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Farewell Letter to OPEN

After 15 years, Dorien Tatalas says goodbye

22-02-2022

After 15 years of service, I recently resigned from the board of the OPEN Foundation. In these words of goodbye, I’d like to share some personal reflections on the foundation’s (and to some extent, my own) journey into adulthood, as well as some of my hopes for the future. 

Magic Carpet Ride

In 2006 I was a psychedelically inquisitive cultural anthropology student, looking for her tribe. I longed for connection with others who were personally and academically curious about psychedelics and the states of consciousness they give us access to. The legendary LSD Symposium in Basel opened my eyes to the existence of a community of sciency psychonauts and I wanted to be part of it. Since the Netherlands lacked an organization that combined science and psychedelics, I did what young and naive idealists do: I decided to start a new organization. Little did I know that this foundation would become so intertwined with my life and identity, on so many levels. If psychedelics are the red thread in all of my adult life, OPEN is a delicately woven magic carpet – and I’m immensely grateful for the ride. It has brought me to new places, new ideas, and aspirations and it connected me with so many like-minded people, who over the years have become my colleagues, friends, and advisers. I even met my significant other – yes, OPEN has quite literally led me to my family. 

OPEN’s Journey

We started out as a local student-run organization with many dedicated and loyal volunteers. The taboo on the topic of psychedelics was still palpable, even in a country with a supposedly progressive drug policy like the Netherlands. To give an example: when OPEN wanted to become a customer at a national sustainable bank in 2007, we were denied a bank account because the topic of psychedelics was deemed too controversial – even in the context of academic research. How much has changed since those early days.

Over the past decade, OPEN has developed into a mature organization with an official tax-deductible non-profit status. If our foundation excelled in one thing, it’s in organizing conferences: the Interdisciplinary Conference on Psychedelic Research (ICPR) has become an internationally renowned event praised for its high academic quality. When we organized our first lecture in 2007 – “Ayahuasca & Anthropology” with Jeremy Narby – we could only fantasize about a psychedelic conference with accreditation for Dutch mental healthcare professionals. At ICPR 2016 this fantasy became a reality and ever since, our conference has been officially accredited by the leading professional mental healthcare organizations. 

Some of OPEN’s recent achievements that I’m proud of are the 2020 publication of the “Tijdschrift voor Psychiatrie” (the leading Dutch journal for psychiatrists) which was dedicated entirely to psychedelics; the ongoing collaboration with the KNAW (Royal Dutch Academy of Sciences) which so far has resulted in a several very interesting symposia; and the very recent manifest “Therapeutic use of Psychedelics” which has opened up a constructive dialogue with the Dutch Ministry of Public Health about the regulation of psychedelics assisted therapy. All of the above are examples of collaborative efforts and they illustrate one of OPEN’s core qualities: its ability to connect people and organizations, to build bridges between academic and professional fields. I haste to add that my felt pride in these achievements is purely from the sideline, as a board member – I haven’t been actively involved in any executive tasks for quite a long time. Full credits and gratitude for these achievements go to all of OPEN’s executive employees and the team of dedicated volunteers.

Exciting Times, New Challenges

As a network organization in the psychedelic field, OPEN is witnessing a huge change in the professional climate. Psychedelics are now being hailed as “the new promise in mental healthcare” by professionals from a multitude of backgrounds, as well as by mainstream media and multi-billion investors. The psychedelic renaissance has definitely shifted gears – and although these times are definitely exciting, they also come with challenges.

Commodification

One of the challenges that non-profit organizations like OPEN currently face, is how to relate to and navigate in an increasingly complex field, that includes stakeholders whose interests in psychedelics are mainly economical. What’s at stake in the rapidly commodifying field of psychedelics are, among others, safety and equal access. Such topics involve exploring ethical questions  – the answers to which will reverberate in the ways in which psychedelics will be integrated into our healthcare systems and societies. If you ask me, answering these far-reaching ethical questions should not be left to the market. Solving these complex issues is not the prerogative of the academic world either. The future of psychedelics now belong to a – primarily local, but increasingly global –  public debate, in which non-profit organizations in the psychedelic domain are contributing their independent, evidence-based, and objective voice.

Diversity

Another issue that I take at heart, which I hope OPEN will address within its own organization and events in the coming years, is the matter of equal representation and diversity. The psychedelic research world in 2022 is still primarily a white, middle/upper class, heterosexual, cisgender, male-dominated domain. Other ‘flavors’ of being human are painfully underrepresented or lacking entirely – not only as presenters at conferences but also as participants in psychedelic research and members of (advisory) boards. Alas, OPEN is no exception –  there is certainly room for improvement to diversify our board, advisory board as well as presenters at ICPR. Our very diverse base of volunteers does look very promising in this regard and hopefully will inspire other segments of the organization.

For a topic so rich and colorful as psychedelics, that pertains to a universal human experience, the lack of diversity is not only an embarrassing fact but such a missed opportunity. We are all biologically wired to experience psychedelic states of consciousness – but how we experience these states subjectively, how we reflect upon and interpret them, how we give meaning to them… how can this not be influenced by our subjective experience of ourselves and our relation to the world? Time and time again, it is stressed that set and setting are paramount in determining the psychedelic experience. Let’s not forget that gender, cultural background, ethnicity,  socioeconomic status (among others) are all part of that set. Diversity is a rich palette of all the different hues of human experience – if there’s one research area that can’t get away with using greyscale only, it’s psychedelic research. 

Precious Jewel

As my concluding thoughts, I want to build on a well-known metaphor of psychedelics as a multi-faceted diamond. In contemporary western societies, psychedelics have long been a diamond in the rough, valued for their potential by a relatively small group of people. They have been polishing the gemstone by using the scientific method, and by doing so, are attracting more and more people who, for various reasons, are interested in this jewel. Although psychedelics are being hailed as a promising tool in medicine, it’s important to emphasize that clinical research into these substances is just one of the diamond’s many facets. Psychedelics and the states they induce are such a rich and complex research subject – to study them from one discipline only wouldn’t do justice to it. The sociological, anthropological,  philosophical, neurobiological, and psychological perspectives – just to name a few – are all equally deserving of being studied. They are also intricately related to each other. By stimulating an interdisciplinary approach, organizations like OPEN contribute to the polishing of the entire diamond.

It’s worth noting here that many non-western cultural traditions have appreciated the richness of psychedelic consciousness for centuries and that there is a lot to be learned from such traditions – even if they take an angle that at first glance doesn’t seem compatible with our materialist scientific approach. The reverence and respect with which they treat psychedelic agents are exemplary and there is much wisdom in the ritual infrastructure in which psychedelic journeys are embedded in their societies.

As the academic world at large is becoming increasingly attracted to the precious gemstone called psychedelics, so are other domains of our society drawn to its shimmer and shine. The resulting tension raises fundamental questions, a few of which I will leave you with to consider. If all humans are biologically wired to get a glimpse of this diamond – can it ever be claimed as someone’s property? Will this diamond divide us, once again? Or does its true power lie in its ability to connect us?

Thank You & Fare Well

On this note, I would like to say goodbye. I wish OPEN all the best – may you continue to connect people, organizations, and the many different academic disciplines from which psychedelics can be studied. May you show the academic world what a fascinating diamond the psychedelic state of consciousness is while maintaining an objective and independent voice.

A huge thank you to everyone who has been involved with OPEN in the past 15 years – and a prospective word of appreciation for all of the foundation’s future supporters. 

