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The music of psychedelics

Dr. Mendel Kaelen doesn’t believe the perfect playlist for psychedelic therapy exists. After ten years of research, Dr. Kaelen, Founder and CEO of Wavepaths, has developed an evidence-based, person-centered generative music product that allows the user and therapist to create a tailored music experience.

Wavepaths provides music both for and as psychedelic therapy, Mendel explained to the OPEN Foundation: “Music is a very powerful tool and I’m confident that we can view music as a psychedelic.”

He has understood this as a result of his experiences at Imperial College in London, where he worked as a PhD and postdoctoral neuroscientist, studying music’s role in psychedelic therapy.

“Psychedelics act as an agent that can reveal deeper parts of our being deeper parts of ourselves,” he explains, “and thereby can facilitate experiences that are meaningful and potentially life-changing.”

That’s revolutionary, he says: “Psychedelic therapy research is hinting at a new paradigm of understanding mental health: that the most effective way to facilitate change is by providing an experience. Not an idea, not a conversation but a directly felt fully embodied experience.”

“I’m talking about music in itself. So what we’re seeing already right now in our community is we have psychotherapists right now organically that joined our platform that are doing psychotherapy without psychedelic drugs. They are using Waveparts as an adjunct to deepen a particular experience.”

At ICPR 2022, Dr. Kaelen will shed light on the central role of music in psychedelic therapy, and hold a presentation titled The essential role of music in Psychedelic Therapy: 10 years of research.

A few last spots are still available for his workshop “Music For/As Psychedelic Therapy”, held on Wednesday September 21. Find out more at Mendel’s workshop page on the ICPR website.

psychedelic clinical trial participants share their stories

Story by Vardit Kohn
Illustration by Anna Temczuk

Until recently, there was no advocacy or central voice for the participants in clinical trials involving psychedelics. Now, there is PsyPAN, a non-profit organisation set up to connect and empower psychedelic participants. Founders Ian Roullier and Leonie Schneider both participated in such trials. Ian took part in the psilocybin for depression trials at Imperial College (2015) and Compass Pathways (2019). Leonie took part in the second phase of the psilocybin for depression study at Imperial College (2019) and the DMT for depression trial at Small Pharma (2022). They were later invited to take part in Dr. Rosalind Watts’ one-year integration programme, where they met.

Towards the end of the programme, Leonie and Ian discovered they had a shared interest – both in advocating for the spread of psychedelic treatment for mental health as well as having the patients’ perspective duly represented. No organisation representing the patient’s viewpoints existed, while the number of participants in psychedelic trials is increasing by the day. And as the standards for these novel treatments are now being developed, both felt that the voice of the patient needed to be heard louder.

So, in 2021, Leonie and Ian founded the Psychedelic Participant Advocacy Network: PsyPAN. It’s a non-profit organisation set up to connect and empower all psychedelic participants. PsyPAN aims to give a collective voice to all participants and help improve participant safety and wellbeing, by working on developing best practices across all levels of the global psychedelic sector – clinical and non-clinical alike. 

As the psychedelic sector is expanding at a breathtaking pace, companies, clinicians and modern-day curanderos alike have a lot to learn from the persons seeking their help. We talked to Leonie and Ian for this interview.

Leonie and Ian will also be speaking at ICPR 2022, the psychedelic conference organised by the OPEN Foundation, which has been promoting psychedelic research and therapy since 2007.

What motivated you to set up PsyPAN?
Ian: We both participated in clinical trials designed to test the effects of psilocybin and DMT on depression.  Our wildly varied, but generally positive personal experiences triggered a wish to bring these treatments to more people and at the same time ensure the treatments are delivered safely and responsibly. 

Leonie: We want to ensure the ‘participant’s voice’ is taken into account when clinical trials are designed, so that the trials can be tailored to meet the wide range of experiences. Despite some unifying themes across the psychedelic experience,, it is such a personal process, and deep trauma and psychological issues can present in so many different ways.  We want to provide a feedback loop: taking what participants say, giving that to industry, and having industry respond to what participants require in this process. So that we can ensure these treatments are tailored and take nuances and details into account.

Ian: Next to the ‘participants’ voice’ we keenly engage in advocacy work, destigmatizing the image of psychedelics, dispelling misunderstandings and fear. We are keen to ensure that more people can benefit from these treatments in a safe and appropriate way. 

