OPEN Foundation

OPEN Foundation

SUSTAINABILITY & RECIPROCITY

Art by Aine Design 

We are extremely happy to be able to socialise with all of you soon at ICPR 2022. Yet we are fully aware of multiple ongoing crises right now. Out of care and concern for our living environment and other species, we decided to reduce ICPR’s ecological footprint per person compared to earlier conferences.

We have opted for vegetarian, mostly organic meals, have created a digital conference booklet instead of a printed one, and have dispatched with the tradition of physical swag bags.

We also reduced our oversees marketing, introduced livestream-tickets (including scholarship tickets) and have now started a fundraiser to compensate for the conference’s carbon footprint and to give back to the cultures whose knowledge informs psychedelic science today.


Green fundraiser
To compensate for the travel emissions involved in getting speakers and attendees to Haarlem, we have launched a fundraiser through One Tree Planted. OPEN will ‘plant’ the first few thousand trees, and we hope to triple or quadruple that number with your help. Go to our fundraiser on One Tree Planted to contribute.

One Tree Planted is a non-profit organization focused on global reforestation. Your donation is tax-deductible.

Reciprocity fundraiser
We acknowledge and honor the responsible relationships that indigenous peoples have forged with psychedelic plants over the past centuries. We recognize that the Global North benefits from their knowledge, and we believe that it is critical to support the organizations working to conserve the biocultural communities that have taught – and continue to teach – the rest of the world about how entheogenic plants can benefit individuals and societies. 

Our partners at the Chacruna Institute recently launched the Indigenous Reciprocity Initiative, which we applaud and want to support with a second ICPR fundraiser. Please consider donating if you feel that you have benefited from psychedelics in any way.

The Indigenous Reciprocity Initiative (IRI) is a community-directed biocultural conservation program connecting directly with grassroots Indigenous organizations with the aim of ‘giving back’ to the cultural regions that support indigenous plant use and knowledge. IRI created a pool of funds that supports Indigenous initiatives with a proven track record, addressing a broad range of efforts from food security and environmental health, to economic and educational support.

IRI strives to foster a relationship of reciprocity between the rapidly growing industry generated by the mainstreaming of psychedelics in the Global North, and the Indigenous peoples who have historically received little benefit from the commercialization of their cultural and biological heritage. 

No swag bags, but…
We’re not handing out notepads and swag bags anymore, so we kindly request that all attendees bring their own writing gear. But, of course, we will not let our guests go home entirely empty-handed either! There will be some surprises that do not cause unnecessary garbage.

Previewing ICPR 2022: A Full Week of Psychedelic Science

The Interdisciplinary Conference on Psychedelic Research 2022 is now only a few weeks away, and we are happy to announce the full program to ICPR 2022.

Full Programme

In its preliminary form, the  ICPR 2022 Conference Programme has been posted on the ICPR website. In the coming weeks, we will highlight its parts separately.

With the Conference Programme now live on the ICPR website, we would like to showcase all that is happening in Amsterdam and Haarlem around our conference between the 17th and 24th of September. Because outside the conference, there will be tons to do in Haarlem and Amsterdam in the week before and after ICPR, organized or co-hosted by the OPEN Foundation. Like workshops, parties and events.

ICPR 2022 GENERAL INFO

ICPR 2022 will be held from Thursday, September 21st until Saturday, September 23rd. Around 80 speakers and poster presenters will hold live presentations at the stunning Philharmonie building, a 19th-century concert hall in Haarlem. 

Haarlem is a small city close to Amsterdam, about 20 minutes from Amsterdam Central Station and a 10-minute walk from Haarlem’s. We encourage people to arrive by public transport and foot.

ICPR is attended by some of the biggest names in psychedelic research and therapy, including Rick Doblin, Erika Dyck, Paul Stamets, Amanda Feilding, Bernardo Kastrup, and many other people who have played active roles in the development of the psychedelic field in the past five decades. Alongside these established researchers, upcoming talents in the field will give presentations and present posters that provide a brief overview of their most recent work. Free organic and vegetarian lunch, coffee, tea, snacks, and more are included with an in-person ticket.

