Articles

Open Space Technology

To encourage an active engagement between researchers from different disciplinary backgrounds (a variety of (medical) sciences, social sciences and humanities), practitioners (such as place holders, ceremony leaders, psychologists) and harm reduction and addiction and substance abuse experts, the workshop used the format of Open Space Technology. In spite of its high tech name this technique provides a pleasantly analogue and hands-on way to collect ideas, to select and focus and to collaborate in interdisciplinary teams on the agenda that was by and large determined by the participants. It was quite amazing to see how an empty wall for ideas and topics, soon transformed into a beehive of themes to discuss and evaluate. In breakout rooms these topics were discussed, according to the principle that it is okay to hop from one room to the next like bumble bees who can cross pollinate or like butterflies who can more silently absorb and transmit information at a later stage. The outcomes were synthesized using the reporting sheets from each discussion group, that were made available to all participants after the workshop.

Everything Else Matters: Film, Experiential Workshops, the Sea and Ruigoord

The workshop also included some plenary moments, such as the presentation of the findings from the Delphi study on setting conducted by the Centre for Psychedelic Research at Imperial College in London by Chloe Provoost-Morgan and Leor Roseman. We also engaged in a  presentation of the work-in-progress of the documentary on set and setting Everything Else Matters, a film co-commissioned by the OPEN foundation.Directors Kristina Kulakova, and producer Dmitry Repin presented and discussed excerpts from the film, interviewed several participants and actively worked on the film that will be presented at ICPR 2024. Ido Hartogsohn, assistant professor at Bar-Ilan University, gave a passionate keynote lecture, in which he proposed to extend the notion of set and setting to include the socio-historical context in which psychedelic experiences take place as well. Harm reduction specialist from the Dutch Jelinek and Trimbos institute shared their view and knowledge on harm reduction and several scientists presented their research and experiences either in smaller groups or on posters. 

Over the course of the week the empty offices at the Lorentz Institute started to be taken over by buzzing sounds, passionate exchanges of ideas, but also music and movements in space. In the meantime, in several experiential workshops  the idea of set and setting was put into practice: this opened up new dimensions: a breath work workshop by Katrien Franken moved participants deeply; a music workshop by Arno Adelaars and Jan Frank transformed the university room into a ceremonial space and invited participants to improvise music during breaks; Rini Hartman gave a taste of a Sante Daimo set and setting; and Andre van der Braak demonstrated different meditation techniques. All these experiences were not only important demonstrations of set and setting but contributed to the exchange and development of new ideas on set and setting.

These experiential events are at least as important as the formal research and academic discussion on set and setting. Also the evening program included an experiential element. We watched a screening of Maartje Nevejans’ beautiful documentary Descending the Mountain, documenting the story of a psychedelic scientist and a Buddhist monk who develop a lifelong friendship, which was  followed by a Q&A with the director. We enjoyed a barbecue at the Dutch seaside that invited several participants to a spontaneous dive into the cool and dark water of the North Sea. On Thursday evening the group made a visit to the unique cultural green village (hidden in the Amsterdam Harbor) Ruigoord with a guided tour by one of its founders, Hans Plomp.  

And Now? Concrete Outcomes and follow-up

 Throughout the week different groups started to work on different concrete outcomes of all the encounters: one group initiated a joint white paper on substance, set and setting. Another group focused on the development of a conceptual model and theoretical framework that highlights the surplus value of bringing together the perspectives of different disciplines and practices. And a third collective started to work on concrete guidelines for different groups of practitioners and policy makers with a particular aim at harm reduction and care. In many discussions we had, it was clear that while sharing the exact same hypothesis about the necessity to bring together substance, set and setting, it was not always easy to create ways to truly collaborate in larger projects. But this is precisely where innovation is needed we should embrace complementarity and serial disciplinarity, where each discipline, according to its own method or practice, covers a part of the entire psychedelic spectrum which can then be brought together at different stages. 

While all groups are still working on concrete papers and guidelines, it was clear that the commitment of working together, sharing spaces and places, provided the foundation for the establishment of an interdisciplinary European research network for psychedelic research. We were also able to conceptualize and establish parameters of responsible and safe use of psychedelics in different contexts (medical, religious, recreational and other). Such guidelines can be implemented by policy makers and practitioners and are aimed towards providing concrete advice and recommendations related to risk reduction of psychedelic use. 

At the end of the week we had a closing circle, in which every participant shared their insights and experiences. It was heart-warming to learn how the workshop had been an invaluable experience for everyone involved. It is a unique situation to be able to devote a full week with experts for an open and free debate about set and setting. And we sincerely hope that the participants will carry this positive afterglow forward in their own work and practice!  