Ian Roullier and Leonie Schneider recently launched the Psychedelic Participant Advocacy Network – PsyPAN. With their new organisation, they want to represent the voice of the participants of psychedelic trials. In this video, we go over some of the highlights of our conversation.

Is psychedelic therapy especially prone to safety risks?
Ian: Yes, psychedelic therapy is more risky than, for example, giving someone an SSRI. Psychedelic substances lay you bare and much more vulnerable, you can’t just get up and go back to work as if nothing happened. It is also their strength; but therein also lies the potential for healing. 

Leonie: Safety is therefore key, so developing psychedelic safeguarding guidelines is where we can help organisations.

Where do you see your contribution to the rapidly developing market of psychedelic therapy?
Ian: We work with organisations to ensure that they have the finer details in place, and we hope to develop a model of best practice that organisations could follow. 

Leonie: Sometimes there are issues organisations simply haven’t thought of because those involved haven’t suffered from the issues that people with a clinical diagnosis have gone through, nor have they taken part in clinical trials, so our feedback is valuable. We aim to help ensure that trials or treatments are delivered safely and appropriately, because the more corners cut, the less effective the treatment will be. 

What have you learned so far in the process that you were not expecting?
Ian: We found out that simply connecting people who have been through similar experiences is in itself of vital importance.

Leonie: Yeah. There is no community, or a place where you can go, to land after your experience. So it can be incredibly isolating. If you’ve been through a profound experience but can’t speak to anyone about it, you may still feel as isolated as you did pre-treatment, only in a different way. The circle of family and friends you go back to can’t necessarily understand what you have been through. We learned that there is a lot of value in simply creating a peer community for support.

Ian Rouillier and Leonie Schneider, featured in this article, will share their full stories at ICPR 2022, organised by the OPEN Foundation and held in Haarlem from 22-24 September 2022. Get €100 off on all tickets by using the code OPENBLOG100

If there was one thing you as participants in clinical trials would like to draw attention to, what would it be?
Ian : Open-label trials, in other words making sure that all participants who go through the process have access to a treatment dose. Contributing to science is wonderful, but if you’re so desperate as to be willing to participate in a clinical trial of a new substance, you really are in need of relief. To go through the process and only have a placebo is quite heartbreaking and potentially re-traumatising. To have access to the full treatment dose could therefore be life-saving for some. 

Leonie: Integration. Both of us participated in Rosalind Watts’ “Connectedness” program at Synthesis Institute which was the precursor to Dr Watts’ ACER Integration Programme, which was hugely beneficial. It connected us in monthly group meetings and group work (two groups of 10 participants each) for one full year. The psychedelics are catalysts, they likely allow more progress to be made during the integration. But this kind of deep, long-term integration and connection work has been hugely beneficial. 

Tell me more about Integration
Leonie: Having a space in which to integrate these experiences brought about by psychedelics is incredibly important, whether one-on-one or in a group, especially if the person has had long-term mental health issues. There is a need for longer-term and deeper level integration, not just a courtesy call of ‘how are you’. It’s about witnessing and supporting people every step of the journey.

As mentioned, we both participated in Rosalind Watts’ 1-year long “Connectedness” program. Due to Covid-19, the whole program was delivered online, which wasn’t the plan at all! And still it was so valuable. It kept many of us afloat, especially considering the pandemic. As long as there is a safe container, an online program can genuinely work.

The sweet spot could be to have online content enhanced with in-person meetings, hopefully in smaller, local groups (as treatments become more common) and outdoors, which allows for engagement with Nature. 

What part did the connection with Nature play in your healing process?
Leonie: Reconnecting with Nature and with every living thing is very powerful. For example, watching the same tree go through its year-long cycle, especially during the dark, deathly-looking winter months, realising this period is part of a longer cycle, realizing there is still a lot happening under the surface even if above ground the tree looks barren – this was all very meaningful. 

Most of mental illness is exacerbated by trying to avoid feelings as opposed to accepting them. When you learn to see low moods as “this is my Wintering, and Spring will come”, it creates a meaningful marker, a reference point. 