As expected of the OPEN Foundation and from previous conferences, this edition will again contain high-quality science and critical perspectives from various academic disciplines, varying from neuroscience to policymaking, philosophy and the humanities.

interesting topics

For anyone interested in the ideas and challenges surrounding psychedelics, as they again become a part of contemporary society, ICPR 2022 is an embarrassment of riches! 

  • novel treatment advances with 5-MeO-DMT (5-methoxy-dimethyltryptamine), a substance that is considered to be the most potent psychedelic. 
  • Its relative, DMT, is also being explored and discussed for individuals who are suffering from major depressive disorder (MDD) . 
  • Other compounds known as entactogens, which include MDMA and its analog ‘methylone’, are presented for both MDD and post-traumatic stress disorder (PTSD).
  • Beyond psychiatry, ICPR will examine the potential use of LSD and psilocybin in navigating end-of-life anxiety for the terminally ill, as well as the use of psilocybin for migraines and cluster headaches.

Additionally, ICPR 2022 will explore the potential of novel compounds (e.g. psychoplastogens) versus existing compounds like psilocybin and LSD, how to overcome challenges around trial design like issues around placebos, expectation, hype, the ‘Michael Pollan effect’, and the potential obstacles to psychedelic therapy becoming a reality in the near future.

We’ll discuss some of the most important questions IN to psychedelic therapy today: 

  • What dominant discourses, such as the ‘psychedelic renaissance’, should we challenge?
  • What is the role and function of a therapist’s self-experience with psychedelics?
  • How can we mitigate transgressions and abuse?
  • How can we include patient perspectives in setting up clinical trials?
  • How can we consider inclusion, diversity, and anti-racism within the field of psychedelics? 
  • What’s the roles and risks of businesses and patenting in the future psychedelic commercial field?
  • What should psychedelic education look like?
  • How will psychedelic therapy legally be implemented in existing health care stuctures?
ICPR 2022 is almost here. Get your tickets before we sell out.

ICPR Side Events

Saturday, September 17th

Join us in starting ICPR 2022 by tuning into the right mindset! This event consists of an immersive 4-hour musical and meditative journey performed by a group of highly talented musicians and pioneering sound engineers. It is entirely free and donation-based, and will be broadcast live from the legendary Wisseloord Studio in Hilversum, where artists such as Michael Jackson, Paul McCartney, The Police, Foo Fighters, Electric Light Orchestra and many others have recorded albums. Everyone attending ICPR (either in-person or online) can experience this amazing journey from their own homes. Do not miss it!

Wednesday, September 21st

Psychedelic Science, Ethics & Business

ICPR starts off this year with the Psychedelic Science Ethics & Business event. The day will be dedicated to an in-depth and critical discussion about the intersection of psychedelic research, treatments, and investment. We will discuss how the growing economy around psychedelics impacts science and therapy. The event consists of various leading experts from different fields, including psychedelic businesses, academia, non-profit organisations, and investment companies.

We’ll address questions such as: What is needed to bridge the gap between doing scientific research in a lab environment and eventually practising psychedelic therapy with patients? How can investment and the proliferation of startups be made compatible with core values and public benefit, including optimal patient care, and accessible and equitable treatments? What are potential business models for psychedelics? What does that mean for access and quality? And much more!

If you’re an entrepreneur, investor, executive, researcher, clinician, or someone who cares about these developments, you will walk away from this conference with unique insights into how psychedelic science can be translated into practice.

Psychedelic Workshops

Are you more interested in the practice of psychedelic therapy or learning about the most recent developments that surround it? We’ve got you covered! On Wednesday, September 21st, we have three amazing workshops to choose from facilitated by the leading experts in their respective fields.

The Psychotherapy with Psychedelics Workshop is dedicated to current and future therapists who are interested in the practice of psychedelic-assisted psychotherapy. Important learning objectives include the core competencies and skills for therapists working with psychedelics, key elements for preparing patients and helping them with integration after psychedelic sessions or getting a better understanding of different psychological and neurobiological explanatory models for the therapeutic effects of psychedelics.

During this workshop, people will learn from the world’s most experienced clinicians in the field, including clinical psychologists Janis Phelps, PhD and William (Bill) Richards, PhD, and psychiatrist Torsten Passie, MD. Please note that this workshop is already sold out!

The Music as/for Psychedelic Therapy Workshop is hosted by Mendel Kaelen, who is the founder and CEO of Wavepaths. During this workshop, you will learn about how you can effectively guide patients and optimise therapeutic outcomes through the combined use of psychedelics and music.