Farewell, dear OPEN Foundation! I will happily take a seat in the audience at ICPR 2022. Or… perhaps I will apply as a volunteer!)

Yours truly,

Dorien Tatalas

Co-founder, former Chairwoman & former board member of the OPEN Foundation

With my dear friends and (former) board members of OPEN, at the first ICPR in 2012

Treating drug addiction with psychedelics looks promising

Although controversial only a few years ago, there is ample evidence that psychedelics can help in the fight against addictions (use disorders). Over the past decades, there have been multiple studies looking into the workings of psychedelics in the field of addiction. Multiple trials have concluded that there are indeed possibilities to develop psychedelic-assisted treatments towards treating multiple drug addictions. Below we list just a few promising areas which include LSD for alcoholism, psilocybin for smoking cessation and alcoholism, and ibogaine for opioid addiction.
Back at ICPR2012, researchers from Norway presented a meta-analysis of randomized controlled trials using lysergic acid diethylamide (LSD) for alcoholism. Researchers Krebs and Johansen had found six trials done in the 1960s and 1970s that included a total of 536 participants. The researchers concluded that “A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.” The results of the meta-analysis were published in the Journal of Psychopharmacology that same year and made it to mainstream media.
Contemporary addiction research has focused on using two compounds in particular: psilocybin and ibogaine. LSD is less researched, perhaps because of stigma or the long active duration of the psychedelic effects of LSD. Ketamine and MDMA are also researched and covered in this year’s online conference. Preliminary studies suggest that these compounds may help with the treatment of drug-related disorders. However, it is still not completely clear how their mechanism of action results in the observed outcomes.
At Johns Hopkins School of Medicine, Professor Matthew Johnson conducted a study with psilocybin and tobacco smokers. Twelve of the 15 participants managed to quit tobacco smoking, and importantly: maintained their decision to quit. Although it was a small sample group, a success rate of 80% was enough to warrant studies with larger groups.

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Johnson, who is currently the President-Elect of the International Society for Research on Psychedelics, will give a talk at our Psychedelics in Psychiatry and Psychotherapy Symposium on the working mechanisms of psychedelics used in clinical research.

What could be the mechanism of action that helps people kick their addiction when treated with psychedelics? I an interview we did with Prof. Johnson in 2015 he stated that: “evidence suggests that there are psychological mechanisms of action at play. For example, people endorse that after the psilocybin sessions, it was easier for them to make decisions that were in their long-term best interest, and they were less likely to make decisions based on short-term, hedonistic desires.” They also seemed to feel more in control of decisions about their behavior, and Johnson says “they also reported an increase in their self-efficacy, their confidence in their ability to remain quit.”
Another area where psilocybin seems promising is in treating alcoholism. Addiction researcher Michael Bogenschutz at New York University has been interested in alcohol-related treatments and is now conducting studies using psilocybin: “I’m interested in addiction in general but for me alcohol, which is a very common, devastating addiction throughout the world, was a logical place to start. As I learned when I started investigating the topic, a considerable amount of research on the use of psychedelic treatment (mainly LSD) and alcohol had already been conducted in the late 1950s.”

Elizabeth M. Nielson, PhD, CASAC - Psychedelic.Support
At ICPR2020 Dr. Elisabeth Nielson will present the historical context and current clinical research on Psilocybin-Assisted Treatment of Alcohol Use Disorder.
In addition, at the upcoming International Symposium on Psychedelics in Psychiatry and Psychotherapy (ISPPP) there are several presentations about clinical application for psychedelics in alcoholism, including the Bristol Imperial MDMA in Alcoholism Study (BIMA) which is an open label within-subject feasibility study in 20 patients with Alcohol Use Disorder who have recently undergone detoxification. The study is conducted by Ben Sessa, MD, one of the ICPR2020 speakers, and its principal investigator is Professor David Nutt.

A less known psychedelic compared to psilocybin and MDMA is ibogaine, which is derived from the African plant Tabernanthe iboga. Ibogaine was a hot topic at this year’s World Economic Forum which included positive reports on ibogaine’s potential role as an addiction interrupter for opioid addiction.
In the Netherlands, researchers at the Radboud University have been investigating the use of ibogaine for addiction. During ICPR2016, researchers from Radboud shared some promising pre-clinical evidence for the efficacy of ibogaine in treating addiction and shared some of the challenges of conducting psychedelic research in the Netherlands.
Currently there are several clinical research projects recruiting participants for psychedelic research in the Netherlands and Europe.
Luís Fernando Tófoli, who is a Professor of Psychiatry at the Faculty of Medical Sciences of the University of Campinas, Brazil, gave a fascinating review at ICPR2016 about brain imaging studies on psychedelics and their relation to addiction studies. Reviewed results point to effects in the medial prefrontal cortex, the anterior and posterior cingulate cortex and the precuneus. Psychedelics also seem to affect limbic structures (e.g. amygdala), insula, occipital lobe and, less frequently, thalamus and they have been associated with a deactivation of the default mode network. Psychedelics have a relatively modest impact on dopaminergic circuits associated with addiction, but they affect structures implicated in cue processing and decision-making in drug-seeking behavior.
At ICPR2020, Prof. Tófoli is returning, this time discussing the role of integration in psychedelic experiences, including in the treatment of addiction with ibogaine in biomedical clinics.

What is the future of legal MDMA?

There has been a renaissance in the research of psychedelics, and much of it has been led by promising studies over the past two or three decades. Aside from the discussion of whether MDMA is a true ‘psychedelic’, it is clear that recent studies have created momentum to reconsider these substances as medication for severe mental health problems such as depression, anxiety or addiction.
MDMA’s application to trauma therapy has become one of the central priorities of psychedelic researchers. So what is the current state of knowledge and where do we stand in the regulatory process? According to MAPS-founder Rick Doblin, MDMA will be legal soon if the hard work continues. “I keep saying it’s going to be 2035”.
MDMA Treatment
Victims of war or sexual assault are prone to develop anxiety and avoidance behaviors as a result of these tragic experiences. Some of them may be diagnosed with Post-Traumatic Stress Disorder (PTSD), a condition characterized by severe feelings of fear and distress in response to trauma-related details. The increasing prevalence of PTSD is aggravated by the lack of treatment options.
Current trauma-focused psychotherapies, such as exposure and cognitive-behavioral therapy, have important problems of access for certain high-risk populations, as well as high dropout rates. In regard to efficacy, some reviews have found that up to 70% of patients retain their PTSD diagnosis after treatment.
The only two pharmaceuticals with FDA approval also seem to be inefficient for many. One third of all PTSD patients are estimated to be treatment-resistant. This diagnosis is given when several different treatments fail to improve symptoms.

