) which inhibits presynaptic glutamate release.

The researchers said the findings are new knowledge that can explain some of the rapid effects of the medicine and suggest that the “antidepressant action of ketamine can be regulated by a feedback mechanism.”

See also  New findings on how ketamine prevents depression raise treatment hope

Dr Tiago Reis Marques, psychiatrist and researcher with over 15 years of experience studying and treating psychiatric disorders, and CEO of Pasithea Therapeutics, which has ketamine clinics in the UK and Us to treat depression and post-traumatic stress disorder (PTSD), explains why these new findings provide hope for new treatment options for major depressive disorder in the future.

“It is a very interesting study because our understanding of how ketamine works from its basic action has been that ketamine works on the NMDA receptor which is a glutamatergic receptor, so, there is basically a rapid release of a neurotransmitter called glutamate.  

“This is why everyone thought that ketamine is a fast-acting antidepressant, it increases the levels of glutamate in the brain. This was a bit contradictory as the literature shows that in patients with depression, there was already an increase of glutamate levels. The question now was that, if patients already have an increase in glutamate levels, how can a drug that further increases this have an antidepressant property?

“Then research progressed which showed that ketamine also works on a receptor called AMPA, which is also a glutamatergic receptor. Research shows that blockage of the AMPA receptor was fundamental for ketamine’s antidepressant properties. 

See also  Ketamine and esketamine show no adverse cognitive effects

“What this new study shows is that, when ketamine blocks the AMPA receptor, it actually induced an increase of substance called adenosine which is a neurotransmitter – which then binds to adenosine receptors. There’s two types of adenosine receptor – A1 and A2. In this case, when it binds to the A1 receptor it causes a reduction in glutamate levels. So, basically, ketamine can bind to two glutamatergic receptors.

“Therefore, what the study shows is that ketamine has a complex mechanism of action with region-specific changes on glutamate levels in the brain.”

Dr Marques says the animal study is well designed, but that, as it is hard to conduct this type of experiment in humans, and because of the complexity of human psychiatric disorders, the findings need to be extrapolated from the animal study.

“As the study was done in rodents – in terms of its regional actions on the brain – a rat brain is very different from the human brain, but that is something that will be further explored in future studies. 

“The findings of this study will not change the way that ketamine is administered. But, they show the action through the AMPA receptor and that the A1 receptor is also involved. So, if we are trying to find future antidepressant drugs we might not look to other NMDA blockers but instead look for drugs that act on AMPA or on the downstream A1 receptor.

“By elucidating a method of action, it will allow us to produce more, and eventually better antidepressants and possibly, without the negative aspects of ketamine – such as the side effects and the potential for abuse. We are always trying to produce drugs with more efficacy and fewer side effects and we can only do that when we understand how these how drugs work, and what the mechanisms are that are involved in depression. So, the next step for this research will be to try to relate these findings into a human antidepressant effect.”

Marques highlights that the efficacy of ketamine treatment in patients with treatment-resistant depression is between 50 to 70 per cent.

“It is not a miracle drug but it is definitely a revolution in terms of having a new drug as a treatment for depression, as it has a completely different mechanism of action to other antidepressants. The study is another piece of the puzzle for what seems to be a very complex drug.”

What do recent ketamine findings mean for depression treatment?

Dr Marques, CEO at Pasithea

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Evegreen

How the Medical Psychedelics Working Group is Moving the Needle on UK Drug Policy

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One of Britain’s central think tanks for drug policy reform is looking for new partners to join forces in 2026.

Over its five-year history, the group has achieved major milestones, which include consulting with the UK Home Office on a recent call for submissions on barriers to research scheduled substances.

In July 2025 the UK government responded to recommendations by the Advisory Council on the Misuse of Drugs on rescheduling psychedelics for clinical research, agreeing in principle to ease licensing for universities and hospitals and exempt approved clinical trials from Home Office licences.

“I like to think we swayed them with our evidence”, said James Bunn, Head of Operations at Drug Science, the organisation overseeing the group.

The group is currently on the lookout for new members and corporate partners.

“We’ve seen what collaboration can achieve with medical cannabis. Now it’s time to apply that same evidence-based, patient-led approach to psychedelics”, said Drug Science founder Professor David Nutt. 

What Is the Medical Psychedelics Working Group?

The Medical Psychedelics Working Group was established in 2020 in response to growing scientific evidence, shifting regulatory landscapes, and the persistent barriers facing legitimate psychedelic research. 

Following the legalisation of medical cannabis in the UK in 2018, a need emerged for coordinated, interdisciplinary action to ensure psychedelic medicines could be responsibly developed within public health systems.

Created to challenge decades of medical marginalisation, the group seeks to advance a rational and evidence-based approach to psychedelic research and clinical treatment. Its work focuses on generating robust scientific data, supporting regulatory reform, and improving understanding among policymakers, clinicians, researchers, and the wider public. 