The Breathwork as Psychedelic Therapy Workshop will be hosted by Katrien Franken and OpenUp. During this workshop, you will learn about and engage inbreathing exercises. This practice has been used for centuries by ancient and native cultures for cultivating expanded states of consciousness in order to facilitate transformative experiences that deepen the connection between body and mind.

OPEN Foundation director Joost Breeksema was on the Psychedelics Today podcast to talk about ICPR.

SPECIAL EVENTS AT ICPR 2022

With approximately 100 presenters, more than 60 poster presentations, various plenary lectures, panel discussions, Q&A sessions, and lots of interaction with other attendees, you become a part of the pioneering and leading scientific conference in Europe since 2007. On top of that, there will be a musical soundscape hosted by Wavepaths and live music sessions performed by Spinoza. Each day will have special events that you may attend and that are listed below.

Thursday, September 22nd

Merge
Come join us on the evening of ICPR’s first day with MERGE. This immersive, experiential gathering of the psychedelic research community will be hosted by Tactogen and ICPR, and is open to everyone.

Whether you are deeply involved in psychedelic research or are interested in getting more involved, all present will unite and come together for an evening dedicated towards creating connection, relaxation and inspiration. Dr. Tehseen Noorani and Scarlet Masius will be leading groups through interactive games to build collaborative opportunities for interdisciplinary research. Note that the attendance for this special event is free, but registration is required (maximum of 150 people).

Vincent Moon
The second event of the night is an art performance by Vincent Moon, known for his “live-cinéma.” Vincent’s performance improvises live-edited images, music and film  on-stage – to explore the boundaries between cinema, music, and expanded forms of modern rituals. Each performance contains a unique combination of films and music based on the recordings of his own Collection Petites Planètes, and created partly in collaboration with writer and explorer Priscilla Telmon. All the performances are site-specific and sometimes involve local musicians and participants, leading to a new film being created on the spot every time.

Friday, September 23rd

Networking dinner
On the second day of ICPR, there will be a professional networking dinner for clinicians and therapists currently involved or planning to become involved in clinical research or treatment with psychedelics. This event will only be accessible to professional ticket holders. Be sure to get your ticket soon, as only a few tickets are remaining!

Saturday 24th September

Descending the Mountain
All good things unfortunately must come to an end,but we will close things out with a bang. We’ll celebrate ICPR’s final day with a screening of the phenomenal documentary Descending the Mountain, followed by a Q & A with the movie’s producer, Annette Badenhorst.

ICPR Afterparty
To top it all off, we have organised an official ICPR Afterparty. This is free for all attendees, but registration is required. Be sure to do this on time so you do not miss it! The afterparty will contain amazing music, with an immersive, 360 surround sound system and artists such as Tripping Jaguar, ICPR presenters MK Ultra and Baham Collective, and many others yet to be announced. The maximum number of attendees is 500.

OPEN Co-Founder Joost Breeksema on psychedelics today to talk about icpr

OPEN’s Executive Director, Joost Breeksema, joined David Drapkin on episode 340 of the podcast of Psychedelics Today – one of ICPR’s platinum partners. Joost and David discussed a wide variety of topics, from drug policies to ethics, the nature of reality and the latest details about ICPR

Joost Breeksema is a psychiatry researcher as well as the executive director of OPEN since 2007. He’s a psychedelic enthusiast with a background in philosophy. He remarked on the importance of psychedelics in mental health treatments, which, as he describes “confront people with their own existence, with their place in the universe, with how they relate to themselves and to others.”

Joost believes in the importance of bringing together all the actors involved in order to be ready when these substances become legal, from researchers to health care insurance and policymakers.

Here’s a snippet from the podcast. You can listen to the entire episode from Psychedelics Today here

Caution

As advances in psychedelic research keep on growing, Joost asks for caution. There needs to be a balance between hype and hope, he says. There is still a long road ahead in order to get a “safe and sustainable psychedelic treatment”, as he put it. Joost points out that luckily, the Netherlands is one of the leading countries in relation to drug policies. Its decriminalization model has been working for decades and there are lots of efforts being put into harm reduction approaches. Nevertheless, there are important changes that need to be made in order to help the improvement of psychedelic research. 