MDMA trials have focused on this specific population because of strategic reasons. It is easier to get permission to test a new drug on patients for whom everything else has failed. Psilocybin trials have taken a similar approach by focusing on treatment-resistant depression or anxiety related to the end of life.
Current clinical research employs a hybrid treatment model that combines the administration of 75 to 125mg of MDMA with therapeutic support provided in preparation and integration sessions. During the drug sessions, therapists monitor the patient and adopt a non-directive approach that allows the person under the effects of MDMA to dive into the experience with minimal interruptions. This model of psychedelic-assisted psychotherapy entails a groundbreaking paradigm in psychiatry that goes beyond mere medications and talk therapy.
A long path
It has taken a while before these modern trials were set up. MDMA is an amphetamine derivative first synthesized by Merck Laboratories in 1912 and later rediscovered by chemist Sasha Shulgin in the 1970s. At the time, psycholytic therapy was being developed with LSD and psychiatrists saw a new potential tool for psychotherapy in MDMA and its empathogenic properties.
Unfortunately, the increasing popularity of “Ecstasy” in recreational contexts and the ensuing anti-drug propaganda soon led to the classification of MDMA as a Schedule 1 substance in 1986, which introduced immense obstacles to scientists investigating its medicinal application.
Ever since, the Multidisciplinary Association for Psychedelic Studies has been working for the approval of MDMA as a therapeutic treatment in mental health and to remove the immense barriers that were thrown up for the potential medication.
Although preliminary investigations by Charles Grob had successfully proved the safety of administration of MDMA to healthy subjects in the 1990s, the first MAPS-sponsored trial for PTSD conducted in Spain by José Carlos Bouso was shut down because of political pressure from the Spanish authorities.
Placebo challenges
So far, six phase-2 clinical trials have been completed, and despite the small samples and the methodological limitations, the results are very promising. The first randomized controlled trials with PTSD patients began to take place in the late 2000s, and resulted in a landmark paper from 2011 by Michael Mithoefer, Mark Wagner, Ann Mithoefer, Lisa Jerome, and Rick Doblin. It concluded that ‘the rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group’.
One year later, most of these patients for whom all other treatments had failed still showed a persistent and significant improvement. More importantly, the lack of serious adverse effects pointed at the safety of MDMA in a clinical context and paved the way for more trials.

Skeptics pointed at the methodological weaknesses of this first trial. They criticized the use of lactose as placebo and the difficulties to blind the effects of MDMA to patients and investigators, a common problem in psychedelic therapy trials. An attempt of replication in Switzerland by Peter Oehen which circumvented the blinding problem with an active placebo group (25mg MDMA) showed good results, but were not statistically significant.
Researchers suspected that differences in the work and style of the Swiss therapists might have been behind these suboptimal results, which raised the question of how to standardize the psychotherapeutic part of the treatment. In subsequent trials, MAPS developed an adherence rating system in order to ensure that therapists stick to the standard guidelines of their therapeutic model.
In 2018, Michael Mithoefer published the first dose-response study, which compared the efficacy of three different doses of MDMA: 30mg, 75mg and 125mg. The groups with middle and high doses showed significant remission of PTSD with respectively 86% and 58% of each group’s sample not meeting the diagnostic criteria anymore after treatment, improvements which persisted in the one year follow-up. Shortly after, a similar study by Marcela Ot’alora replicated the results with 76% of patients not meeting the diagnostic criteria for PTSD one year after the treatment.
A Path Towards Regulation
Given these promising results, the FDA accelerated the approval process of MDMA with the Breakthrough Therapy designation in 2017 and allowed the early compassionate use of MDMA-assisted psychotherapy for treatment-resistant patients in 2020.
Two ongoing multi-site phase-3 trials sponsored by MAPS are currently assessing the efficacy of MDMA in around 200 participants from the US, Canada and Israel. Recently, MAPS’ interim analysis of the first phase-3 trial suggested that their results will probably reach statistical significance, and if nothing goes wrong, MDMA could be approved for the treatment of PTSD by mid-2022.
In the meantime, more phase-2 trials are starting to take place in Europe for PTSD and other conditions such as alcoholism. With the first psychedelic substance on the verge of approval, many questions remain in the air:

All these questions will require years of additional research, which needs to be done by current and future doctors, researchers and policy makers. But the direction and ambition of all this research is clear: to turn the hard facts of well-researched trials into a regulatory model, so that MDMA will be a legal future medication to help many.