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_{Reported by Patricia Pisters & Michiel van Elk (Board members OPEN Foundation)}

Let’s wear our preclinical researcher’s hats for a minute and suppose we forget about the BDNF receptors, intracellular 5-HT2ARs, and the reopening of critical periods. In that case, one thing is clear about classic psychedelics: neuronal surface 5-HT2ARs are the doors of hallucinations (mandatory note to the NMDA and KOR friends: we are talking about classic psychedelics here). Welp… guess what! The story is not that simple!

It has long been known that serotonergic -classic- psychedelics activate both Gq/11 and β-arrestin2 signaling upon 5-HT2AR binding, and even though non-psychedelic 5-HT2AR biased agonists already exist -or so was thought before the first Tabernanthalog trip reports started contradicting Olson Lab’s claims-, the role of these pathways in the psychedelic effects is unclear. There is no adequate pharmacological explanation accounting for the nature of the signaling mechanisms of these non-psychedelic 5-HT2AR agonists.

To dig deeper into their biology, researchers from Saint Joseph’s University, UCSD, and Medical College of Wisconsin developed a series of 5-HT2AR-selective ligands with varying Gq efficacies, including β-arrestin-biased agonists, and tried to predict their psychedelic potential using the head-twitch response in mice.

Among their findings, they observed that psychedelics exhibit fairly dynamic and time-dependent but similar profiles of Gq and β-arrestin activity. Moreover, 5-HT2A-β-arrestin2 recruitment efficacy is not a reliable predictor of potentially psychedelic molecules, while a threshold level of Gq activation is required to induce psychedelic-like effects.

But perhaps most importantly, their efforts in developing highly selective 5-HT2AR agonists yielded greatly insightful observations in terms of the relationship between drug structure modification and receptor binding profile. For example, attempts in reducing the electrostatic properties of the ring system in the phenethylamine scaffold (that is, drugs structurally similar to mescaline or 2-CB) substantially reduced 5-HT2CR and 5-HT2BR activity, but maintained potent 5-HT2AR activity, resulting in increased 5-HT2AR selectivity.

This study paves the way for the design of next-generation psychedelics with fine-tuned properties distinct from those of classical psychedelics, opening the possibility of tailoring their effects to the specific needs of the individual patient (or user).

Read the full publication here!

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_{Image credit: J. Kuhl}

When you enter the landscape of psychedelic-assisted therapy, there are two colloquial terms, or so-called extra-pharmacological (contextual) factors, that are deemed essential in preparation and facilitating therapeutic outcome. These are of course the ‘set’ and ‘setting’ that, respectively, broadly refer to how current-moment mindsets (expectations and intentions) and the environment are able to shape the psychedelic experience. But what about potential environmental influences from the past, a phenomenon also referred to as ‘imprinting’?

The phenomenon of imprinting is not entirely new and was recently brought to my attention during OPEN’s online panel discussion ‘Reality Check: Psychedelic Industrial Complex, Hype, Funding, and Research’ with Jane Hu, David Yaden, Josh Hardman, and Shayla Love. Somewhere halfway through the discussion, Shayla Love mentioned how the so-called ‘Brain-Reset’ mechanism of psychedelics was instantiated by the media, as one journalist picked this up by a participants’ report of how psychedelic-assisted therapy felt. It has since reverberated into the culture with many articles purporting this as an established mechanism of action of psychedelics and that in turn, according to Shayla, could influence (‘imprint’) expectations of participants in future clinical trials.

A recent study sought out to investigate whether imprinting has any kind of effects on therapeutic outcome. Accordingly, the study assessed a total of 26 previously recorded treatments sessions and phenomenological follow-up interviews from participants receiving ketamine for their treatment-resistant depression (TRD). In short, the acute experience of ketamine was significantly altered by digital media use prior to treatment and that higher levels of media exposure actually reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences. Below are summarized two typical examples of imprinting.

The first example consisted of a 28-year-old woman with TRD who reported that her ketamine experience was “hijacked” by Disney iconography. The study reports that this was influenced in particular by the observation that the participant spent up to six hours a day trading Disney pins on a social media forum prior to her treatment with ketamine. This diminished the amount of emotional and mystical content and greatly disappointed the individual. Yet, the participant did change her behavior because of this and ended up spending only one hour a day on social media and Disney pin trading. Notably, the participant posited that her insight in this kind of behavior was actually profound and lasting.

The second example concerns a 34-year-old man with TRD who summed up his ketamine experiences as “a pixelated consciousness” with videogame-like hallucinations, potentially due to the study’s observation that he played videogames for up to 16 hours a day. This was rather enjoyable for the participant, but he was also somewhat disappointed because it lacked any mystical or emotional content. The therapist and participant decided to cut down on videogame hours for the subsequent ketamine sessions and instead spent time with friends and family. Notably, this resulted in significantly different ketamine experiences that were more emotionally intense with marked feelings of grief related to past relationships. Most notably, the participant reported no more “pixelated consciousness.”