Joost comes from a background in philosophy, and although he has spent recent years closer to research and therapy about psychedelics, the metaphysical angle on the psychedelic world still interests him mostly. The “I” in ICPR stands for ‘interdisciplinary’, so Joost was glad to shine a light on his fondness for Bernardo Kastrup – who is a computer scientist and philosopher who will be one of the keynote speakers at the upcoming conference.

ICPR 2022 is almost here. Get your tickets before we sell out.

Bernardo Kastrup is one of the main proponents of metaphysical idealism and has a PhD in philosophy and computer science. He has explained reality as “best imagined as mathematical equitations floating in empty space” in one of the interviews he has given. 

Joost is looking forward to his talks and the questions Kastrup poses: “How can we understand consciousness? How can we use psychedelics as tools to study consciousness? Can this tell us anything about ontology, the nature of reality or the nature of knowledge? I think this is one of the speakers that I’m looking most forward to seeing”.

Bernardo Kastrup is one of the speakers at ICPR Joost is most looking forward to

ICPR will be one of the places to discuss all these topics. This year’s conference will also have one extra day at the very beginning, September 21, dedicated to ethics and businesses. Professionals from different backgrounds will come together to share their different opinions. As more people find the psychedelic world appealing, David asked Joost about the importance of diversity and inclusion, sometimes easy to forget when money is involved.

After two years of the pandemic, and with the previous ICPR edition being online, Joost is thrilled for the upcoming conference and believes it is a great opportunity to learn, share and connect with different professionals and enthusiasts. He emphasized the different perspectives that will be covered, also outside of the medical world, like the arts, culture, and media and the separate workshops that are given around the conference.

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.

In loving memory of ann shulgin

Ann Shulgin, the wife of renowned chemist genius Alexander “Sasha” Shulgin, passed away at age 91 on July 9. Both were extraordinary human beings and pioneers in the field of psychedelic research, particularly due to their significant contribution in the development and therapeutic use of (novel) psychedelic compounds. To honor both, we gladly share some of her history and both their legacy.

Laura Ann Gotlieb was born in Wellington, New Zealand on March 22, 1931, and shortly thereafter lived an extraordinary life, spending her time in various places around the world, including Italy, Cuba, Canada, and finally the Bay Area in the US when the Beatnik generation was in full swing. She got married, and divorced, three times and then met her fourth husband, Sasha Shulgin, in the Fall of 1978. After three years of spending time together, they got married in Sasha’s backyard during a surprise ceremony by an official of the Drug Enforcement Administration. Yes, the DEA. 

Ann used to work as a medical transcriber in San Francisco and probably became familiar with Jungian psychology through her third husband who was a Jungian psychiatrist. It was only later after marrying Sasha that she got involved in the development of novel psychedelic compounds. During this period, she started practicing psychedelic-assisted therapy in conjunction with MDMA or 2C-B at a time when these substances were still legal. She became a strong adherent of Jungian psychoanalysis and believed that psychedelics have huge potential for self-actualization when used within such a framework. 

The development and various discoveries of other psychedelics together led to the authoring of two books: PIHKAL: A Chemical Love Story and TIHKAL: The Continuation. Respectively, these titles are  acronyms for “Phenethylamines/Tryptamines I Have Known and Loved.” Partly fictional autobiography and partly considered “pretty much cookbooks on how to make illegal drugs” by the DEA, both Ann and Sasha were filled with passion and courage to describe no more than over 179 different psychedelic compounds – all with the main goal of releasing information about psychedelic compounds and its therapeutic properties to the public. Psychedelics, they both believed, were there as valuable tools for human beings to explore and self-actualize. Ann briefly appears on a recent episode of Hamilton’s pharmacopeia, where we see that she continued to live in the house that contains the original lab of Sasha.

We are forever grateful for their contribution to the development and therapeutic use of (novel) psychedelic compounds and aim to continue their legacy. 

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.

What are the effects of psychedelics on neuroplasticity?

Psychedelics appear to consistently produce long-lasting behavioural changes in the individuals who use them. Research focus has recently shifted to understand the accompanying changes in brain function and structure, which are hypothesised to occur through neuroplasticity. In this interview, Cato de Vos, MSc, explains what neuroplasticity is, how it can be measured in humans and animals, its importance in brain development, and the mechanisms by which psychedelic compounds and other practices can generate it.