What should organisations emphasise as the most important factors for a patient to consider before deciding to join a clinical psychedelic study?
Leonie: Organisations running clinical trials must make potential participants aware that the ‘trip day’ is just a catalyst. You’re in the process for the long run and there will be plenty of long-term, steady work that only starts after the day at the clinic. The importance of long-term integration and connection after the ‘trip day’ cannot and should not be underestimated.

Ian: Expectations should also be carefully managed regarding the chances of getting into the trial. Many people aren’t accepted. Furthermore, organisations would do well to question the kind of support networks potential candidates have in place, because a lot of support is needed right from the recruitment and screening stages. What further support is available during and after the treatment? Is there a community and family in place that can hold your experience, so you do not end up in crushing isolation, which might negate any benefit you could get from the treatment?

Organisations engaging in double-blind trials should also make it very clear that participants have a 50-50 chance of getting a placebo, which may result in disappointment. In the case of depression, you need to come off the anti-depressant medication, which makes you more vulnerable. You hope for an improvement but may end up with a placebo, with all the disappointment and anxiety this may cause. You may potentially end up in a worse position than you were before entering the trial. 

To what extent if any does treatment with different psychedelic substances require different guidelines?
Leonie: It is certainly important to bear in mind what medicine you’re working with and then tailor the guidelines appropriately since the experiences vary in intensity, the type of in-session interaction and the kind of post-treatment support required depending on the medicine used. Furthermore, the theme of the session matters, too. As an example, if sexual issues are likely to arise, two therapists present and a recording of the sessions may provide more accountability.

How could the current positive hype around psychedelics impact patients and therapists?
Ian: There’s a risk in the current media hype for psychedelic therapy to be seen as a ‘one dose and you’re fixed forever’ treatment. It sets expectations too high, and, in the absence of legal treatments, people may opt to try the psychedelics themselves without appropriate support. 

Psychedelics are catalysts, not cures. In reality, when it comes to mental health a lot of the healing work happens afterwards.  It’s a long process that involves a lot of integration and support going forward. The focus should be more on the psychotherapy, not completely on the psychedelic aspect of the process. If this point isn’t made clear, the risk is that the treatments will be seen as ineffective, which would be a shame as there is huge potential in psychedelics.

How do participants’ opinions get heard through you?
Leonie: Participants who have been through the clinical trial setting are the ones most interested in our work, We raise awareness within organisations who run such trials and invite participants informally to join our efforts. Going forward, we want references to PsyPAN to be built into the treatment protocol so that participants can be seamly signposted to us and welcomes to participate if they choose to. 

Speaking at ICPR and other events where participants are present is another way of creating awareness of our work. We also help organisations put together a working or focus group, so participants can share their experiences and have a say in the way trial protocols are designed. 

Ian: As far as we know, there’s nobody doing exactly what we’re doing. If there are other such groups or networks, we will be delighted to connect with them and support each other. We’re all doing it for the greater good of people who are struggling with mental health conditions.

How do you view depression, as you were both treated for it.
Leonie: Depression is a disease of disconnection. In society we are disconnected in so many ways. Depression alerts us to a deep need to slow down, take deep rest and to reconnect: to Nature, to ourselves, to our feelings – all of them, including the painful ones. 

Ian: We live in a world where we’re atomized and isolated, and the pandemic only exacerbated that. We are raised to dismiss a large part of our emotional range as human beings. We try to deny the more challenging parts of ourselves and our histories. 

Leonie: Antidepressants are a powerful intervention when you are in an acute, overwhelming crisis. But they should be seen as a short-term, symptom management intervention. They should not be viewed as something that is taken indefinitely, as if depression was a terminal disease that you had to learn to live with, as they don’t just numb you to the negative emotions; they limit and numb you in many other ways, too. If you don’t deal with the underlying causes of your depression, the issues come up in a different way at a different time. 

Ian: Psychedelics work in the completely opposite way: they enable you to connect with your full range of emotions and learn to be comfortable with your fuller self. Psychedelics help you dig down to the roots of your depression and work out new ways to deal with difficult feelings within a natural container that is larger than just yourself. 

You mentioned several spiritual themes: connection to Nature, connection to something that is larger than us, the Cycle of Life. How does that sit with the current clinical, medical training?
Leonie: No participant or clinician starts the trial thinking clinically-diagnosed patients need more trees in their life… We must be careful not to be too reductionist – depression is not solely a function of neurochemistry. There needs to be some space for mystery, too. 

