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Exploring psychedelics for the treatment of dementia

Return Health is investigating the efficacy of psychedelic derivatives for halting the progression of the devastating condition.



Exploring psychedelics for the treatment of dementia

Return Health is exploring psychedelic derivatives for the treatment of dementia. CEO, James Kuo, MD, spoke to Psychedelic Health about the company’s aims and its use of Artificial Intelligence for finding the best treatment candidate.

Biotech company Return Health is developing novel, non-hallucinogenic psychedelic derivatives to alter the progression of dementia. It is aiming to develop treatments that can reduce behavioural and psychological symptoms associated with the disease, and reverse cognitive decline.

According to the World Health Organisation (WHO), there are more than 55 million people living with dementia across the globe, with nearly 10 million new cases every year. Alzheimer’s causes around 50 per cent of all dementia, and there are currently no effective FDA-approved treatments for the disease.

“Dementia is perhaps the largest unsolved medical problem out there today, and we have partly ignored it and just let it continue,” says Kuo. “We are applying psychedelics toward treating dementia. 

See also  Could psychedelics combat the cognitive decline of dementia? 

“We have broken down the problem into two components. The first one is the behavioural and psychological symptoms of dementia – which is the emotional and personality changes that occur. Sometimes they are the first indicator that someone has dementia, including symptoms such as anxiety, agitation, depression and apathy.

“We believe that psychedelics have already been shown in existing clinical trials to have efficacy there. So, we think we should be able to demonstrate that psychedelics are effective in treating those symptoms.”

Studies into psychedelics, such as DMT, have demonstrated that the compounds increase neural plasticity – an effect that could be beneficial in the treatment of dementia.

“There is also the cognitive decline aspect. We are targeting three mechanisms there. The first is neuroplasticity – which is rewiring the brain. In dementia, typically, the problem is with the prefrontal cortex or the hippocampus which is responsible for memory. So, if the brain is damaged, the best thing to do is to rewire the brain. So, we are focused on doing that as one mechanism. 

“The second mechanism is regrowing nerve cells. That is an aspect that is not so familiar to people, but it is called neurogenesis and drugs like Prozac are capable of doing that. We are applying psychedelics for neurogenesis. 

“The third one is reducing neural inflammation. There is a lot of inflammation, damage by the immune system, to the brain associated with Alzheimer’s, and reducing that would be tremendously helpful.”

Return Health is currently searching for the best new chemical entity that could help the disease by looking at tryptamine compound structures – the chemical backbone of psychedelics.

“We are not just targeting one serotonin receptor and 5-HT2A – the main receptor that most people focus on for the psychedelic effects – but there are other serotonin receptors that we think are very important for neurogenesis and for reducing neural inflammation.

“Most likely it is going to be something similar to DMT, because DMT has been the compound that, in animal studies, has been shown to be the best for neurogenesis and for cognitive decline. We believe we will do that within a year, then we will be ready for clinical studies with that compound.”

Return Health will be using Artificial Intelligence (AI)-assisted drug discovery to identify new psychedelic derivatives that have the effect they are looking for, but which will not have hallucinogenic properties.

“The way it is traditionally done within a pharmaceutical company is that you take chemical structures and make a lot of derivatives called a chemical library. And that can be thousands of them. You then put them through an assay, using what is called an in vitro assay, to see if there is any effect. That is a very expensive, laborious and time-consuming process.

“The new technology that has been rolling out throughout the pharmaceutical industry is utilising AI where this process is all done on a computer. You can do the vast majority of drug screening and then when you get to the shortlist of ideal candidates, you can synthesise them and test them in the in vitro assays in animal models. This way you can compress the lengthy, multi-year process into a relatively shorter time period,” says Kuo.

“There is actually several receptors that we want our ideal candidate to touch – some very lightly and other receptors we wanted to avoid completely. So, it is a case of programming the algorithm into the computer and then letting the computer go through the known universe of all the tryptamine structures out there – everything that has been in the public domain – and ranking each candidate chemical structure for its affinity for binding to the serotonin receptors we want to touch.”