What microdosing did for the perception of psychedelics

Over the past decade, the phenomenon of ‘microdosing’ has had outsized implications for the perception of psychedelics. Before this phenomenon, narratives around psychedelics always assumed a large dose and a full psychedelic experience. After the popularization of the concept of microdosing, the idea that psychedelics could be taken in small quantities -as a cognitive enhancer- became more prevalent and accepted. Ever since, they’ve been hailed as valuable tools for enhancing various aspects of cognition, creativity, emotion and neuroplasticity.
This article takes notes from Aleksi Hupli’s upcoming PhD dissertation in Sociology at the University of Tampere called: Smarter with Drugs. Cognitive enhancement drugs from users’ perspectives. In it, he partly explores why psychedelic microdosing should be included in the pharmacological neuroenhancement discussion and debate.
Albert Hofmann – the discoverer of the psychoactive properties of LSD – already mentioned in an interview with High Times in 1976 that “very small doses, perhaps 25 micrograms, could be useful as a euphoriant or antidepressant” (Horowitz 1976). The current renaissance of psychedelic microdosing research is usually accredited to Dr. James Fadiman, who dedicated a small chapter to describe experiences with “sub-perceptual doses” in The Psychedelic Explorer’s Guide, published in 2011. Prior to Fadiman, we have to go back to early research done in the 1950s and 60s – especially by the US military – on low doses of LSD. These studies were reviewed by another ICPR2020 speaker, Dr. Torsten Passie (MD) and partly republished in his book The Science of Microdosing Psychedelics (2019), arguably one of the most comprehensive publications on the issue of microdosing to date.
The “very small dose” of 25 micrograms mentioned by Hofmann is not technically considered a microdose or “sub-perceptual dose” as described by Fadiman (2011). As the “common” recreational dose of LSD ranges from 50 to 150 micrograms (Passie et al. 2008), and in contemporary clinical settings from 20 to 200 micrograms, it is still fairly unclear what a “microdose” really is compared to a very low dose or “minidose” (Kuypers et al. 2019; Passie 2019, p. 9-10). According to Fadiman, Hofmann called microdosing “an under-researched area” (Fadiman 2011, p. 211; see also Passie 2019, p. 23-25) and it did take over 45 years for the topic to be picked up by modern mainstream media and research.
Not accepted yet
Some psychedelic researchers remain sceptical about microdosing (e.g. Nichols, Roseman & Timmerman 2018, p. 83) while others acknowledge that “This role of psychedelics as cognitive enhancers is certainly an area in need of more research” (Sessa 2017, p. 276). It is important to note that ‘microdosing’ has several different meanings: for instance, in pharmacokinetic studies, microdosing is being used as a method in novel drug toxicology research. In addition, microdosing is also used as a novel technology in agriculture as a method of distributing plant nutrition (Passie 2019, p. 4).
Lack of research did not prevent a certain “media-hype” from developing, as there were plenty of media reports around the topic of microdosing. These reports described microdosing as a “Revolutionary Way of Using Psychedelics” (High Existence 2014) and, in a “brief history of microdosing” written by Vice in 2015, stated that “while the idea hasn’t yet catapulted itself into the mainstream, it’s getting there”. The following years indeed saw more mainstream media outlets writing about how LSD microdosing “became the hot new business trip” (Rolling Stone 2015) and “the new job enhancer” (Forbes 2015). Microdosing was affiliated with work productivity as a “new brain booster” (The Times 2017) especially in the technology hub Silicon Valley located in California (Wired 2016; Huffington Post 2017; also Mishra 2018; Hupli 2019). These media reports usually included mainly positive reports from people practicing or experimenting with psychedelic microdosing despite that for a long time there was indeed a lack of published research available, as still remains the case.
The definition on Microdosing
In their comprehensive overview of the current literature Kim Kuypers and colleagues, many of whom are presenting at ICPR2020, state: “the term ‘microdosing’ appears to consist of three components: 1) The use of a low dose below the perceptual threshold that does not impair ‘normal’ functioning of an individual. 2) A procedure that includes multiple dosing sessions. 3) The intention to improve well-being and enhance cognitive and/or emotional processes” (Kuypers et al. 2019). Thus, firstly, the dose should be low enough so it does not at least impair “normal” functioning, and in the publication the authors offer a table which includes varying doses (Microdose, Very low Dose, Low dose, Medium dose, High dose) of varying psychedelic compounds (psilocin, LSD, DMT and Ibogaine) that have been studied both in preclinical and clinical research. The authors write that “These doses are approximate values” which were presented as “Per kilogram dose values” which had been “converted to values for a 70-kg person” (Kuypers et al. 2019, p. 3), thus their applicability to ‘real-life settings’ requires careful consideration.
The second component of microdosing according to Kuypers et al., included a procedure with multiple dosing sessions for which there is no unified protocol. This multiple dosing of psychedelic compounds, which is something that usually does not take place with higher doses, is one of the issues that has raised concerns of potential cardiovascular risks associated with nearly daily activation of serotonin receptors with potent partial serotonergic agonists like LSD and psilocin (Kuypers et al. 2019;  Nichols, Roseman & Timmerman 2018, p. 83; Passie 2019). Kuypers et al. (2019, p. 8) conclude that “the possible effects and implications of microdosing remain largely unknown.” While online forums have a vast database of reported effects, from Youtube (Hupli et al. 2019a) to Reddit (Lea, Amada & Jungaberle 2019), according to Kuypers et al. (2019) “the true amount of active substance in these is unknown”. From a research and public health perspective this is, of course, problematic to say the least.
The third component of microdosing described by Kuypers et al., “having an intention to improve well-being and enhance cognitive and/or emotional processes”, is indeed something that users often seem to have when they practice psychedelic microdosing (e.g. Lea et al. 2020; Fadiman & Korb 2019; Hutten et al. 2019; Polito & Stevenson 2019). However, “while in these anecdotal reports the user deliberately ingests a substance for a reason, expecting positive effects, it is difficult to distinguish between expectation ‘placebo’ effects and the effect of a microdose.” (Kuypers et al. 2019, p. 8). From user’ perspectives, however, there is ‘an effect’, whether due to pharmacology or the excitement of doing some thing, even something illegal, but at least something that might improve one’s life-situation which is more than understandable.
Thus, this trend begs for more research on the topic to distinguish “the actual from the imaginary effects of microdosing” (Passie 2019, p. 46), not only for therapy but also for pharmacological neuroenhancement. According to a recent review of psychedelic microdosing, focusing specifically on its potential as a cognitive enhancer, Rifkin, Maraver and Colzato (2020, p. 9, italics added) “conclude that microdosing psychedelics is a promising means for enhancing various aspects of cognition, creativity, and emotion recognition, and that they may be valuable tools to augment cognitive flexibility and neuroplasticity.” However, they also acknowledge that “These findings imply that psychedelics should not be treated as a uniform class of drugs, particularly with respect to microdosing. Various psychedelics, with their distinct receptor affinities, will almost certainly prove to be better for cognitive enhancement in small doses than others.”
Although some users experience also unwanted effects, psychedelic microdosing is more often claimed to bring relief for such conditions such as depression and ADHD (Fadiman & Korb 2019; Lea et al. 2020), which were already mentioned by Albert Hofmann for what ‘very small doses of LSD’ could be useful for, decades ago. The vast list of effects psychedelic microdosing is claimed to produce, now confirmed by an increasing amount of user and preclinical studies (Polito & Stevenson 2019; Hutten et al. 2019; Rifkin, Maraver & Colzato 2020) with some clinical ones completed (Yanakieva et al. 2019; Ramaekers et al. 2020) and others underway (MindMed Press Release 2020; see also Hupli et al 2019a; Wired 2019) require further attention in this field (Hupli 2019).
Fadiman together with Sophia Korb will present some unexpected results from their crowd-sourced research at ICPR2020.
Written by Aleksi Hupli as part of his upcoming PhD Dissertation in Sociology at the University of Tampere titled Smarter with Drugs. Cognitive enhancement drugs from users’ perspectives.
References:
Fadiman, J. (2011). The psychedelic explorer´s guide. Safe, therapeutic and sacred journeys. Park Street Press
Fadiman, J. & S. Korb (2019). Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. Journal of Psychoactive Drugs, 51(2), 118-122.
Horowitz, M. (1976). Interview with Albert Hofmann. Available at: https://hightimes.com/culture/albert-hofmann-lsd-interview/
Hupli A., M. Berning, A. Zhuparris & J. Fadiman (2019a). Descriptive assemblage of psychedelic microdosing: netnographic study of Youtube™ videos and on-going research projects. Performance Enhancement & Health, 6,( 3–4), 129-138.
Hupli, A. (2019). ECR Spotlight: Psychedelic Microdosing – From Silicon Valley Hype towards Placebo-Controlled Science. In HED Matters, Vol 2, Issue 2. Available at: https://humanenhancementdrugs.com/wp-content/uploads/HED-Matters-Issue-3.pdf
Hutten, N., Mason, N., Dolder, P. & K. Kuypers (2019). Motives and Side-Effects of Microdosing With Psychedelics Among Users. International Journal of Neuropsychopharmacology, 22(7), 426–434.
Kuypers, K., Ng, L., Erritzoe, D., Knudsen, G.M., Nichols, C.D., Nichols, D.E., Pani, L. Soula, A. & D. Nutt (2019). Microdosing psychedelics: More questions than answers? An overview and suggestions for future research, Journal of Psychopharmacology, 33(9), 1039-1057.
Lea, T., Amada N. & H. Jungaberle (2020). Psychedelic Microdosing: A Subreddit Analysis. Journal of Psychoactive Drugs, 52, 101 – 112.
Lea, T., Amada, N., Jungaberle, H., Schecke, H., Scherbaum, N. & M. Klein M (2020). Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders. Psychopharmacology, 237,1521 -1532.
Mishra, S. (2018). Microdosing at Work: Reworking Bodies and Chemicals. Essay part of an online supplement to the Openings collection on “Chemo-Ethnography” edited by Nicholas Shapiro and Eben Kirksey in the November 2017 issue of Cultural Anthropology. Available at: https://culanth.org/fieldsights/1307-microdosing-at-work-reworking-bodies-and-chemicals
Nichols, D., Roseman, L. & C. Timmermann (2018). Psychedelics: from pharmacology to phenomenology. An interview with David Nichols. ALIUS Bulletin, 2, 75-85.
Passie, T., Halpern, J.H., Stichtenoth, D.O., Emrich, H.M. & A. Hintzen (2008). The pharmacology of lysergic acid diethylamide: A review. CNS Neuroscience & Therapeutics, 14, 295–314.
Passie, T. (2019). The Science of Microdosing Psychedelics. Psychedelic Press.
Polito, V. & R.J. Stevenson (2019). A systematic study of microdosing psychedelics. PLoS ONE, 14(2): e0211023
Ramaekers JG, Hutten N, Mason NL, et al. A low dose of lysergic acid diethylamide decreases pain perception in healthy volunteers. Journal of Psychopharmacology. August 2020. doi:10.1177/0269881120940937
Rifkin, B. D., Maraver, M. J. & L. S. Colzato (2020). Microdosing psychedelics as cognitive and emotional enhancers. Psychology of Consciousness: Theory, Research, and Practice. Advance online publication. https://doi.org/10.1037/cns0000213
Sessa, B. (2017). Psychedelic renaissance. Reassessing the role of psychedelic drugs in 21st century psychiatry and society. 2nd edition. Muswell Hill Press.
Yanakieva, S., Polychroni, N., Family, N., Williams L.T.J., Luke D.P. & D.B. Terhune (2018). The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial. Psychopharmacology,  236(4), 1159-1170.