Interviewee: Cato de Vos

Over the past couple of decades, accumulating evidence has shown that psychedelics consistently produce strong subjective effects, often leaving a perennial imprint on the individuals ingesting them. 

The subjective effects of the acute psychedelic experience are remarkable in and of themselves. At higher doses, they may occasion mystical-type experiences, considered by the individuals who have them as some of the most meaningful experiences of their lives, on par with one’s wedding day or the birth of a child. Perhaps even more remarkable are the sustained effects of these experiences on positive changes in attitudes and behaviours, lasting up to 14 months following the experience in one study.

Other studies have found similar long-lasting effects of these acute psychedelic experiences on depressive symptoms in patients with treatment-resistant depression, on smoking cessation in nicotine-dependent individuals, and on alcohol consumption in alcohol-dependent individuals. In each case, the quality of the acute psychedelic experience predicted the long-term changes from 6 to 12 months later. 

It is clear from the available scientific literature that psychedelics have an important therapeutic potential that needs to be investigated, and that therapeutic outcome may be determined by the subjective psychedelic effects. As a neuroscientist however, it is challenging to consider long-term behavioural changes without any accompanying structural or functional brain alterations. These findings pose the following question: do psychedelics affect brain structure and/or function in a way that can lead to long-term changes? And if so, by which processes?

Cato M. H. de Vos holds an MSc in neurobiology at the University of Amsterdam. She currently works as a research-assistant at the mental health organisation 1nP in the Netherlands where she assists Dr. Heval Özgen and Gerard van Kesteren (PhD cand.) in several clinical trials investigating the safety, feasibility, and efficacy of MDMA-assisted therapy. Soon, she will also start a part-time study in Psychology to become a therapist. In September 2021, she published a systematic review in Frontiers in Psychiatry, with Natasha L. Mason, PhD., and Professor Kim P. C. Kuypers, PhD., from Maastricht University. 

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The aim of the paper was to review the evidence pertaining to psychedelics’ ability to induce molecular and cellular adaptations related to neuroplasticity, and to see whether they paralleled clinical effects. In total, 16 preclinical and 4 clinical studies were reviewed, revealing that a single administration of a psychedelic produced rapid, multi-level changes in plasticity-related mechanisms, including changes in the expression of BDNF, a neurotrophin involved in the growth, maturation, and maintenance of neurons.

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Q&A with Cato de Vos, MSc.

Question 1. What is neuroplasticity? What is its role in brain development?

Neuroplasticity is the brain’s ability to change throughout life. These changes may occur in cell structure, known as structural plasticity, or in the efficacy of synaptic transmission, known as functional plasticity. An example of structural plasticity is dendritogenesis, where dendrites – the receiving end of neurons – expand, and an example of functional plasticity is synaptogenesis, where new synapses – neuronal junctions – are formed, enabling better communication between neurons. 

Structural and functional plasticity are interconnected processes at a molecular and subcellular level, which eventually give rise to changes at the behavioural level. These changes allow your brain to adapt and change, promoting the ability to learn new things, enhancing your existing cognitive capabilities, supporting recovery from strokes and traumatic brain injuries, strengthening brain areas where functionality has been lost or has declined, and boosting brain fitness. However, neuroplasticity is a double-edged sword. Changes in the structure and function of the brain can confer adaptive benefits but can also lead to maladaptive disadvantages. To illustrate, misdirected activation of neuroplasticity can cause forms of severe tinnitus (‘ringing in the ears’) and neuroplasticity in the brain’s reward system induced by repeated use of certain drugs, such as cocaine, leads to more compulsive drug use. So the risk / benefit ratio also depends on the area where neuroplasticity is occurring.

For a long time researchers believed that the brain stopped developing during adolescence, and that there was a fixed number of neurons in the adult brain that could not be replaced when the cells died. In the 1960s, neurobiologist Joseph Altman discovered the creation of new neurons in the brain. His discovery was largely ignored, until the rediscovery of adult neurogenesis by Elizabeth Gould in 1999. Ensuing research on neurogenesis has since shown that the brain can change throughout life. Specifically the hippocampus, that part of the brain involved in spatial memory, learning processes and even emotion, continues to form new neurons throughout life. Thus,  neuroplasticity is the process by which the brain can modify, change and adapt structure and function in response to the environment.