Dementia is currently the seventh leading cause of death, and healthcare costs associated with the disease reach USD$817bn globally. Kuo says finding a treatment for the disease could lift a huge burden on health and social care for the disease, and bring hope to millions of families across the globe.

“Dementia destroys the lives of patients and impairs their brain function. They cannot live independently – simple things such as going out in your car to the store – you cannot figure your way home you get lost, or you forget to turn the stove off when you start cooking. Things like that can be very dangerous and obviously, highly impair someone.

“There is also the caregiver component – the disease is very devastating for the families having to care for a patient, and that is really one of the things that we are targeting. If we can target the behavioural and psychological symptoms of dementia, it would be much more effective to have someone take a pill than to have them be under supervised medical care. This would lead to tremendous cost savings. Perhaps this could be the one pill that saves more money in the healthcare system than anything else. 

“The very interesting thing about psychedelics is that they appear to work on the worst patients, the patients who have failed everything else. Most drug developers do not like to go in that area because they feel it puts an undue burden on candidate drugs. If a patient is very sick, they may die of many causes that are not related to the drug, but if they die, then they’ll be attributed to the drug. Psychedelics are just the opposite. For example, in treatment-resistant depression, by definition, these patients have failed multiple therapies for their depression. Psychedelics seem to work better in that condition, and they also work for a longer duration of time after just one or two, possibly even three doses – sometimes for up to six months. So, they are really quite remarkable. 

“There has been really no innovation in CNS [central nervous system] care for 33 years. That is a long period of time for very little to happen. The last innovation was really when Prozac was launched, and there were other similar drugs that followed. But, while they provided some relief for some patients, the vast majority were not helped by them. They have terrible side effects, like sexual dysfunction, which is probably the main reason why people do not take SSRIs.

“Psychedelics have a very colourful, interesting story because they were around before and they were very promising but then the government weighed in and restricted them – stopping all research. They are now coming back to life again after several decades of dormancy, and it is very exciting. There is a history of their use for thousands of years for spiritual and medicinal reasons, by shamans, for example. So, we are very excited to be working in this area and developing drugs for patients and their families who desperately need them.”

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Integrating metaphysics into psychedelic therapy



Integrating metaphysics into psychedelic therapy

Dr Peter Sjöstedt-Hughes, Lecturer at Exeter University, has proposed incorporating metaphysical philosophy into psychedelic therapy to help improve therapeutic outcomes.

Sjöstedt-Hughes suggests that psychedelic therapy may gain more advantage by extending its scope into metaphysics, helping patients better integrate and understand psychedelic-induced metaphysical experiences.

Such improved outcomes may be seen if patients undergoing this therapy “are provided with an optional, additional, and intelligible schema and discussion of metaphysical options at the integrative phase of the therapy.” 

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In the paper, Sjöstedt-Hughes puts forward this schema as the “Metaphysics Matrix” and an accompanying “Metaphysics Matrix Questionnaire (MMQ)” which can be utilised by therapists and researchers as a tool for the quantitative measurement of a psychedelic experience.

The paper ‘On the need for metaphysics in psychedelic therapy and research’ has been published in Frontiers in Psychology.

What is metaphysics?

While mysticism deals with understanding the universe through direct experience, such as revelation, metaphysics is a branch of philosophy that deals with understanding the fundamental nature of reality through logic/argument.

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Sjöstedt-Hughes writes that “metaphysics is not mysticism” but there is overlap: “[…] metaphysics is broader and its positions can be logically deliberated — as such metaphysics can encompass mystical experiences induced by psychedelic intake yet metaphysics can also ground those experiences in a manner that can be more intelligible, comprehensive, viable, and acceptable to participants than that which the framework of mysticism alone can offer.”  

The Metaphysics Matrix

A number of clinical trials investigating psychedelic-assisted psychotherapy for the treatment of mental health conditions, such as anxiety and depression, report that participants who undergo a “mystical experience” during a psychedelic session often have higher levels of sustained therapeutic outcomes.