The biggest challenges for psychedelic science today

Over the last decade, psychedelics have made a comeback in the world of research and academia. As they enter into a new phase of clinical trials, they bear the promise of improving people’s well-being by reducing their depression and anxiety, helping them overcome addiction, or even helping them cope with death and bereavement. This has caused a wave of new publicity, acceptance, and enthusiasm around psychedelic science.
Given that this area of research has been taboo for many decades, there is reason to be optimistic. There is an amount of new data coming in from numerous new clinical trials across various patient groups. As we anticipate the results of these investigations, it is equally important to remain critical, however, in order to ensure that this newly found enthusiasm does not reinstate the myth of the magic bullet that will ultimately cure all our mental ailments.
As research is being conducted in ever more places, some key challenges for the field are also becoming apparent. This piece wants to address those scientific issues as psychedelic science moves forward.
Science in Crisis
The scientific study of psychedelics is not immune from broader crises that are currently ongoing in the scientific realm, like the replication crisis, the lack of Open Science practices and the increasingly privatized funding of research.
The replication crisis comes from research that has shown that many results across different scientific studies cannot be reproduced. This has sometimes led to questionable research practices, such as modifying the results, fabricating data, or selective reporting of false positive findings, by individual actors. Prior hypotheses most often do not yield positive results, and researchers are often faced with unexpected findings.
Publishing these chance findings becomes problematic if the researchers do not clearly demarcate them as such, and conceal the failure of the initial hypothesis and post-hoc explanation of their findings. According to a meta-analysis conducted by Daniela Fanelli (2009), up to 72% of all scientists admit to witnessing questionable research practices concerning the behavior of their colleagues. Misconduct was reported most frequently in the areas of medical and pharmacological research, hence the area of psychedelic research is likely to be implicated. This is something to be acutely aware of.
Positivity bias
Many researchers in the field are understandably psychedelic enthusiasts. This bears a significant risk of selective reporting and motivated reasoning. The promise of psychedelics shown in clinical trials has already led to a nearly one-sided emphasis on the positive effects in the scientific literature, while ignoring the potentially adverse consequences such as mystic ego inflation, neuroticism, or the potential to induce false memories.
Combined with the earlier mentioned broader current problems in science, these over-positive tendencies are incentivized on a community-wide level due to a strong bias towards publishing positive findings, while the negative results are left unpublished in a file drawer.
This problem may be especially pertinent given the relatively high costs and investments involved in conducting psychedelic research, thereby creating a strong incentive for publishing positive results. And what may further limit the researcher’s degree of freedom, is that most studies on psychedelics are sponsored by private foundations with a vested interest.

Open Science practices
Many of these issues can be addressed by adhering to the guidelines of the Open Science Framework. This includes the preregistration of all hypotheses, the study design, data collection methods, and analysis pipelines to increase transparency throughout every step of the scientific process.
Many journals even offer the opportunity of depositing a research question and study design with a registration service or journal before conducting a scientific investigation. Future studies in the domain of psychedelic research would do well by making use of these practices in order to increase the credibility of their findings, and devote extra energy towards replicating some of the existing results via independent research groups.
Placebo-problem
The altered states resulting from psychedelics differ so profoundly from other substances, that there is an ongoing search for a good placebo. In a study of mystical experiences, methylphenidate hydrochloride (Ritalin) was used as a placebo (Griffiths, Richards, Mccann, & Jesse, 2006), in studies of psilocybin to treat anxiety in advanced stage cancer patients, niacin (vitamin B3, which produces flushing) was used as a placebo. And in a study of ayahuasca as treatment for depression researchers used zinc sulfate as a placebo, which may induce nausea and vomiting, playing into one of the commonly expected side effects of the hallucinogenic brew. (de Fontes, 2017).
Even within the classical pharmacological research framework for antidepressants, participants could often guess their test condition – which is known as ‘breaking blind’. This boosts the risk of reporting positively on their perceived mental state due to social desirability.
Psychedelic research is particularly prone to these dangers given the profound changes of subjective experiences, which cannot be easily mimicked with active placebos. This inherent risk will always beg the critical question if the subjective effects of psychedelics are determined by social desirability, prior expectations, or suggestibility of the participants.
Current research has partially addressed the placebo-problem by using different dose ranges. For instance, a microdose, minidose, and full-dose within the same cohort. However, the contrasting method of cognitive science and neuroimaging techniques itself, may be a source of ambiguity when interpreting modern day findings.
Comparing Altered States
On a fundamental level there is still a critical gap between an empiric understanding around altered states of consciousness, their underlying mechanisms and their application within clinical practice. We don’t know yet how the effects of psychedelics compare to other methods that have been used to induce altered states of consciousness, such as meditation, sensory deprivation, or breathing exercises. And we’re not good at measuring them.
The renowned theory of decreased Default Mode Network connectivity in response to psychedelics, may also have been driven by the effects of the placebo condition. Extreme boredom and mind wandering are associated with heightened activity of the Default Mode Network, which may create an exaggerated impression that psychedelics decrease the activity whereas in fact the placebo condition is increasing it.
Only relying on these types of contrasts may create a one-sided impression that Default Mode Network activity and ego-dissolution are primary mechanisms of action in psychedelics, while disregarding subjective accounts of indigenous ayahuasca practices wherein the ego remains intact.
Future research should address these nuances and develop more elaborate or diverse blinding methods, while an even more effective line of research could focus on comparing psychedelics to altered states across the full diversity of conscious experience.
This way, researchers may draw more elaborate conclusions by comparing the commonalities and differences between the neurophenomenology of different induction methods.
Systematic Bias
Like any other field, psychedelic research is not exempt from systematic biases that stem from cultural or socioeconomic differences amongst their respective participants. In the field of psychology, this problem is also known as the W.E.I.R.D bias: the majority of all participants are recruited from Western, Educated, Industrialized, Rich, and Democratic societies.
Given that tribal cultures compared to people from WEIRD populations exhibit significant differences in the most paradigmatic examples of psychology (such as the Müller-Lyer illusion), the subjective experience of psychedelics may be equally contingent on cultural differences.
In the area of clinical research, it is likewise important to represent a diverse sample of society that includes members of marginalized cultures or economic status, or risk inheriting biases that are systemic to society.
And while the contextual effects of set and setting are widely acknowledged within the psychedelic research community, future studies should aim to validate their underlying mechanisms in a cross-cultural manner.
The way forward
Much of the research on psychedelics has focused on extreme cases to make psychedelics more politically acceptable for research, like getting psilocybin approved for a study of terminally ill patients, and treating patients who are suffering from treatment-resistant depression. This has created large-scale clinical samples of patients where the etiology of their mental disorders is not represented in a fine-grained manner.
While it is important to test the efficacy of psychedelics on a large scale, it is equally important to maintain a fine-grained perspective as we investigate these substances in a stratified manner. These incremental advancements may require patience and a healthy dose of criticism.
In the long run, it may not only advance the research of psychedelics but elevate the quality of research beyond the caveats and systematic biases of their scientific domain.