These findings corroborate and expand the extra-pharmacological model of psychedelic-assisted therapy, as imprinting seems to significantly influence the phenomenology and therapeutic outcome. The paper ends with a discussion on how imprinting is not the same as priming and suggestion, whether it is underrecognized or unimportant, if it is unique to ketamine or also applies to other psychedelics, various factors that could influence imprinting, dreams as a mechanistic model for imprinting, and how imprinting seems to be consistent with the relaxed beliefs under psychedelics (REBUS) model, and further clinical and scientific implications.

Read the full publication here!

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_{Image credit: ART IS AN EXPLOSION – stock.adobe.com}

Human beings of all cultures have been seeking altered states of consciousness (ASCs) since time immemorial. As a matter of fact, it has been posited by Ronal Siegel in his magnum opus Intoxication that our need to use mind-alter substances to induce ASCs has so much force and persistence that it functions almost like our drive for food, sleep, and sex.

In recent years, the therapeutic use of ASCs has become increasingly relevant in the treatment of various psychiatric disorders, thanks in part to the psychedelic renaissance. The phenomenology of psychedelics has often been compared to other ASC methods that do not require the ingestion of mind-altering substances, such as meditation, but also hypnosis. Yet, no study to date has made a direct comparison of these when it comes to their so-called ‘neural correlates’, which generally refers to the neural representation of a subjective experience. A recent study sought to address this knowledge gap in the literature by comparing resting state functional connectivity of psilocybin, LSD, meditation, and hypnosis in order to establish the neural correlates of each ASC method.

One of the most striking results of the study is that there was no common network in all four ASC methods, despite their significant phenomenological overlap. Perhaps this is due to the prominence of ineffability that is an inextricable part of ASCs, something that ultimately hints towards the fallibility of human self-report. Furthermore, the study shows that the direct comparison between hypnosis and meditation is associated with significant differences in functional connectivity and also differ when both of them are directly compared to either psilocybin or LSD. A final finding of the study, which might come as no surprise to some of you readers, is that psilocybin and LSD show no differences in functional connectivity when directly compared to each other. However, some results also suggest that they do show distinct relationships between their respective behavioral and neural correlates. In other words, this indicates that there are some discrepancies between the neural representation and what someone experiences subjectively when comparing psilocybin and LSD.

Overall, the authors conclude that the current results extend our understanding of the underlying mechanisms of ASCs. Most importantly, it highlights the clinical importance of investigating how ASCs can be utilized most effectively in the treatment of psychiatric disorders. Even though the current study looked at the acute effects of ASCs, there is increasing evidence that these are necessary for their enduring therapeutic effects. Although some researchers like Dr. David Olson argue to the contrary, a recent study caught my eye that further corroborates this view. Specifically, it demonstrated significant antidepressant effects two weeks following psilocybin that were correlated with increases in theta power,  an effect that is similarly observed following the practice of meditation and is accompanied by feelings of peace or blissfulness and low thought content.

But I digress… Ultimately, if we want to increase the efficacy of psychedelic-assisted therapy, the authors argue that it is of vital importance to understand the relationship between the acute effects of ASCs and the enduring therapeutic response given the observation that there is substantial variability in the acute response in psychedelics and that this acute experience can be shaped according to an individual’s set, setting, and dose. Accordingly, it is important to establish the acute neural correlates of various ASC methods in healthy controls, as it could contribute to the development of clinical biomarkers and map specific mechanisms of action to either a disease area or individual patient. Finally, given the observation that psilocybin, LSD, meditation, and hypnosis engage in distinct brain circuits, they could have potential synergistic properties that further facilitate the therapeutic response.

Read the full publication here!

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_{Image via Dall-E}

On June 23rd, 2023, the FDA made history in the psychedelics space by presenting its first-ever recommendations and considerations for executing clinical trials involving psychedelic drugs. With the growing popularity and research in this field, it’s a significant step forward in governmental institutions recognizing the potential of these substances. The FDA is currently collecting suggestions on the draft, which are possible to submit until August 25th.

Over the last two weeks, I’ve been reflecting on this topic and will use this article as an opportunity to share my personal thoughts.

What does the guidance contain, exactly?