In clinical trials, mystical experiences are measured by different scales including the Mystical Experience Questionnaire (MEQ), the Hood Mysticism Scale (HMS), the Hallucinogen Rating Scale (HRS), the Five Dimensions Altered State of Consciousness Questionnaires (5D-ASC) and Eleven Dimensions Altered State of Consciousness Questionnaires (11D-ASC).

Sjöstedt-Hughes writes: “Data derived in this manner is obviously limited and abstract not only because psychedelic experience need not be “mystical,” but also because the definition of “mystical” could be expanded to include other criteria [

“With regard to psychedelic-assisted psychotherapy […] speaking about mystical experience per se will not be sufficient to provide a meaningful explanation of the significance of such experience to a person, for the simple reason that mystical experience is the phenomenon to be explained — mystical experience is the explanandum rather than the explanation. 

“It is metaphysics that is the means of explanation, the explanans of the mystical explanandum.”

The Metaphysics Matrix has been designed to provide a “menu” of metaphysical options that may help people to “frame, make sense of, and give significance to, their experiences”, and would be another tool in the belt of therapists to better understand these experiences.

Image provided by Dr Peter Sjöstedt-Hughes.

Such experiences could be understood through metaphysical systems such as Neutral Monism, Pantheism, Panpsychism, Animism, Substance Dualism, and Idealism, says Sjöstedt-Hughes. 

Some examples provided include the common experience of the Universe being God – which can be understood in the context of Pantheism – or of all matter having a basic form of sentience – such as plants having a basic drive or process – which can be understood in the context of Panpsychism. 

Image provided by Dr Peter Sjöstedt-Hughes.

Additionally, enabling people who have had these experiences to understand them within these frameworks may make them less likely to dismiss the experiences as delusional, says Sjöstedt-Hughes.

“ […] Relatedly, that the worldview hitherto adopted by the participant is but one metaphysical position amongst others,” he writes. 

Sjöstedt-Hughes commented: “This is a conjecture that hasn’t been tested but can be tested – offering a patient an additional and optional discussion in the integrative phase of psychedelic-assisted psychotherapy. 

“Giving them this Metaphysics Menu for integration may extend the long-term benefits of psychedelic therapy and beyond because there’s a number of studies that seem to show that certain peak psychedelic experiences have the longest and most beneficial health outputs results.

“If in the integrative phase [of therapy] one looks at that experience and starts to frame it intelligibly, then the conjecture is that the participant will not in a few weeks after that, think it must have been a delusion – they will say that we don’t know what reality is. 

“Therefore, we can’t dismiss something as a delusion necessarily. By doing that it might extend the significance of that experience for the person.

“When we use Mysticism Scales, by definition, mystery can’t explain itself. Metaphysics, however, incorporates those experiences and offers an explanation to what they mean. For example, the relation between oneself and the universe.”

Sjöstedt-Hughes points out that in practice, one of the immediate issues is the practical issue of implementation of Metaphysics Integration, suggesting this could be supported through resources such as a handbook or practitioner training.

He further concludes the integration would need to be “further bridged by the therapist to the participant’s life, concerns, values, aims, and outlook.”

The Metaphysics Schema is already being utilised in studies taking place at Ohio State University, US, and Exeter University, UK.

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Ketamine nasal spray for anxiety and PTSD advances



Cybin to acquire Small Pharma, creating largest DMT programme

Silo Pharma has announced it has advanced the formulation development for its therapeutic drug, SPC-15, which utilises ketamine.

The liquid nasal formulation will be used in SPC-15’s novel protocol that aims to treat and prevent anxiety, post-traumatic stress disorder (PTSD), and other stress-related disorders. 

Chief Executive Officer of Silo Pharma, Eric Weisblum, stated: “The progress of our feasibility study investigating dose strengths of SPC-15 is a significant advancement in our development work with this pipeline candidate.

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“Results of the feasibility study will determine our selection of the manufacturing processes, and we are currently in discussions with potential delivery partners.

“We may also use the feasibility data for upcoming studies related to our SPC-14 therapeutic targeting Alzheimer’s disease.”

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The company has stated that the formulation development was in accordance with its sponsored research agreement and option with Columbia University, and that linearity, accuracy, and repeatability were achieved in the feasibility study.