Ian: Psychedelics can engender deeply profound spiritual experiences, which can manifest in different ways; we must not be prescriptive as to the nature of the spiritual experience to be expected. Yet organisations who run the studies must be aware that these experiences do happen. 

Leonie: The concept of connectedness is a good place to start. Everyone can understand how being better connected to ourselves, each other and Nature is beneficial to all. It is definitely a point to bring to the discussion, otherwise we will be selling the psychedelic treatment short.

Hope or hype? Head of OPEN Foundation calls for caution in psychedelic renaissancE

Joost Breeksema is the director of the OPEN Foundation and one of the main initiators of the Interdisciplinary Conference on Psychedelic Research. ICPR 2022 will be held in Haarlem from 23-27 Sept

As the director of the OPEN Foundation – founded in 2006 to advance the scientific research of psychedelics – Joost Breeksema has usually found himself being one of the main promotors of psychiatric research into psychedelics and therapies. That has changed, he says:  “I find myself in a position of being somebody promoting more caution”.

“I think I still think that psychedelics have huge potential,” Breeksema says, “but I think it’s good to counterbalance this message a little bit and to have a proper balance between hype and hope.”

The OPEN director made his statement during the launch of PAREA, the Psychedelic Access And Research European Alliance, an association of European foundations and institutions advancing holistic and professional psychedelic research and therapy.

Breeksema commented in light of the recent psychedelic renaissance, which has brought renewed attention to the psychedelic field. Strong research results have shown the real efficacy of psychedelic therapy, but this has also spawned a world in which investment is luring, and potential risks of psychedelic therapy might be obscured. 

What the right balance is between hope and hype around psychedelic therapy, needs to be discussed, Breeksema says, because the need is dire: “There are many desperate patients out there. Between a quarter and a third of patients with mental disorders do not respond to conventional treatments. So there is a huge need for better and more effective treatments. But it’s also, I think, very important to remember that these are not magic bullets and there are interests.”

Professional field

The mix of patients with severe traumas and big expectations, the potential intenseness of the psychedelic experience, and the history of a black market involvement in the supply of many substances, make the need for safe, professional treatment a necessity: “When you ask patients… it’s hard work. People have challenging experiences, and these are vulnerable patients for the most part. These experiences can be powerful but also potentially destabilizing.” 

“These are not typical pharmaceutical drugs: It’s the experience that’s central, and that means people guiding patients through those experiences need to be properly trained. You need to be a mental health professional, but you do also need additional training.”

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The Pros and Cons of Psychedelic Self-Administration: A Conversation with Dr. Michiel van Elk

Should psychedelic researchers administer psychedelics to themselves? This has been an ongoing debate since psychedelics have been around. Michiel van Elk is a Dutch researcher who studies psychedelic, religious, spiritual and mystical experiences and has received a prestigious NWO (government) grant to study the effects of psychedelics. In a series with Jasper Lucas he discusses hot topics around psychedelic research.

Michiel van Elk, a professor of cognitive psychology at the University of Leiden, used to be very anti-drugs after growing up in a conservative Christian community. A psychedelic experience later in life put him on a path towards psychedelic research.

Van Elk now runs the PRiSM lab, which studies psychedelic, religious, spiritual, and mystical experiences, and has received a prestigious NWO (government) grant to study the effects of psychedelics. His previous work includes themes like religion, spirituality and altered states of consciousness, employing neuroscientific as well as cognitive and social psychology research methods. He is the author of the book ‘A sober look at psychedelics’ – available in Dutch – and will also speak at ICPR 2022.

Jasper Lucas is a Master’s student in Clinical and Health Psychology at the University of Leiden. He aims to pursue a career at the intersection of clinical research and practice, with a special interest in psychedelic-assisted psychotherapy. Jasper and Michiel recently had a wide-ranging discussion about issues surrounding the psychedelic science field.

Van Elk, at a certain point, was planning to develop a protocol which included the self-administration of psilocybin to test the feasibility of the experimental design – but this did not come to pass. This is part one of their conversation – about the self-administration of psychedelics. A topic that was long considered taboo, but is now facing new scrutiny. 

Jasper: First off, how did you get involved in researching psychedelics?