The majority of the FDA’s guidance can be applicable to clinical trials of any therapeutics. However, the following considerations specifically pertain to psychedelic therapeutics:

• Investigational New Drug (IND) Application: Depending on the availability of sufficient toxicology data from prior clinical studies, some trials may be permitted without animal toxicology testing.
• 5-HT2B Receptor and Cardiac Effects: Special attention must be given to the impact of psychedelics on the heart and their binding affinity to the 5-HT2B receptor.
• Psychological Support: The evidence of psychological support contributing to psychedelic trials’ therapeutic outcomes was deemed limited by the FDA. Therefore, the inclusion of such support in the study design must be justified and quantified.
• Separation of Roles: To minimize bias, researchers providing integration sessions should be distinct from those involved in the dosing sessions.
• Blinding: The FDA suggests utilizing control groups that receive sub-perceptual psychedelic doses or drugs simulating certain aspects of the psychedelic experience to ensure blinding.
• Attendance: Two healthcare professionals, a lead and an assistant monitor, should be present during the trials.
• Study Duration: For most indications, the FDA recommends a 12-week evaluation period with follow-up assessments extending one year.

My Opinion: The Good

This month, there have been over 224 psychedelic studies, either live or currently recruiting patients. It is wonderful news that the FDA acknowledged the therapeutic potential of psychedelic-inspired compounds and saw it as more than a trend. By providing a framework for conducting clinical trials, the FDA aims to ensure rigorous scientific investigation into the safety, efficacy, and potential applications of these drugs.

The support of a governmental institution like the FDA could potentially accelerate the wider acceptance of psychedelics among the general public. It may also encourage other institutions to take proactive measures related to these compounds. This could involve taking action toward the establishment of accreditation methods for psychedelic therapists and microdosing coaches, the improvement of laws pertaining to the production and manufacturing of plant-based medicines, and the promotion of more relaxed regulations by governments regarding these substances.

My Opinion: The Bad

That being said, I do have some criticism of the draft. The FDA argues that combining psychedelics and psychotherapy makes for messy trials, to the point where any use of psychotherapy must be well-justified. This demonstrates a lack of consideration for the importance of setting and support structures in psychedelic healing. While many companies are developing drugs that are able to be taken without the support of a therapist, the majority continues to focus on compounds for psychedelic-assisted therapy, where the patient’s relationship with their therapist and the guidance received by them plays a crucial role in therapeutic outcomes.

I believe that the FDA’s concern with therapists may in turn lead to psychedelic pharmaceutical firms being driven more by company profits since a large cost driver (therapists) would be removed. I find this disappointing as the positive outcomes of psychedelic-assisted therapy were one of the main drivers of these compounds’ increased popularity, and there is a mountain of anecdotal and scientific evidence of its profound effect.

Another aspect I dislike is the recommendation to have a separate clinical for conducting integration and dosing sessions. This is not representative of real life, where relationship-building with a therapist is key for clients’ safety and outcomes. In practical terms, transferring information between the two practitioners would be time-consuming and may carry the risk of incomplete information transfer.

My last criticism regards the role of psychological support. The FDA recommends the presence of a lead monitor with a graduate degree and psychotherapy experience, and an assistant, with at least a bachelor’s and one year of mental health training. I agree with Chris Witowski, Co-founder of Psilera, who has mentioned in a Linkedin post that given the scale of the mental health problem, the assistant monitor requirement should be reduced, allowing for certifications alternative to formal education. A bachelor’s degree will not necessarily facilitate better care than a specialised training program in the field.

Conclusion

That being said, what is best about this situation is the amount of stakeholders that the FDA is engaging to optimize these guidelines. The organization is also collecting general feedback on the draft until August 25th. It is also important to note that while the FDA provides guidelines against which they will assess new drugs, they also understand that flexibility may be necessary to accommodate unique circumstances or innovative approaches. As the FDA continues to gather public input and refine the recommendations, it will be intriguing to witness the final version,

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_{Image via Dall-E}

Last week, OPEN executive director Joost Breeksema and OPEN board members Michiel van Elk and Patricia Pisters gave lectures during the second edition of the Summer School on Psychedelic Research in Groningen, the Netherlands. Close to 50 participants from around the globe attended the Summer School, which was co-organised by the Research School of Behavioural and Cognitive Neurosciences (BCN) of the University of Groningen, the University Medical Center Groningen (UMCG) and the OPEN Foundation.

Joost Breeksema spoke about the adverse effects of psychedelic use and offered an in-depth look at his qualitative research into the personal experiences of patients undergoing treatments with different psychedelics for severe mental disorders. Michiel van Elk shed light on the working mechanisms of psychedelics and the methodological challenges of psychedelic research during his two lectures. Patricia Pisters presented a fascinating analysis of aesthetics within psychedelic cinema.

Breeksema, who is also the coordinator of the Summer School on Psychedelic Research, looks back on a highly successful second edition: ‘It was magnificent. The Summer School has grown in size and grown in quality. We had such a wide variety of Netherlands-based researchers from multiple disciplines. There are so many different angles from which psychedelics can be studied. We brought all these different perspectives together.’