Do psychedelics make you more creative?


Creativity and psychedelics have been closely allied ever since recorded history began. We can find ancient mushroom art that was likely inspired by the psychedelic experience, and in more recent history, we have reports of inspiration from psychedelics abound from the Beatles to Steve Jobs to microdosing tech enthusiasts. 
James Fadiman (one of the speakers at ICPR) studied creativity with engineers and architects in the 1960s. Although the studies [1] weren’t up to today’s standards of double-blind, placebo-controlled, they did provide a first hint of what was to come.
The participants noted that they found solutions to problems they had been working on for months. In the studies they were given a moderately high dose of LSD or mescaline (100ug and 200mg respectively). Their inhibitions were reduced, ideation flowed more easily, and they could see the problem from different perspectives.
“Looking at the same problem with (psychedelic) materials, I was able to consider it in a much more basic way, because I could form and keep in mind a much broader picture.” – study participant
Creativity itself is a tricky concept to define and measure. It can be defined as the ability to produce original and unusual ideas, or to make something new or imaginative. You can see creativity as a process that happens by combining information in new ways. This process is most commonly divided into two parts: divergent (generating ideas) and convergent (evaluating ideas) creativity.
Ben Sessa asked in 2008 if it was time to revisit psychedelics and creativity [2], as the creative process and the psychedelic experience shared many characteristics. But that since the 1960s, not many studies had looked into psychedelics and creativity.

Findings

Since 2008 there have been many studies on both the perceived effects (at macro- and microdoses) of psychedelics on creativity. A preliminary conclusion could be that psychedelics help with divergent creativity during the psychedelic experience, and possibly with convergent creativity during the integration afterward. A small selection of them found the following:
During a psychedelic experience with Ayahuasca, divergent creativity was slightly enhanced on one measure [3]. Participants in the study were more creative in identifying novel connections between pictures (PCT test).  Measuring one [4] and two [5] days after a psychedelic retreat with respectively a macrodose of psilocybin and ayahuasca, divergent creativity was also found to be enhanced.
In the study of the psilocybin retreat [4] however, the convergent creativity was impaired during the psychedelic experience. In the test they were worse at identifying a set connection between pictures. But convergent creativity was higher when they measured it seven days later. So although this measure of creativity was worse during a macrodose, it seemed to have improved a week later.
At the microdosing level, many people report being more creative. A survey study that included a test of creativity, on which Rotem Petranker worked, confirmed this [6]. The study found a weak correlation (r = 0.15) between microdosing and creativity.
How psychedelics lead to creativity is still being studied and Ido Hartogsohn points towards the meaning-enhancing properties of them as a possible mechanism [7]. If you’re not as critical of yourself, he states, then you might have more divergent ideas which can then be valuable after evaluation (convergent).
“By magnifying the perceived significance of creative challenges and insights, psychedelics provide users with the impetus to pursue new, less obvious lines of ideation that they might otherwise have ignored; and with enhanced motivation to explore new creative directions to their fullest ramifications.” (p. 129)

Chemistry 

How this happens at the level of brain chemistry is currently being investigated by researchers like Leor Roseman. One study [8] he worked on showed more general coherence and lower frontoparietal network activity whilst on a macrodose of psilocybin.
 


 
The coming decades will shed more light on what aspects of creativity psychedelics can influence. Retreats that work together with researchers, like the one Daan Keiman runs, may help provide insights.
The speakers above are among the 60+ speakers at the Interdisciplinary Conference on Psychedelics Research – taking place from the 24th to the 27th of September. Here, top researchers will showcase the latest multi-disciplinary insights from psychedelic science. More information at icpr2020.net.
 
[1] Harman, W. W., McKim, R. H., Mogar, R. E., Fadiman, J., & Stolaroff, M. J. (1966). Psychedelic agents in creative problem-solving: A pilot study. Psychological reports, 19(1), 211-227.
[2] Sessa, B. (2008). Is it time to revisit the role of psychedelic drugs in enhancing human creativity?. Journal of Psychopharmacology, 22(8), 821-827.
[3] Kuypers, K. P. C., Riba, J., De La Fuente Revenga, M., Barker, S., Theunissen, E. L., & Ramaekers, J. G. (2016). Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking. Psychopharmacology, 233(18), 3395-3403.
[4] Mason, N. L., Mischler, E., Uthaug, M. V., & Kuypers, K. P. (2019). Sub-acute effects of psilocybin on empathy, creative thinking, and subjective well-being. Journal of psychoactive drugs, 51(2), 123-134.
[5] Frecska, E., Móré, C. E., Vargha, A., & Luna, L. E. (2012). Enhancement of creative expression and entoptic phenomena as after-effects of repeated ayahuasca ceremonies. Journal of psychoactive drugs, 44(3), 191-199.
[6] Anderson, T., Petranker, R., Rosenbaum, D., Weissman, C. R., Dinh-Williams, L. A., Hui, K., Hapke, E., Farb, N. A. (2019). Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. Psychopharmacology, 236(2), 731-740.
[7] Hartogsohn, I. (2018). The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality, and creativity. Frontiers in neuroscience, 12, 129.
[8] Girn, M., Mills, C., Roseman, L., Carhart-Harris, R. L., & Christoff, K. (2020). Updating the dynamic framework of thought: Creativity and psychedelics. NeuroImage, 116726.

Europe’s psychedelic science renaissance has started


The Old World has had its own remarkable history concerning psychedelic research – it was after all the continent where Albert Hofmann first discovered LSD and where Dutch professor Jan Bastiaans treated the trauma of Holocaust survivors with the same substance for many decades.
Now, the psychedelic wave has washed ashore again in Europe, and we’re here to witness it first-hand. In this piece, we have attempted to give the most complete overview of the current wave of psychedelic science that’s happening on the European continent.
The past decade has seen a new wave of academic research into psychedelics – a fledgling but true renaissance of this scientific frontier. Currently, phase 2 trials are underway for the study of MDMA-assisted psychotherapy in the treatment of PTSD in Europe, psilocybin studies are underway in more than one nation, and multiple academic hubs facilitate growth of the field.
Below we summarize the experimental psychedelic studies in the fields of (clinical) psychology, psychiatry and neuroscience in Europe. Many of these studies are still young, and will take years to complete. Still, this decade will likely harbor historic moments in moving psychedelics into the mainstream in Europe – because psychedelics science has only just started scratching the surface of what’s possible.

Research hubs

  • Imperial College in London
  • The University of Basel
  • University of Zurich – the latter being an official study site of the Heffter Research Institute.

In addition to the research carried out at these universities, two multi-site trials – sponsored by the non-profit organisation MAPS (mdma) and the for-profit Compass Pathways (psilocybin) – are underway in Europe, thereby involving various academic treatment centers in Europe in psychedelics research.
There are a few main research hubs in Europe where most of the psychedelics research is concentrated. At these locations, multiple studies below are performed.

Experimental research

Below we summarize the current European research into three psychedelic substances: LSD, psilocybin or mdma3.
Experimental research can be broken down into two basic categories. The first are the clinical trials, in which psychedelics are administered to patient populations. The other is neurobiological research, in which the effect of psychedelics on healthy participants are studied.
Of course, the field of psychedelic research is much broader and includes naturalistic, historical and qualitative research methods such as used in the social sciences and humanities. For lack of a central registry in which such studies are enlisted, it is harder to keep track of ongoing non-experimental (social scientific) research.
Clinical Studies 👩‍🏫First, let’s look at all the clinical studies that are going on.