Central to this mission is addressing the constraints imposed by Schedule 1 classification, which continues to limit research through cost, complexity, and delay.

“While the legislation did not preclude scientific research with these drugs, it made them significantly more difficult, time-consuming and costly to study”, said Bunn. “Drug Science’s Medical Psychedelics Working Group aims to change this situation for the better.”

Major Achievements and Upcoming Goals

Currently, the group is running an MDMA psychotherapy research trial in collaboration with University College London. The study aims to improve understanding of MDMA-assisted psychotherapy, focusing on how the psychotherapeutic component interacts with the drug’s effects. The project aims to clarify treatment mechanisms and enhance safety and efficacy.

Drug Science Head of Research, Dr. Anne Schlag, says the group is “continuously responding to the government’s call for evidence”.

This includes a recent response to a 2026 ketamine review by the Advisory Council on the Misuse of Drugs, which was commissioned last year to assess harms and legal classification. 

With funding by Norrsken Foundation, the group is running an MCDA (multi-criteria decision analysis) comparing treatments for treatment resistant depression, including psilocybin and ketamine. We can expect results for the analysis before July, says Schlag.

The group is also working closely together with Australian colleagues such as Prof Ranil Gunewardene, to understand, document and publish everything related to the developments in MDMA and psilocybin rescheduling in Australia.

“We hope [it] can serve as an example for the UK and Europe. A very exciting case series of the first fifteen MDMA patients is forthcoming!” says Schlag.

Other key achievements include developing the ARC: a framework for Access, Reciprocity and Conduct in psychedelic therapies, which was published in Frontiers in Psychiatry in 2023; and developing a lexicon for psychedelic research and treatment, described as “a key paper delineating a standardised terminology for clinical development and regulatory classification for psychedelic medicines.”

An upcoming project focused on psilocybin for palliative care will be announced over the summer.

“I would urge any organisation that shares our vision to join us in shaping the future of mental healthcare”, concludes Prof. Nutt.

Illustration made using AI tools.

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Can Psilocybin Be Safe and Effective for Anorexia? Shortwave Life Sciences Is Leading a Study To Find Out

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Psilocybin continues to gain momentum as a possible alternative to mental health treatments that leave large numbers of patients without recovery. 

Shortwave Life Sciences is a company that’s currently working on a feasibility study to prove whether psilocybin can be delivered safely, accepted by patients and integrated smoothly into clinical practice, for the treatment of anorexia.

The company presented its most recent findings at the latest edition of PSYCH Symposium 2025, in a panel called “Designing Breakthroughs: A New Human Study for Anorexia Treatment,” led by Chief Medical Advisor Dr. Nadya Lisovoder.

Psilocybin for Anorexia: An Integrated Perspective

According to Lisovoder, anorexia nervosa carries the highest mortality of all psychiatric disorders, driven by both medical complications and suicide.

In an interview, Lisovoder told Psychedelic Health that “the illness itself is exceptionally complex” because “it is a multifactorial condition that involves emotional, cognitive and physiological mechanisms at the same time.”

For that reason, not much therapeutic innovation has been seen in trying to combat the condition since developing a single medicine that can influence all of these layers has been extremely difficult.

“Most traditional treatments focus on one pathway only. In anorexia, that is rarely enough. The psychological patterns, the fear circuits, the rigid thinking styles and the metabolic consequences all reinforce each other. Treating just one aspect does not shift the illness in a meaningful way,” says Lisovoder.

That has led Shortwave to develop an integrated perspective. 

“Our approach aims to engage several relevant receptor systems and neural pathways simultaneously, addressing the mental and emotional dimensions of anorexia in a more complete way,” she told us.

By doing so, Shortwave aims to create conditions that can also support improvement in the underlying physiology, because in this illness the mental state and the physical state are deeply interconnected.

Scientific evidence may support Shortwave’s thesis. A systematic review published in the British Medical Journal in 2024 found that psilocybin could be as effective as escitalopram, a selective serotonin reuptake inhibitor (SSRI), in treating depressive symptoms.

“Psilocybin is considered a promising candidate for conditions defined by rigid cognition and compulsive patterns because it can temporarily soften the fixed neural networks that shape these behaviours,” said Lisovoder.

Research also shows that it creates an increase in neuroplasticity, allowing the brain to form new associations and to respond more flexibly to emotional and environmental cues. In disorders where people become locked into narrow patterns of thought or behaviour, like anorexia, this short period of increased adaptability may provide a meaningful therapeutic opportunity.

These same principles are relevant to anorexia nervosa, where inflexible thinking, heightened fear responses and avoidance-driven routines play a central role.

“Even a modest shift in these underlying circuits can support change when combined with the right clinical framework,” says Lisovoder.

A Unique Formulation 

Shortwave’s plan is to build on the known effects of psilocybin but not rely on it alone. Its formulation includes an additional component intended to influence complementary pathways, reflecting the company’s view that complex psychiatric and neurological conditions are best approached through more than one mechanism.