Michiel: I first came across psychedelics about five years ago during a sabbatical at Stanford University, where I met some highly motivated psychedelic researchers. Since then I’ve been involved in psychedelic research, initially focused on microdosing truffles. Right now I’m working on a bigger project on the influence of psilocybin on our brain, cognition, and perception, for which I was awarded a VIDI grant from the Dutch Association for Scientific Research (Stichting Nederlandse Wetenschappelijk Onderzoek Instituten, NWO). 

Jasper: A VIDI is one of the top government grants you can get as a researcher. What are the aims of your VIDI project?

Michiel: There are three parts to this project. The first is replication, focusing on the Relaxed Belief under Psychedelics (REBUS) model  – which has garnered much attention in recent years. There is some evidence in favor of it but there is a lot of discussion on how to specify the model, for example, which areas serve as lower and higher order areas and where exactly the predictions are implemented. Furthermore, there is the question of how exactly one should analyze fMRI data. Through open science practices like preregistration and many analysts’ approaches, we aim to see to what extent existing, general findings can be replicated. 

The second part concerns placebo effects. One perspective is that the effects of psychedelics are at least partially mediated by placebo effects because people have expectations about these effects. Another is that psychedelics are essentially super placebos by making people more suggestible, thereby enhancing the placebo response. 

Placebo research is an extensive, established field, which includes my own research with the God helmet. We aim to integrate this field of study with research into the psychedelic experience. How do expectations influence the psychedelic experience and how can psychedelics increase the placebo response?  

The third part is assessing the commonalities between different ways of inducing altered states of consciousness, including sensory deprivation, meditation and VR. We aim to assess to what extent these altered states are comparable to one another.

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Jasper: You have previously mentioned that, initially, you were thinking of beta-testing the protocol by going through the entire protocol yourself or by one of your PhD students, including the administration of psilocybin. You are no longer planning on doing so, but what type of insights would you have liked to gain from this self-administration, was it purely practical to assess feasibility or did you also expect some theoretical implications?

Michiel: It’s actually almost standard practice in experimental psychology and neuroscience to try out the experiment yourself first to see what the subjective experience is. You can really learn a lot from it. But, like you said, the most important reason to self-administer for this current protocol is to assess feasibility. Are the instructions clear? Is it realistic to ask people to focus on the tasks for that long? The second reason is that almost everyone involved in this research has experience with the natural versions of the substances we use, whereas we use the synthetic versions for the study. The question of whether the natural and synthetic versions are comparable is an open one. In addition, the context is different. How is it to have these experiences in a clinical setting like a hospital. How can we facilitate the experience by making this clinical context a bit more pleasant? 

Jasper: That is actually very interesting to hear. I always thought that self-experimentation was historically emphasized specifically for research with psychedelics but it’s actually a broader norm that researchers test their protocols themselves first. When it comes to modern research involving psychedelics, this becomes complicated because of the stigma on psychedelic use generally and self-administration by researchers specifically, based on historical examples like Timothy Leary for example. 

Michiel: Indeed. Certain effects are intuitively experienced like Stroop or Simon effects. These effects are so “right in your face” that you immediately understand what they are when performing the task. This facilitates an understanding of what cognitive conflict means. In certain fields, it is standard practice for researchers to use themselves as participants, for example in the field of visual processing where you need a large number of trials and highly trained participants that need to fixate on a specific point for two hours at a time. The average university student would not be able to do this. Of course this can only be done for very basic processes where understanding the aims of the study does not influence the results. 

Jasper: Really interesting, I never knew.

Michiel: Yeah, it’s funny how this topic came up now. I had never thought of it as an argument in favor of self-administration before. 

Jasper: Besides the informal stigma on self-administration, I assume there is some formal reason why the board of ethics would not authorize it. Did you try to get permission and fail and, if so, what was their reasoning?

Michiel: No, that’s a misunderstanding. We toyed with the idea for a bit while writing the protocol. But METC permission is already very difficult in and of itselft. We wanted to make it less complicated for ourselves. There’s also the question of the public perception of our research. I remember someone pointed out to me that it would be rather awkward if one of my PhD students and I were seen coming out of the experiment room smiling and giggling about the bizarre experience we just had, despite the best intentions on our part. 

Jasper: Of course what Leary did was quite different. He took psychedelics with his students in an informal setting as a means of researching them. He didn’t do this to establish the feasibility of a protocol he was working on or anything. But the stigma that resulted from that period is still felt today.