Question 2. How can neuroplasticity be measured?

There are different ways to measure neuroplasticity in animals and in humans, but it really depends on the level you’re looking at. Neuroplasticity occurs at different levels in the brain (molecular and cellular), involves communication between different brain regions (structural and functional), and eventually affects behaviour, so it depends on the particular area that is being studied. When looking at the molecular level, for example, certain protein levels can be measured. If certain proteins are more expressed than others, then you can infer that they play a bigger role in the process, which can be an indication of neuroplasticity, although it’s a fairly indirect measure.

At a cellular level, a microscope can be used to examine dendrites. If you see that neurons have progressively more elaborate dendrites, that they look like a tree with more branches than before, then you can assume dendritogenesis is at work. 

This type of examination can be performed in animals, but is not as easy in humans, whose brains are not as easily available for research. An alternative is measuring the levels of certain proteins – like BDNF –  in the blood and other parts of the body. With humans, unlike with animals, biological and psychological parameters can be combined, which enables you to investigate the relation between biological and behavioural changes. That’s one of the things that is lacking in animal research: you can’t ask a mouse how it’s feeling. 

Question 3. By which mechanisms do psychedelics induce neuroplasticity?

The changes in neuroplasticity induced by psychedelics are believed to result from the neurobiological pathways they activate. Classic psychedelics act on a serotonergic receptor called “2A” (5-HT2AR). When psychedelics activate this receptor, specific pathways – cascades of different proteins communicating and transferring a signal – are activated. These cascades, or pathways, are different to non-psychedelic-induced activations of the same receptor. 

Following the activation of these cascades, two neurotransmitter systems are activated: the inhibitory serotonergic system, and the excitatory glutamatergic system. The activation of these systems leads to the release of both serotonin and glutamate and subsequently, brain-derived neurotrophic factor (BDNF), a direct indicator of neuroplasticity. Indeed, high levels of BDNF in the brain are associated with increased neuroplasticity. Psychedelics also influence neuroplasticity indirectly, by affecting the transcription of plasticity-related genes and proteins, which modulates the expression of other genes and proteins involved in neuroplasticity. 

Not every study shows that psychedelic administration necessarily stimulates neuroplasticity. It’s therefore not possible to say that it always happens, but there are some good indications that it does. There is also a lot of uncertainty when it comes to the molecular mechanisms I mentioned because measuring molecular cascades is very challenging, so more research is needed to draw definite conclusions.

Question 4. Have the clinical findings in humans mirrored the preclinical findings in animals so far ?

It’s hard to compare the two. Since different techniques are used to investigate humans and animals, making any comparison is like comparing apples and oranges. They both have their pros and cons. 

Clinical research can investigate both the biological and psychological parameters, which is good because you can then investigate correlations between the two. I believe the psychological state is important if you want to be able to observe improvements in the state of a patient, but it’s more difficult to measure direct biological parameters such as cerebrospinal fluid BDNF, like you can in animals. There are many translational issues, which is why we need to keep combining clinical and pre-clinical research, and be mindful of these limitations.

Question 5. Can neuroplasticity alone be therapeutic? What are your thoughts on psychedelic-inspired, neuroplasticity-inducing compounds like TBG, that lack the subjective effects of classic psychedelics?

Personally I am somewhat sceptical about not having the hallucinogenic effects in the context of therapy, but I think it really depends on the reason for psychedelic therapy, because there is a difference between using it for cluster headaches, or PTSD and depression. I believe you need to look at the origin and underlying layers or deep processes within yourself, within your system, that could cause these pathologies which are different in each of these cases. Cluster headaches might be solved with non-hallucinogenic neuroplasticity-inducing compounds, but for the psychiatric disorders – PTSD and depression for example – which are often accompanied by deep-rooted psychological issues, the hallucinogenic effects may be very important. In those cases the peak subjective experience might be necessary, as has already been shown in some studies: the stronger the psychedelic experience, the better the therapeutic outcome. 