LSD studies in Switzerland

“LSD is a Baseler product,” said Matthias Liechti to the Guardian about the most famous product from Basel, Switzerland. Liechti – a professor in clinical pharmacology at University Hospital Basel and speaker at ICPR 2020 – studies the effects of LSD on the human mind and body. “It’s tied to Basel’s history as a centre of pharmacology and innovation.”
How fitting that almost all research with LSD is taking place in the substance’s ‘place of birth’, Basel.

  • LSD as Treatment for Cluster HeadacheUniversity Hospital Basel
    Cluster headaches are the most painful and debilitating form of headache, for which available medication often does not work sufficiently. LSD has been reported to abort cluster headache attacks and to decrease their frequency. Headed by lead investigator Professor Matthias Liechti and conducted by Yasmin Schmid, MD, this double-blind, placebo-controlled crossover study will administer LSD (or a placebo) to 30 patients suffering from cluster headaches. They will receive three doses of 100 micrograms within a three week period.
  • LSD Therapy for Major DepressionUniversity Hospital Basel.
    This study will test the efficacy of LSD therapy in patients with Major Depressive Disorder and is recruiting 60 patients. The treatment group will undergo two sessions with LSD (100 & 200 μg) and the control group will undergo two sessions with an active placebo (25 μg and 50 μg LSD). This study is lead by Prof. Dr. med. Stefan Borgwardt and has just started recruiting. It is estimated to be completed by the summer of 2023.
  • LSD Treatment for Anxiety in Severe Somatic DiseasesUniversity Hospital  Basel 
    In this study, 40 patients with an Anxiety Disorder will be given a single dose of LSD. Due to its cross-over within-subjects design, all patients will receive both a placebo dose and an active dose: 200 μg LSD. This study is a collaboration between University Hospital Basel and the private practice of Peter Gasser, MD, who is also the study’s principal investigator.


Imperial College in London has recently founded the world’s first Centre for Psychedelics Research

Psilocybin studies in Europe

About a third of all experimental studies with psilocybin are happening in Europe. All of the European psychedelic research hubs – University of Zurich, University Hospital Basel and Imperial College London – are currently involved in clinical or neurobiological research with psilocybin. Europe also hosts 11 of the 21 sites of the clinical study on psilocybin therapy for treatment resistant depression – for which its sponsor Compass Pathways was granted a breakthrough therapy status by the FDA in 2018.
Clinical studies with patients:

  • Psilocybin vs Escitalopram for Major Depressive DisorderImperial College, London 
    This study is recruiting 50 patients suffering from depression in order to compare the efficacy and mechanisms of action of psilocybin with the SSRI Escitalopram. Principal investigator of this study is Professor David Nutt.
  • Clinical and Mechanistic Effects of Psilocybin in Alcohol Addicted Patients – University of Zurich
    This study will test the efficacy of psilocybin for treating alcohol use disorder and study its underlying neurobiological mechanisms in a randomized, placebo controlled, double blind study. 60 participants are recruited for this study. Six weeks after undergoing a withdrawal treatment, they will either receive a single dose of placebo or a single dose of psilocybin (25 mg, orally). Dr. Katrin Peller is the principal investigator in this study.
  • The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression. This is a multi-site clinical trial with 21 study locations in North America and Europe, sponsored by the (for profit) organization Compass Pathways. The following European sites are involved in this study:

Enhed for Psykiatrisk Forskning, Psykiatrien i Aalborg – Aalborg, Denmark
Tallaght University Hospital – Dublin, Ireland
Groningen University Medical Centre – Groningen, the Netherlands
Leiden University Medical Centre – Leiden, the Netherlands
Utrecht University Medical Centre – Utrecht, the Netherlands
Hospital de Dia Numancia – Barcelona, Spain
Institute Hospital del Mar of Medical Research (IMIM) – Barcelona, Spain
Clinical Research and Imaging Centre – Bristol, United Kingdom
Wolfson Research Centre, Campus for Ageing and Vitality – Newcastle Upon Tyne, United Kingdom
Kings College London, Institute of Psychiatry, Psychology and Neurology – London, United Kingdom
Greater Manchester Mental Health Foundation Trust – Manchester, United Kingdom

MDMA studies by MAPS
The Multidisciplinary Association for Psychedelics Studies from the United States -and headed by Rick Doblin- is planning phase 2 and phase 3 clinical trials to develop MDMA-assisted psychotherapy into an approved treatment for PTSD. In order to conduct part of these trials in Europe, MAPS has created a European-based subsidiary.
Six study sites in five European countries are involved in the “Open Label Multi-Site Study of Safety and Effects of MDMA-assisted Psychotherapy for Treatment of PTSD With Optional fMRI Sub-Study”:

  • Czechia – NUDZ – National Institute of Mental Health, Klecany
  • Norway – Sykehuset Østfold Hf, DPS Norder, Moss
  • Netherlands
    • Maastricht University, Dept of Neuropsychology and Psychopharmacology – Maastricht
    • Stichting Centrum ’45/Arq – Oestgeest
  • Portugal – Fundação de Anna de Sommer Champalimaud, Lisbon
  • United Kingdom – University Hospital of Wales – Research Facility, Cardiff

The University of Bristol and Imperial College London are collaborating in an ongoing study on mdma as a treatment for alcoholism. The “Bristol Imperial MDMA in Alcoholism Study (BIMA)” is an open label within-subject feasibility study in 20 patients with Alcohol Use Disorder who have recently undergone detoxification. The study is conducted by Ben Sessa, MD and its principal investigator is Professor David Nutt.

🧠 Studies into the psychedelic state itself

LSD AND PSILOCYBIN

  • Direct Comparison of Altered States of Consciousness Induced by LSD and PsilocybinUniversity Hospital Basel
    Both LSD and psilocybin are used as pharmacological tools in neuroscience. However, there are no modern studies comparing these two substances directly within the same clinical study and using validated psychometric tools. In this study the researchers will compare the acute effects of LSD, psilocybin and placebo. 30 Healthy participants will be administered various dosages of these psychedelics, the effects of which will be measured with various assessment tools.The study is conducted by Friederike Holze and Professor Matthias Liechti.

  • Comparative Acute Effects of LSD, Psilocybin and Mescaline  –University Hospital Basel
    This study compares the acute effects of LSD, psilocybin, mescaline and placebo in a double-blind, placebo-controlled, 4-period cross-over design. In four separate sessions, the 25 healthy participants will receive 100 μg LSD, 20 mg psilocybin, 300 mg mescaline and a placebo. Professor Matthias E. Liechti is the principal investigator in all three of the above psilocybin studies taking place in Basel.
  • Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the SelfUniversity of Zurich
    In terms of the number of participants in a single study, this is currently the largest experimental study with psilocybin in Europe. 140 Healthy participants are divided into 4 groups, each with it’s own double-blind, placebo-controlled setup. One of the groups consists of long-term and short-term meditators during a 5-day group retreat. The aim of the study is to identify neural signatures, behavioral and phenomenological expressions of self-related processes.
  • Characterization of Altered Waking States of Consciousness in Healthy Humans – University of Zurich
    This study uses a combination of transcranial magnetic stimulation (TMS) and high density electroencephalography (hd-EEG) to measure the level of consciousness in a pharmacologically altered waking state of consciousness (induced by psilocybin).Lead investigator Professor Franz X. Vollenweider and his team are recruiting 25 healthy participants for this study.