The Summer School welcomed students from a wide range of different academic disciplines and levels, from bachelor students to PhD candidates and postdocs. People traveled to Groningen from all over the world to take part: from China to Colombia, from Brazil to Australia and from differents parts of Europe to the US. Breeksema describes the Summer School week as ‘a sort of pressure cooker of learning, interacting and creating. Only something beautiful could come out of it.’

Next to an impressive amount of engaging lectures, the Summer School students were surprised with a diverse social programme, featuring an open-air yoga session, a cozy social hangout around a bonfire and a screening of the captivating documentary Descending the Mountain. One of the major highlights of the week, according to many, was a sacred cacao ceremony where the participants experienced a deep connection with themselves and each other. 

A wide range of topics within the field of psychedelic science and research was covered during the Summer School, including but not limited to: 

• Ketamine assisted psychotherapy for patients with trauma resistent depression (Jeanine Kamphuis, psychiatrist and researcher at the University Psychiatric Center in Groningen).

• The use of MDMA in PTSD treatment (Eric Vermetten, professor of medical-biological and psychiatric aspects of psychotrauma at the University of Leiden).

• Psychedelics and cognition (Stefanie Enriquez-Geppert, assistant professor at the department of clinical and developmental neuropsychology at the University of Groningen).

• Microdosing psychedelics (Kim Kuypers, associate professor at the faculty of psychology and neuroscience at Maastricht University).

• The philosophy of psychedelics (Aidan Lyon, philosopher at the University of Amsterdam).

• Validity threats in psychedelic science (Eiko Fried, associate professor at the University of Leiden).

• Psychedelics in religious studies (André van der Braak, professor of comparative philosophy of religion at the VU Amsterdam). 

• Research dilemmas and transdiagnostic action (Robert Schoevers, professor of psychiatry at the University of Groningen, head of psychiatry at the UMCG and director of the Summer School on Psychedelic Research).

The indisputable success of the second edition of the Summer School on Psychedelic Research is best put into words by the participants themselves:

• ‘I realise that I had forgotten what it felt like to be truly enthralled with subject matter in a formal learning environment.’

• ‘A top-notch summer school that exceeded all my expectations.’

• ‘This week was absolutely amazing; it was such a privilege to connect with like-minded people. It really felt like a psychedelic experience!’

Want to attend the 2024 edition of the Summer School on Psychedelic Research? Follow the Summer School Instagram profile or keep an eye on the Summer School website for more information, which will be provided early next year. Of course, we will also keep you updated through the Open Minded newsletter.

When asked whether applicants should have prior knowledge on psychedelics, Breeksema says ‘You really don’t have to be an expert, but during the Summer School, you will definitely become one! There is so much to be learned.’

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_{Photo’s by Martin Spijker and Jeroen Neef}

The chronicles of the psychedelic renaissance continue as Ernst Kuipers responds to a recent report regarding psychedelics’ potential therapeutic use. The following article provides a brief recap of the past year and summarises Kuipers’ response that could provide a glimpse of what the future of psychedelic-assisted therapy and research in the Netherlands is going to look like.

Approximately one year ago, I wrote a piece about our Dutch Health Minister Ernst Kuipers and how he stated that the Netherlands should be at the forefront of psychedelic research. This response was exciting to me, to put it mildly, and something I did not expect because of the stigma surrounding psychedelics. In short, Kuipers seemed very thrilled and up to date regarding psychedelic-assisted therapy (PAT). Specifically, Kuipers was aware of the potential of PAT for treating various treatment-resistant psychiatric disorders, while simultaneously maintaining a measured stance and acknowledging the various barriers that still persist today (e.g., lack of financial resources and therapy training).

Later that year on October 13^th, 2022, the therapeutic use of psychedelics was introduced to other members of the Dutch parliament. This happened during a roundtable discussion that was divided into four blocks and consisted of patient perspectives with PAT, the most recent scientific findings, stories from several therapists, and future perspectives for this novel treatment. At that time, I believed this was going to be a pivotal and historic moment for psychedelics and tried to watch most of the livestream whilst being in the midst of my own research that day. When tuning in, I was both relieved and elated when I heard one of the politicians saying: “I don’t know about the rest of you, but I find this extremely interesting!” Across the political spectrum, the Dutch parliament was excited about recent developments regarding PAT.

This brings us to the aforementioned report written by OPEN executive director Joost Breeksema, professor of psychiatry Robert Schoevers, and neuroscientist Rutger Boesjes. This report was presented to Kuipers on March 6^th, 2023, during a mini symposium at the University Medical Centre of Groningen (UMCG). In an earlier blog post, I wrote about how the report was aimed at further informing the Dutch Health minister regarding the current state of affairs of PAT.