That said, I believe that everything is connected – mind and body – and we’re so conditioned to be in our heads and not be aware of what’s going on in our bodies. I feel that psychedelics can restore some of this connection, on a psychological level. Perhaps the hallucinogenic effects may also have a positive impact on cluster headaches. David Olson’s work with TGB is great in that  he is making psychedelics accessible to a bigger audience. A lot of people are excluded from clinical trials because they have a history or family history of certain conditions, and they don’t have access to therapy at all, so this could be a very good thing.

Question 6. Any additional thoughts on neuroplasticity and psychedelics ?

Bear in mind that neuroplasticity can be stimulated by other means, such as taking good care of yourself, engaging in physical activity, meditation, eating healthy food and getting enough sleep. All these can be beneficial and contribute to positive treatment outcomes. We also want to be cautious here, because we don’t know when neuroplasticity stops being a good thing. I believe everything is about balance, so it is good to remain critical. As my colleague Erwin Krediet once said to me: “A plant doesn’t survive when you give it fertiliser every day, it’s too much.”

References:

1. Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–292.

2. Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218(4), 649–665.

3. Carhart-Harris, R. L., Bolstridge, M., Day, C., Rucker, J., Watts, R., Erritzoe, D. E., Kaelen, M., Giribaldi, B., Bloomfield, M., Pilling, S., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Curran, H. V., & Nutt, D. J. (2018). Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology, 235(2), 399–408.

4. Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American journal of drug and alcohol abuse, 43(1), 55–60.

5. Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P. C., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. Journal of psychopharmacology (Oxford, England), 29(3), 289–299.

6. de Vos, C., Mason, N. L., & Kuypers, K. (2021). Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. Frontiers in psychiatry, 12, 724606.

Illustration modified version of Milad Fakurian on Unsplash

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

The Netherlands should be ‘at forefront’ of psychedelic research, says Dutch government

‘The Netherlands can play a pioneering role in developing the right frameworks, limiting potential risks, and designing training programs,’ the Dutch health minister said.

Ernst Kuipers, the new Dutch Minister of Health, Welfare, and Sports, has given his green light to more research in psychedelic therapy, citing “promising results” for typically difficult-to-treat mental illnesses through psychedelics-assisted therapy. His endorsement came in response to questions from three members of parliament from the Dutch political party D66. Kuipers summed up his stance on psychedelic research in a letter directed to the Speaker of the Dutch House of Representatives, and its content is factual and amenable to recent scientific results.

This is a departure for the Dutch government, which in recent years produced more prohibition-focused or avoidant language when it came to issues surrounding psychedelics. The new government has also announced that a state committee will look into the medical use of MDMA – a political compromise arising from the ongoing discussion in the Netherlands about the possible legalisation of MDMA for recreational use.

The new government’s health minister demonstrated conviction about the prominence psychedelic therapy will gain in global healthcare in the coming years, and envisions how the Netherlands could become a leader at the forefront of psychedelic research: “It is paramount that these and other potentially innovative treatments are safely accessible to the target population,” the minister writes. “The Netherlands is one of the leading countries in research into psychedelics in mental health care. In addition, the Netherlands can play a pioneering role in developing the right frameworks, limiting potential risks, and designing training programs for therapists. I am in favour of sharing earned knowledge with parties in the field across different countries.”

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The Netherlands at the forefront of psychedelic research

Apart from MDMA, other psychedelic substances – such as psilocybin1 and ketamine2 – have also demonstrated promise. Kuipers strikes a more cautious tone when speaking about these compounds, affirming the need for more research due to the preliminary nature of current results: “Most of these substances are still in the investigative phase of research. […] It is up to the relevant field parties to follow up on these results. This concerns conducting the necessary research, completing the step-by-step registration process for approval of the substance, and the development of guidelines and protocols necessary for treatment.”

Kuipers further stresses the need for extensive education, the training of psychedelic therapists, and the need to better understand individuals engaged in self-experimentation. He adds that he is “willing to play a facilitating and advising role” in implementing psychedelic research and that his ministry has recently conducted exploratory meetings with researchers and mental healthcare institutions.

He envisions the Netherlands as playing a major role internationally in the coordination and promulgation of psychedelic research, writing that “[t]he Netherlands can stimulate cooperation in a European and international context. In addition, the Netherlands can draw attention to removing barriers in conducting research. In the framework of the United Nations Commission on Narcotic Drugs, I continue to advocate for the removal of barriers to therapeutic use and research into substances on United Nations drug convention lists.