Michiel: Yeah but of course there’s a broader question at play here. What is the role of self-administration by clinicians. I interviewed a psychiatrist for my book who said he doesn’t need to have tried all the medications he gives his patients himself first. Some psychiatrists disagree though, and argue that it is actually important to try certain medications such as SSRIs or Ritalin to get an understanding of their subjective effects.  Still, I’m not sure whether I support self-administration of the sort that we were planning to do. You could probably gain similar insights by using a few experienced users, you don’t need the first-person experience for that. I personally find self-administration interesting mostly as a source of inspiration, which I see a lot in other psychedelic researchers who use it a lot in their personal life. It’s one thing to use it as a personal source of inspiration and quite another to do so to improve the research that you’re doing. 

This is the first part of Jasper and Michiel’s conversation. The next part will be on the placebo effect. Follow OPEN on Instagram, LinkedIn, and Twitter – or subscribe to OPEN’s Newsletter – to stay up to date for its release.

How AI and language can help predict psychedelic treatment outcomes

Language is increasingly being used as a diagnostic tool in biomedical research and has recently begun to be leveraged in psychedelic research. It turns out analysing language through machine learning can help increase diagnostic accuracy and predict psychedelic treatment outcomes, which will play an important role in the future of psychedelic research.


Illustration: Anna Temczuk

Language as a diagnostic tool

Sigmund Freud and Carl Jung are arguably the most influential figures of the 20th century when it comes to psychological functioning and the human mind. Although their theories about the psyche eventually differed, they both considered language as a manifestation of the unconscious. Indeed, Freudian psychoanalysis proposed free association as a way of gaining access to unconscious processes, while Jungian psychology considered every act of speech as a psychic event, with each word carrying particular archetypal energies. Fast forward 100 years, innovations in biomedical science and technology have transformed language into a diagnostic tool for both affective and degenerative neuropathology, and language is increasingly being used as such in psychedelic research. 

Natural Language Processing, also known as NLP, is a field combining linguistics, computer science, and artificial intelligence. It applies computational techniques to the analysis and synthesis of natural language. One of the problems with natural language is that it often contains ambiguities in meaning, also known as semantic ambiguities, which are easily detectable by humans but not so much by computers. Luckily, models such as distributional semantics, count vectorisation and encoder-decoder modeling help decipher semantic ambiguities. Since its development, NLP has predominantly been used as an automation tool for google searches, spam email categorisation, voice recognition, and translations, but it is increasingly being used as a diagnostic tool in medicine. 

A few years ago, a team of researchers in Canada were able to identify linguistic features within narrative speech that were specific to Alzheimer’s Disease. Semantic impairment, acoustic abnormality, and syntactic impairment were all factors enabling the accurate identification of Alzheimer’s, based on patients’ short descriptions of a picture.

This led to the realisation that beyond its unconscious, psyche-revealing properties, natural language might also possess neuropathology-revealing properties. So what if language could be used as a biomarker for psychosis or affective disorders? More importantly, what if language could be used as a predictor of treatment outcome? It turns out these tools have already begun to be leveraged in psychedelic research.

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Around four years ago, a team of researchers from Buenos Aires University’s Applied Artificial Intelligence Lab and Imperial College London’s Psychedelic Research Group decided to test a combination of NLP and machine learning. They tested this combination both as a diagnostic tool for patients suffering from treatment-resistant depression, and as a predictor of treatment outcome following a psilocybin challenge. 

Participants first underwent a psychological interview known as an Autobiographical Memory Test, an interview used to assess the degree of specificity of autobiographical memory. This interview was analysed using an NLP method known as Emotional Analysis, which quantifies the emotional content of spoken or written text. The NLP output was then fed as input into a machine learning algorithm, known as a classifier, trained at recognising depressed patients. 

On the basis of emotional analysis and specifically the use of positive words, which were less frequently used in depressed patients compared to healthy controls, the classifier was able to differentiate between depressed patients and healthy controls with a mean accuracy of 82.85%, close to 15% better than the mean accuracy of general practitioners unassisted by screening tests.  

Accurate Predictions

Perhaps more impressive than its ability to differentiate between depressed patients and healthy controls, was the classifier’s ability to differentiate between treatment responders and non-responders. Based on the same parameters it had previously used to diagnose depressed patients (NLP output and positive word frequency), the classifier was able to predict which patients would respond to a psilocybin challenge and which would not. 