And now, on June 26^th, 2023, Kuipers has written his official response towards the Dutch parliament in which he first and foremost “would like to thank ZonMw and the authors for the report that explores the opportunities, challenges, and health care innovation of psychedelic-assisted therapy for treatment-resistant psychiatric disorders.” In particular, these include the use of various psychedelics as psilocybin or ketamine for chronic depression or addiction, the use of MDMA for post-traumatic stress disorder, but also the use of LSD for cluster headache. Kuipers: “This report entails the first overview of the current state of affairs of PAT in the Netherlands and provides a significant contribution to the conversation about PAT and decisions about future steps.”

After proving a summary of the earlier report, Kuipers agrees with the authors and remains “positive about the development of PAT and its use in the treatment of severe or treatment-resistant psychiatric disorders.” He further states that “the development of psychedelics as treatment needs to be considered as the development of a medicine and should thus adhere to applicable guidelines.” Put simply, this means conducting the necessary clinical trials that are required to get a market registration for psychedelics. To pull this off requires a tremendous amount of effort and teamwork, which is why Kuipers “encourages various university medical centres and special health care facilities to engage in a national collaboration that allows for the coordination of the necessary research and gathering of information regarding quality, efficacy, and safety of PAT. I am exploring possibilities for financing a multiple year research program, potentially with a collaboration between the public and private sector.” 

Yet, this team effort also requires attenuating the various barriers associated with conducting psychedelic research. This includes the fact that psychedelics are illegal according to the so-called Dutch ‘Opiumwet’ that follows similar classifications of psychoactive substances as the United States Drug Enforcement Agency. For example, MDMA is listed as having no currently accepted medical use, despite its huge promise in the treatment of post-traumatic stress disorder when given with psychotherapeutic support. Furthermore, Kuipers states from the UMCG report that “researchers are concerned about political and societal acceptance when considering psychedelics as a potential medicine”, but also about “the increase in media attention towards PAT that can lead to non-medical use in society.” Indeed, it is important to remember that psychedelics are able to cause harm, particularly when given in an uncontrolled setting without any support. I highly recommend Jules Evans’ Challenging Psychedelic Experiences Project that focuses on psychedelic risk and harm reduction. Evans recently joined us for a live online event ‘Extended Difficulties After Trips, and What Helps People Deal with Them’ talk more about this and can be rewatched on our Circle community platform.

Another topic that is addressed in Kuipers’ letter is the compassionate use of psychedelics. This is a situation in which patients with a terminal illness or chronic disease have exhausted all current proven and available treatment options. Because these people are in dire straits, they are able to ask for early access to investigational drugs, including psychedelic substances as psilocybin or LSD. This could outweigh the expected value of routine care, palliative care, or no care at all, with the addition of assessing the expected value of PAT. Kuipers mentions that “compassionate use can be requested through the CBG (College ter Beoordeling van Geneesmiddelen)” – a Dutch independent authority that assesses the quality, effects, and safety of various medications in order to adequately inform the patient.

Although Kuipers mentions that “compassionate use is on the horizon”, he also says that “it might be untenable in the current phase, considering there is no clarity regarding market registration.” This is consistent with the UMCG report, where Breeksema and his colleagues stated that compassionate use is dependent on how PAT is going to be implemented within a therapeutic context.

Other questions according to Kuipers remain. Who is going to pay for psychedelics? Who is going to produce psychedelics? And what about paying therapists and clinicians for their treatment hours before, during, and after the dosing session? For scheduled substances, such as psychedelics, Kuipers emphasises that “there needs to be a location for the industry in the Netherlands, and this is currently not the case.”

Currently, the Dutch ministry of Health, Welfare, and Sport is frequently in contact with researchers and mental health care institutions to provide an advisory and faciliatory role. In addition, organisations as CBG can advise parties about the necessary steps towards market registration and provide advice about possibilities for compassionate use. Kuipers further mentions how other organisations, such as the Dutch ‘Care Institute’ (Zorginstituut), expertise centre FAST, and patient organisations, could further assist in conducting research and the ultimate implementation of PAT (e.g., insurance reimbursements and patient perspectives).

Kuipers mentions that this also includes the European Medicine Agency (EMA) – a decentralised agency of the European Union that is aimed at fostering scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health. In particular, Kuipers statest that “the EMA is actively involved in the subject and encourage researchers to ask for support when facing current challenges regarding recent development of PAT.” These challenges were recently published in The Lancetand the OPEN foundation hosted an online event with some of the paper’s authors, including Gitte Moos Knudsen, Marion Haberkamp, and Lionel Thelen. A recording of this event can be rewatched on our Circle platform.