In May 2023, Silo Pharma was awarded a U.S. Patent titled “Biomarkers for Efficacy of Prophylactic Treatments Against Stress-Induced Affective Disorders,” with claims protecting the key technology behind SPC-15 and further drug discovery.

The company is also carrying out a Sponsored Research Agreement with the University of California, San Francisco (UCSF) – Effect of Psilocybin on Inflammation in the Blood – which is investigating psilocybin’s effect on inflammatory activity in humans, with plans to accelerate its implementation as a potential treatment for Parkinson’s, chronic pain and bipolar disorder.

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How psychedelics could help those living with alcohol use disorders



Psychedelic retreats are mushrooming

Alcohol use disorders (AUD) are estimated to affect around 237 million people across the globe, with 3 million deaths each year attributed to the harmful use of alcohol.

Despite this prevalence, there is a lack of effective treatment options and relapse rates remain high, but hope is on the horizon in the form of clinical research that is starting to show the therapeutic potential of psychedelic compounds for problematic drinking.

AUD affects millions of people around the world. In fact, approximately one in every 20 deaths globally are in some way related to alcohol, be it through disease, injury, or accident. There are over 600,000 dependent drinkers in England alone, and, in the US, roughly a third of people meet the criteria for AUD on a lifetime basis. Sadly though, only 21.9% of patients across the globe receive treatment for AUD and many struggle with relapse. 

Why is this? Well, put simply, the treatment landscape for AUD is incredibly complex and there are many barriers throughout the treatment pipeline. Whether it’s the mental barrier of actually wanting to stop drinking, physical dependence, fear of withdrawal symptoms, the lack of awareness of what support is actually available, or the cost of treatment, it can be difficult for people living with AUD to know what to do.  

And even if they are screened by a healthcare professional, the treatments available may not be effective for them. There may be undesired side effects and up to 70% of people taking pharmacological treatments for AUD find no positive outcomes. This means there is a huge unmet need for better, more effective and more accessible treatments – and this is where psychedelics come in. 

How psychedelics are offering hope to those that struggle most

Thanks to a growing body of research, psychedelics have become a new medicine of interest for those looking to ease the burden substance use disorders have on individuals, families and healthcare systems. Psychedelics are believed to work by inducing a ‘window of neuroplasticity’ in the brain, which opens up the possibility for new behaviours or patterns of thinking to be developed. It is this ability that makes psychedelics so interesting in the case of treating conditions like AUD where addiction-related habits and emotions play a huge part.

The science is promising. In the U.S, a recent study led by the New York University Grossman School of Medicine showed that psilocybin treatment improved drinking outcomes in patients with AUD relative to outcomes observed with a placebo medication. Specifically, the study found that two doses of psilocybin, when combined with psychotherapy, reduced heavy drinking by 83%. Another study found that ibogaine, a psychedelic derived from the roots of a West African shrub, when used in conjunction with psychotherapy, could increase periods of abstinence in those with alcohol and other substance addictions. 

At Beckley Psytech, we’re exploring the potential of our synthetic formulation of 5-MeO-DMT, BPL-003, for AUD in a Phase IIa study. Phase I healthy volunteer data has already shown that BPL-003 is well-tolerated and can reliably induce profound subjective experiences (a correlate of positive clinical outcomes) with a rapid onset and timely offset of perceptual effects. The Phase IIa study will explore the safety, efficacy and pharmacokinetics of BPL-003 alongside an abstinence-oriented cognitive behavioural programme in patients diagnosed with AUD. Topline results are expected later this year.

Collaboration is critical

It is, of course, still early days but the science seems to be indicating that psychedelics, when administered in the right context and with the right support, can help those who are suffering from a range of mental health conditions. With clinical studies progressing, and approval for other psychedelic treatments expected in the next few years, now is the time to develop the infrastructure that will allow us to actually deliver these interventions to people living with AUD. This involves us all: patients, regulators, investors, healthcare professionals and drug developers.

At Beckley Psytech, we are always looking to hear from others in the space so please head over to to learn more about our work in AUD and how to get in touch.

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