Only the patients identified as “responders” were given the psilocybin challenge, whereas the “non-responders” were removed from the treatment arm. This manoeuvre had the effect of improving overall treatment response by 34% compared to the original experiment.  

Last year, a team at Johns Hopkins University used a similar approach to predict changes in substance use following a psychedelic challenge. They recruited individuals who reported quitting or reducing a number of addictive drugs following a psychedelic experience, and asked them for a verbal narrative of the experience.

They used an NLP method known as Latent Semantic Analysis, which analyses the relationship between semantic structures across different texts, to derive topic models that described the psychedelic narratives. These topic models were fed as input into three different machine learning algorithms to predict long-term drug reduction. The machine learning algorithms had an average predictive accuracy of 65%, and additional analyses revealed between-group differences in psychedelic experience narratives based on the derived topic models.

John Hopkins’ semantic analysis of psychedelic narratives and Buenos Aires University’s use of machine learning to identify patients suffering from depression, are two early but powerful examples of the ways in which language can be leveraged in psychedelic research through new technology.

The combination of NLP and machine learning as methods to analyse language have reliably shown their value as both diagnostic and predictive tools, and can be used to optimise clinical trials. They allow for a more personalised treatment, whereby non-responders are spared the emotional rollercoaster of an acute psychedelic experience. 

Freudian psychoanalysis, Jungian psychology and NLP share the conception that hidden semantic structures within language are associated with underlying processes, whether psychological, social, or physiological. A century ago, language was the glass through which Freud saw the unconscious mind. Today, language analysed by machine learning may very well be one of the prisms through which we can come to understand the psychedelic experience.

References:

1. N.B. This is different from “Neuro-linguistic programming” (NLP), which is a form of psychotherapy developed in California in the 1970s, mainly used as a method of personal development by promoting skills including communication.

2. Fraser, K. C., Meltzer, J. A., & Rudzicz, F. (2016). Linguistic Features Identify Alzheimer’s Disease in Narrative Speech. Journal of Alzheimer’s disease : JAD, 49(2), 407–422

3. Carrillo, F., Sigman, M., Fernández Slezak, D., Ashton, P., Fitzgerald, L., Stroud, J., Nutt, D. J., & Carhart-Harris, R. L. (2018). Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. Journal of affective disorders, 230, 84–86

4. Carey, M., Jones, K., Meadows, G., Sanson-Fisher, R., D’Este, C., Inder, K., Yoong, S. L., & Russell, G. (2014). Accuracy of general practitioner unassisted detection of depression. The Australian and New Zealand journal of psychiatry, 48(6), 571–578.

5. The original experiment consisted of a combination of psychotherapy and pharmacological treatment with psilocybin that resulted in 41% treatment response. By differentiating between treatment responders and non-responders this experiment resulted in 75% treatment response

6. Cox, D. J., Garcia-Romeu, A., & Johnson, M. W. (2021). Predicting changes in substance use following psychedelic experiences: natural language processing of psychedelic session narratives. The American journal of drug and alcohol abuse, 47(4), 444–454

A Really Good Day : How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life

A Really Good Day : How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life. Ayelet Waldman. Little, Brown Book Group. ISBN: 978-1472152893

A first-hand account of microdosing and its positive effects. Waldman charts her experience over the course of a month and looks into the newest research and policies governing LSD. This book will be interesting for anyone curious about how microdosing LSD can affect daily living.

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Mapping an Agenda for Psychedelic-Assisted Therapy Research in Patients with Serious Illness