Another notable recent development is the Platform for Psychedelics that has been launched within the Dutch Society for Psychiatry (NVvP). According to Kuipers, the “NVvP is an important party as it concerns itself with the advocacy of scientific and professional interests of psychiatrists and the advancement and stimulus of education and training in psychiatry.” Indeed, this is significant for PAT because the field still lacks an infrastructure for education. It is necessary for members of the NVvP and psychedelic researchers to come together to determine the next steps in developing education for PAT.

I think it is safe to say that psychedelics have now truly hit the mainstream. At the beginning of 2023, I watched an educational video about psychedelics from NOS – one of the biggest news and media outlets in the Netherlands – and only one month later I saw John Oliver do a sketch on his HBO show Last Week Tonight talk about the potential of PAT and mentioning documentaries as Fantastic Fungi and How to Change Your Mind. I highly recommend watching all of these videos and documentaries, because they are tremendously informative, funny, and very well produced.

In closing, however, I would want to emphasise here the following in accordance with the final words of Kuipers’ letter to the Dutch parliament: “the attention for psychedelics in the media has increased in recent years”, which has “created a hype with too high expectations regarding PAT.” Most notably, Kuipers refers to the UMCG report that illustrates how this hype has created the risk of self-experimentation in individuals with a severe psychiatric disorder that do not want, or cannot afford, to wait on market registration. This is why Kuipers favours the monitoring of potential increases in self-experimentation and incidences, and to explore possibilities of providing prevention, education, and harm reduction for the people that are, unfortunately, in dire straits.

List of ongoing studies in the Netherlands

Phase I:

N,N-dimethyltryptamine (DMT)

• Smoking addiction – Center for Human Drug Research

Phase II:

5-MeO-DMT (DMT)

• Treatment-resistant depression – UMCG

MDMA

• Post-traumatic stress disorder – ARQ Nationaal Psychotrauma Centrum and Maastricht University

LSD

• Low dose LSD for ADHD – Maastricht University
• Low dose LSD for chronic cluster headaches – Radboud UMC and Leiden UMC

Ketamine

• Demoralisation in cancer – UMCG
• Acute suicidality – UMCG
• S-ketamine for pain sensitivity in patients with fibromyalgia – LUMC

Psilocybine

• Low doses of psilocybin and ketamine for cognitive and emotional dysfunction in Parkinson – Maastricht University
• Pain in fybromyalgia – Maastricht University
• Neuropathic pain – Amsterdam UMC, LUMC en Antoni van Leeuwenhoek

Phase III

Ketamine

• Assessing S-ketamine compared to electroconvulsive therapy for severe depression – UMCG, ProPersona Nijmegen, Parnassia/PsyQ Den Haag and LUMC.

NOTE. Phase I concerns the safety and determining the dosage of a compound, phase II focuses on a small group of patients that are administered one dose to determine preliminary therapeutic efficacy, and phase III consists of a large group in which patients receive both a psychedelic substance and a placebo.

From April 20th to 22nd, 2023, Breaking Convention convened in Exeter, United Kingdom. A mix of psychonauts, researchers, and psychedelic curious gathered to discuss the latest research, showcase psychedelic art, and exchange views in this blossoming field.

Breaking Convention (BC) was kicked off by its four directors, Nikki Wyrd, Aimee Tollan, Hattie Wells, and Alexander Beiner. Each spoke to their journey as participants and organisers of the non-profit gathering. Beiner highlighted the importance of guarding how the mainstreaming of psychedelics is shaped. No doubt existed among 1100 participants (Breakeros) that in fact, psychedelics are going mainstream.

Wells pointed out that BC is a multi-disciplinary conference, one where perspectives from many angles merge together. She warned that Western clinical medicine shouldn’t forget the roots of psychedelic knowledge that run deep in indigenous knowledge. Wyrd compares the gathering to a mycelial network, one for which the fruiting bodies are nourished and spores will be spread out all over the world once the conference ends.

The science; presentations with a variety of perspectives

The quality of evidence presented at BC was notably diverse, reflecting the wide-ranging interests and expertise of the attendees. While some speakers reported on rigorous clinical trials, others opted to share personal experiences or case studies, providing a holistic view of the current state of psychedelic research. This mix of approaches allowed for a comprehensive and nuanced exploration of the field while highlighting the need for more standardized research methods.

The conference featured an impressive array of research topics, demonstrating the potential for psychedelics to address various mental health and addiction issues. From the use of ibogaine in treating addiction to the exploration of how psychedelics might be applied in the treatment of obsessive-compulsive disorder (OCD), the scope of inquiry was vast and inspiring. Although it is impossible to recap every talk individually, the striking diversity that sets this event apart from other conferences in the field is worth noting.