MDMA and fear

  • University Hospital Basel is currently recruiting healthy participants for a study called “The Effect of MDMA (Serotonin Release) on Fear Extinction”. Fear extinction is a psychological process that plays a crucial role in treating disorders such as PTSD. Although MDMA has been shown to enhance the extinction of fear in animals, no data exists on the effect of MDMA on fear extinction in humans. The lead investigator in this study is Professor Matthias E. Liechti, MD.

Should you be interested in contributing to science by participating in a clinical/neuroimaging study: most of these studies are still recruiting. Look them up on this website to study their inclusion and exclusion criteria and to find out more.
This overview only covers the research that has been registered at clinicaltrials.gov and is therefore not exhaustive. Do you know of other ongoing experimental studies in Europe, feel free to reach out to us!

1 The FDA (Food and Drug Administration in the US) granted the label ‘breakthrough therapy’ to mdma-assisted psychotherapy for PTSD (sponsored by MAPS) in 2017. In 2018 the treatment of depression with psilocybin (sponsored by Compass Pathways) was granted the breakthrough therapy status, followed by a designation for the research by Usona in 2019, also for the treatment of major depression with psilocybin assisted therapy.
2 Of course there are other psychedelics, but for the scope of this article we focus on the most popular substances for clinical research. We also focus on trials that induce psychedelic effects – unlike for example many ketamine trials where sub-psychedelic dosages are used.

Alicia Danforth on ethical challenges in psychedelic medicine

Alicia Danforth, PhD, is a licensed clinical psychologist and researcher and has participated in three major studies on psychedelic-assisted therapy, the latest of which is still unpublished. She began her work in clinical research with psychedelic medicines as a coordinator and co-facilitator on the pilot study of psilocybin treatment for existential anxiety related to advanced cancer. More recently, she was an investigator for the first study of MDMA-assisted therapy for the treatment of social anxiety in autistic adults.
Your first study with psychedelics was about end-of-life anxiety, the second one was about social anxiety, and this latest one also has to do with anxiety to some extent. Is there a thread regarding anxiety in your research work?
I didn’t set out to go that way. The first study had to do with anxiety facing the end of life, yes. But to be candid, social anxiety wasn’t the initial focus of the autism research. I had made the false assumption that autistic individuals lack empathy, which isn’t more than an outdated cliché that I mistakenly took at face value. My initial thinking was that MDMA is an empathogen, so it might help this population experience empathy.
Once I started interviewing autistic adults for my dissertation, I found out that they were quite empathic in many domains of empathy, and they told me what they were struggling with is social anxiety. The desire to connect was there, but the ability to read social cues and to know how to integrate into a group conversation or initiate a friendship is what they needed help with. That’s how working with social anxiety as an indication came about.
So with hindsight, yes, you could say that anxiety is a thread that has run through most of the clinical work that I’ve been involved with. Anxiety disorders are the most common mental health diagnoses in the United States, and they have been a good match so far with psychedelics-assisted therapy.
Your latest research with psychedelics is about psychological distress in long-term AIDS/HIV survivors. Can you tell us more about this new study?
I want to clarify that I’m not one of the investigators on this study, I’m a lead clinician. I co-facilitated the therapy groups and the psilocybin treatment sessions. Dr. Brian Anderson initiated this study at UCSF. San Francisco has been a hub of HIV medicine, and Brian became aware that there’s an underserved population of long-term survivors who acquired the HIV virus back in the 1980’s or early 1990’s. As a result of losing so many of their friends and because of the impact of HIV on their lives and on the community, they were living with a high degree of demoralization.
Dr. Anderson wanted to explore if treatment with psilocybin-assisted therapy could help improve overall quality of life and reduce anxiety and depression symptoms. The first phase has been completed, the data are analyzed, and a manuscript has been prepared. All I can say right now is that the outcomes were encouraging.
One way in which this study was very innovative is that we worked with a group therapy model, where the participants prepared as a group, and then each one had an individual psilocybin-assisted therapy session, and they came back together to do their integration work as a group. We’re frequently asked if everyone took the psilocybin all together, and they did not. I don’t think we’re quite there yet, but I couldn’t help but wonder what that might be like someday.
At the upcoming ICPR 2020 conference in April, you’ll speak about ethical challenges within psychedelic medicine. Can you explain its importance?
It’s no secret that psychedelics present unique challenges when it comes to ethical considerations and boundaries. These substances place people in profound altered states of consciousness, and with that shift can come increased suggestibility and vulnerability. We’re working with such novel treatment paradigms that we need novel approaches to how the individuals who are entrusted with the roles of therapist or guide should be vetted, trained, and supervised.
Could you elaborate?
Well, it became very apparent to me that there are certain personality types that are drawn to situations in which they’re in close proximity to people who are vulnerable and open. They seek to manipulate and have a very unhealthy relationship with power. Back in the 60’s and early 70’s, when people were working with these substances in controlled and uncontrolled settings, there were problems with individuals who would transgress boundaries. And today, we’re plunging headlong into a new era where billions of dollars are accruing to throw money at this enterprise; there’s such a rush to do it quickly.
But, we don’t have the structures in place to keep the participants in research settings -and eventually customers in commercial settings- safe from abuses of power. So, I’ve started proposing that we need to look at other medical professions where they have to accommodate similar levels of vulnerability, such as anesthesiologists, pediatricians and gerontologists. We need to agree on which methods we’re going to have to employ to train and supervise peers. We don’t have a good system for winnowing out individuals who seek to do this work who have clinically significant narcissistic traits or psychopathy. How are we going to gatekeep? If we don’t talk about this responsibility and address it, we’re at risk of running into trouble again.
Alicia Danforth’s talk at ICPR 2020 will be entitled: “Getting Our House in Order: Advancing the Ethics of Psychedelic Medicine and Psychotherapy from Storming to Norming

A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
Link to full text

Lecture: Michael Pollan on psychedelics

On Monday December 10th, OPEN is hosting an event with best-selling author Michael Pollan. On this evening, he will discuss his own research into psychedelics, and the implications of the latest scientific findings for therapy, consciousness and personal transformation.
In his newest book ‘How to change your mind‘, best-selling author and journalist Michael Pollan investigates the science of psychedelics, and their relation to consciousness, therapy and transformation. Pollan is best known for his award-winning writing on food, such as ‘The Omnivore’s Dilemma’ and ‘Food Rules’. His style of ‘immersive journalism’ is ideally suited to explore the world of psychedelics, and he reluctantly experiments with LSD, psilocybin mushrooms and 5-MeO-DMT to find out what psychedelics are all about. In addition he interviews many neuroscientists and therapists.
The result is a fascinating journey through the history of psychedelics, moving from promising psychedelic treatment for alcoholism and death anxiety in the fifties to present-day neuroscience research, and the renewed interest in therapy for depression, addiction and trauma. Can psychedelics help us to improve our relationship towards ourselves and our surroundings? Come and find out on December 10th.
Doors open at 19:30, and the program starts at 20:00. Address: Tivoli/Vredenburg, Vredenburgkade 11, Utrecht.
Tickets are in limited supply and can be bought here.
After the lecture, you will be able to purchase the recent Dutch translation of ‘How to change your mind’. Michael Pollan will be available to sign your books.