New Research

According to Kuipers, an estimated 1.2 million Dutch citizens currently seek curative mental healthcare each year. Another 215,000 citizens suffer from severe psychiatric illness, a segment of the patient population that is very difficult to treat with current therapies. Kuipers has announced he will allocate 35 million euros to mental healthcare research over the next four years, made available through the Dutch grant organisation ZonMw. Grants will support multidisciplinary studies focused primarily on clinical applied research.

The availability of these funds presents psychedelic researchers with a rare opportunity. Results from these new studies could further elucidate the therapeutic mechanisms by which psychedelics function, thereby putting their clinical application on firmer scientific footing.  Ultimately, Kuiper’s initiative offers the promise of advancing the field beyond its “investigative phase” and imagines a not-too-distant future in which psychedelics are used as legitimate therapeutic agents in clinical contexts, offering hope to the millions who suffer from severe psychiatric illness around the globe.

Barriers to breakthrough therapy status

The three representatives of D66 asked further questions surrounding the current “breakthrough therapy status” of certain psychedelics in the United States. A breakthrough therapy designation is granted to a drug that treats a serious or life-threatening condition, where preliminary clinical evidence indicates that the drug might demonstrate substantial improvement on clinically significant endpoints over available therapies.

Recently, the American Food and Drug Administration (FDA) granted ‘breakthrough therapy status’ to psilocybin for treatment-resistant depression and to MDMA for PTSD. Kuipers explains that a similar status within the Netherlands and other countries in Europe can be attained through organisations such as the European Medicines Agency (EMA).

The minister acknowledges the barriers that still exist for psychedelic research, like “a lack of financial resources for doing the necessary clinical research and developing an approved product for the patient. In addition, psychedelics are substances that are generally non patentable and thus do not fit the ordinary development and revenue model. The potential high costs for the therapeutic treatment with these substances (due to the large amount of hours therapists dedicate to patients during treatment) might also impede incorporating psychedelics as a standard treatment.” 

The issue of the relative expense of psychedelic therapy bears further scrutiny. How, for instance, would the cost of psychedelic therapy compare to that of treatment as usual (TUA) if we take into account factors such as the economic burden of different psychiatric illnesses and/or disability-adjusted life years (i.e,. the number of years lost due to an illness)? To resolve the issue of financial expenditure, cost-effectiveness analyses of psychedelic therapy should be conducted, such as that performed in 20203. This study found that MDMA-assisted psychotherapy versus TUA per 1,000 patients produced savings of up to $103.2 million over 30 years including costs, and surmised that “third-party payers are likely to save money within three years by covering this form of therapy [MDMA].” This, however, is just the conclusion of one study, and the issue of financing deserves further investigation.

Central management and the Netherlands

Kuipers acknowledges the risks involved in the lack of central management of psychedelics. Possible risks include personal experimental use of psychedelics and the development of  commercially exploitative practices that fail to the interests of patients first. Kuipers emphasises the urgency with which these questions need to be answered, and references the Dutch researchers and clinicians who authored Therapeutic use of psychedelics4: “[…] they can develop a framework for this new form of treatment by means of high quality guidelines, standards, and protocols.”

Finally, the new government of the Netherlands has called for more research into MDMA and the possible legalisation of it in the near future. Kuipers mentions that there will be a state committee specifically for MDMA. The state committee will “investigate the status of MDMA in the context of public health and provide advice surrounding the pros and cons of medicinal use by adhering to a multidisciplinary analysis, which takes into account potential risks for health, prevention, and the European context and its relevant treaties.” Kuipers expects to inform the House of Representatives of the committee’s findings in the second quarter of this year.

References:

1. Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., … & Griffiths, R. R. (2021). Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA psychiatry, 78(5), 481-489.

2. Nieuwsuur (2022). Keta kan ‘revolutionair’ middel zijn tegen depressie, maar er zijn ook zorgen.  Consulted on 27 March 2022.

3. Marseille, E., Kahn, J. G., Yazar-Klosinski, B., & Doblin, R. (2020). The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD. PloS one, 15(10), e0239997.

4. Universitair Medisch Centrum Groningen. Manifest therapeutische gebruik van psychedelica. Retreived March 20, 2022.

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