As psychedelics continue to gain mainstream attention, it was clear that the speakers at BC were aware of the hype surrounding these substances. Throughout the conference, a sense of caution and responsibility resonated among participants, emphasising the importance of conducting rigorous research and carefully considering the implications of psychedelic use in various contexts. The conference fostered a thoughtful and grounded atmosphere by acknowledging this burgeoning field’s potential pitfalls and challenges.

The culture; a psychedelic farmers market, VR headsets, and art installations

The cultural aspect of BC was a vibrant and engaging reflection of the diversity within the psychedelic community. Attendees were treated to a unique “psychedelic farmers market,” where an array of stands offered mushroom-infused chocolates, eco-conscious decals, and a wealth of psychedelic literature. Additionally, harm-reduction societies and various NGOs showcased their work, providing valuable resources and fostering connections among conference-goers. This bustling marketplace served as a hub of creativity and exchange, demonstrating the wide range of interests and pursuits within the psychedelic sphere.

Technology also played a role in the cultural experience at BC, with several virtual reality (VR) setups available for attendees to explore. These immersive installations featured psychedelic-inspired games, offering participants a brief escape from the conference environment and transporting them into otherworldly realms. The VR experiences provided a unique opportunity to delve into the intersection of technology and altered states of consciousness, illustrating the potential for innovative applications in the future of psychedelics.

Art installations were another highlight of the conference, with various engaging and interactive pieces on display throughout the three-day event. These immersive exhibits offered attendees the chance to experience the creative expressions of the psychedelic community, sparking conversation and inspiring reflection.

In addition to the rich program of scientific talks, on Friday and Saturday there was an opportunity to attend workshops. These ranged widely in focus, from techniques in psychedelic-assisted therapy and the integration of music and technology in these practices, to various workshops centred around ritual, nature and healing, and embodiment. What stood out was the open and unreserved attitude of the workshop attendees, leading to a freedom of self-expression in the groups and opening the door for an immersive experience. 

On Friday night, in a candle-lit live cinema performance, Vincent Moon showcased and soundmixed footage of musical gatherings from various cultures and religions from around the world, in a celebration of the common humanity in ritual, meaning, and tribe. 

The vibes; undoubtedly psychedelic with a sprinkle of sobriety

BC was infused with an unmistakable psychedelic atmosphere, yet it also maintained a strong sense of sobriety and realism. Presenters openly acknowledged the challenges and complexities associated with psychedelic research and application. Issues such as blinding in clinical trials, scaling up treatment options, the absence of support services, and the ongoing criminalization of users were brought to the forefront, demonstrating a commitment to addressing these concerns head-on and fostering an environment of honest discussion.

A common thread among many presenters was their personal experience with the transformative potential of psychedelics. While they shared stories of these substances’ positive impact on their lives, they were also candid about the risks and potential downsides associated with their use. This balanced approach allowed for a more comprehensive understanding of the psychedelic landscape, highlighting its promise and pitfalls.

Despite the serious nature of many talks, Breaking Convention 2023 also provided ample opportunities for connection and camaraderie. Spontaneous hugs, joyful reunions, and stimulating conversations were commonplace at the conference and informal gatherings in local pubs and on the dancefloor. The event cultivated a sense of community and shared passion, showcasing the unique blend of dedication, enthusiasm, and open-heartedness that characterizes the psychedelic movement.

The Dutch Government establishes a state commission to investigate the risks and benefits of MDMA, including its potential medical use. The commission will study the impact of MDMA on individuals, society, and public health. Additionally, the commission will examine the advantages and disadvantages of potential medical applications of MDMA. 

According to Dutch Minister of Health, Ernst Kuipers, there are good indications that the use of MDMA can help patients in specific situations where conventional forms of therapy cannot. Recently, the minister received a report from ZonMW (the Dutch organisation that subsidises scientific research to develop and innovate healthcare) about the therapeutic applications of psychedelics in the Netherlands.

The state commission will also assess the European legal context and relevant treaties related to MDMA use. This comprehensive review of MDMA’s status and potential therapeutic applications will provide valuable insights that should inform future drug policies and decisions related to psychedelic assisted psychotherapy in the Netherlands.

It’s worth noting that the state commission is an independent, ad hoc advisory body that functions autonomously from any Ministry. This means that the commission will operate with impartiality and objectivity, providing unbiased insights and recommendations to the Council of Ministers. State commissions in the Netherlands usually investigate a wide range of topics, including the functioning of the parliamentary system and democracy, euthanasia and institutional discrimination.

The commission, which includes experts in various fields such as the treatment of psychotraumas, criminology, and addiction care, aims to provide the cabinet with its conclusions and advice by January 2024.

We eagerly await the commission’s findings and recommendations. Stay tuned for updates on this important development as we continue to follow this issue closely.