Abstract

Background: With support from the Radcliffe Institute for Advanced Study at Harvard University, we convened researchers representing palliative care, psychosocial oncology, spiritual care, oncology, and psychedelic-assisted therapies. We aimed to define priorities and envision an agenda for future research on psychedelic-assisted therapies in patients with serious illness. Over two days in January 2020, participants engaged in an iterative series of reflective exercises that elicited their attitude and perspectives on scientific opportunities for this research. Objectives: The aim of the study is to identify themes that shape priorities and an agenda for research on psychedelic-assisted therapy for those affected by serious illness. Methods: We collected data through preconference interviews, audio recordings, flip charts, and sticky notes. We applied thematic qualitative analysis to elucidate key themes. Results: We identified seven key opportunities to advance the field of psychedelic-assisted therapies in serious illness care. Four opportunities were related to the science and design of psychedelic-assisted therapies: clarifying indications; developing and refining therapeutic protocols; investigating the impact of set and setting on therapeutic outcomes; and understanding the mechanisms of action. The other three pertained to institutional and societal drivers to support optimal and responsible research: education and certification for therapists; regulations and funding; and diversity and inclusion. Additionally, participants suggested epistemological limitations of the medical model to understand the potential value and therapeutic use of psychedelics. Conclusions: Medicine and society are witnessing a resurgence of interest in the effects and applications of psychedelic-assisted therapies in a wide range of settings. This article suggests key opportunities for research in psychedelic-assisted therapies for those affected by serious illness.

Beaussant, Y., Tulsky, J., Guérin, B., Schwarz-Plaschg, C., Sanders, J. J., & Radcliffe Institute for Advanced Study Working Group on Psychedelic Research in Serious Illness (2021). Mapping an Agenda for Psychedelic-Assisted Therapy Research in Patients with Serious Illness. Journal of palliative medicine, 24(11), 1657–1666. https://doi.org/10.1089/jpm.2020.0764

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Combining Psychedelic and Mindfulness Interventions: Synergies to Inform Clinical Practice

Abstract

Psychedelic and mindfulness interventions have been shown to improve mental ill-health and wellbeing, with a range of clinical processes and effects in common. However, each appear to contain specific challenges in the context of mental health treatment. In this Perspective, we focus on a set of distinct affordances, “useful differences”, within psychedelic and mindfulness interventions that might address common challenges within the other intervention. Accordingly, we propose a set of applied synergies, indicating specific ways in which these two promising interventions might be combined for greater benefit. Metaphorically, on the journey toward mental health and wellbeing, we propose that psychedelic treatments may serve the role of Compass (initiating, motivating, and steering the course of mindfulness practice), with mindfulness interventions serving the role of Vehicle (integrating, deepening, generalizing, and maintaining the novel perspectives and motivation instigated by psychedelic experience). We outline a set of testable hypotheses and future research associated with the synergistic action of psychedelic and mindfulness interventions toward improved clinical outcomes.

Payne, J. E., Chambers, R., & Liknaitzky, P. (2021). Combining Psychedelic and Mindfulness Interventions: Synergies to Inform Clinical Practice. ACS pharmacology & translational science, 4(2), 416–423. https://doi.org/10.1021/acsptsci.1c00034

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Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice

Abstract

Psychedelic Harm Reduction and Integration (PHRI) is a transtheoretical and transdiagnostic clinical approach to working with patients who are using or considering using psychedelics in any context. The ongoing discussion of psychedelics in academic research and mainstream media, coupled with recent law enforcement deprioritization of psychedelics and compassionate use approvals for psychedelic-assisted therapy, make this model exceedingly timely. Given the prevalence of psychedelic use, the therapeutic potential of psychedelics, and the unique cultural and historical context in which psychedelics are placed, it is important that mental health providers have an understanding of the unique motivations, experiences, and needs of people who use them. PHRI incorporates elements of harm reduction psychotherapy and psychedelic-assisted psychotherapy, and can be applied in both brief and ongoing psychotherapy interactions. PHRI represents a shift away from assessment limited to untoward outcomes of psychedelic use and abstinence-based addiction treatment paradigms and toward a stance of compassionate, destigmatizing acceptance of patients’ choices. Considerations for assessment, preparation, and working with difficult experiences are presented.

Gorman, I., Nielson, E. M., Molinar, A., Cassidy, K., & Sabbagh, J. (2021). Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice. Frontiers in psychology, 12, 645246. https://doi.org/10.3389/fpsyg.2021.645246

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Associations between lifetime classic psychedelic use and markers of physical health

Abstract

Background: In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health.

Aims: The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health.

Methods: Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates.

Results: Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once.

Conclusion: The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.

Simonsson, O., Sexton, J. D., & Hendricks, P. S. (2021). Associations between lifetime classic psychedelic use and markers of physical health. Journal of psychopharmacology (Oxford, England), 35(4), 447–452. https://doi.org/10.1177/0269881121996863

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30 April - Q&A with Rick Strassman

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