To administer the treatment, the company is developing a psilocybin-based buccal film designed specifically for patients with severe anorexia nervosa, addressing both biological and practical barriers to treatment.

Patients with anorexia can have their gastrointestinal function compromised. For this reason, Shortwave chose a method of administration that bypasses the gut altogether: a buccal film allows the active components to be absorbed by oral mucosa in the cheek and enter directly into the bloodstream. 

“Non-invasive, easy to administer format increases acceptability in a population that often avoids medications, procedures and anything perceived as forceful,” says Lisovoder. 

Shortwave’s Feasibility Study On Psilocybin for Anorexia

A safe and credible feasibility study in anorexia nervosa must begin with a clear focus on safety, Lisovoder says.

The first aim is to confirm that the treatment can be given without harm, with careful monitoring and a responsible medical framework. Because anorexia involves both medical fragility and deeply rooted cognitive and emotional behaviours, the protocol has to keep the burden on participants as low as possible, supported by a psychiatric and nutritional environment that understands the condition well.

Recruitment is often challenging in this field, which makes partnerships with established eating disorder centres essential. The company is in partnership with Sheba Medical Centre in Israel, whose eating disorders unit is recognised internationally for its clinical and research expertise, with a large and diverse patient population and a highly experienced psychiatric and medical team.

“Having an established collaboration with such a centre allows us to design studies with real clinical insight, consult with leading clinicians, and recruit participants more efficiently and responsibly,” said Lisovoder.

Lisovoder is hopeful for the treatment, beyond the results of the feasibility trial. She says there is a possibility that this line of research could help shift the way we think about eating disorders more broadly.

“For many years, these illnesses have been approached mainly through behavioural and psychological frameworks, which are important but do not fully reflect the underlying biology. The emerging science suggests that patterns of fear, avoidance, cognitive rigidity and altered reward processing all play a role, and that these patterns can be influenced at the neurocircuit level. If we can show that targeted modulation of these circuits contributes to meaningful change, it may open the door to a more integrated model of care,” she told us.

Such a shift would not replace psychological treatment, but rather add a biological dimension that has been missing, concludes Lisovoder

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Is Ketamine Therapy Only Reaching The Wealthy? Dr. Celia Morgan On Expanding Equitable Access

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Dr. Celia Morgan is one of the UK’s leading figures in ketamine and psychedelic research, especially in the domain of addiction and mental health.

Based at the University of Exeter, she holds the Chair of Psychopharmacology and leads trials exploring how ketamine, paired with psychotherapy, can break cycles of relapse in substance misuse.

Morgan has led some of the largest clinical trials on ketamine-assisted therapy for alcohol use disorder and will be speaking at the upcoming PSYCH Symposium: London 2025, to be held at Conway Hall on December 4.

“I think that the most promising findings from our work with ketamine are of the sense of agency and autonomy in their recovery that the people we are working with experience,” she told Psychedelic Health in a written interview.

Still, she thinks several key challenges need to be tackled for these treatments to be able to reach more people. One of the biggest of such challenges is ensuring equitable access to these treatments.

“We see a relatively homogenous and privileged group in most studies, our work has tried to address this,” she said.

Building the infrastructure to safely deliver these treatments in public healthcare systems is another big challenge for the industry, she said.

Yet the healthcare sector can also take advantage of Ketamine’s regulated status to allow for a faster roll-out, when compared to other psychedelics like MDMA or psilocybin.

“Some of the recent recommendations by the Royal College fo Psychiatrists are steps on the way towards more widespread use,” she said.

What distinguishes Morgan in the psychedelics field is her dual commitment. She studies the risks and harms of recreational ketamine use while simultaneously designing controlled, clinical applications for it.

One of her flagship projects is Exeter’s KARE trial (Ketamine for Reduction of Alcohol Relapse), which blends ketamine infusions with psychotherapy for patients with alcohol use disorder. Early published data show dramatic improvements in abstinence rates during six-month follow-ups, far exceeding baseline relapse rates. Morgan has also worked on trials for gambling disorder and other behavioral addictions, expanding the frontier of what ketamine-assisted therapy might treat.

Morgan also plays a role in academia’s response to the psychedelic renaissance, she’s a co-lead on Exeter’s postgraduate certificate in psychedelic studies, a program designed to train clinicians, researchers, and therapists in the science and ethics of psychedelic medicine.

“I think its important to keep on with our efforts to study, regulate and roll out these treatments principally for the patients who might benefit from psychedelics as I have seen first hand in my work,” she said.

Picture is extracted from an interview with Dr. Morgan at PSYCH Symposium’s 2022 edition.

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Psychedelic Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. We do not provide medical advice or promote the personal use of psychedelic compounds. Please seek professional medical advice if you are concerned about any of the issues raised.

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