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PSYCHEDELICS AND Self-Administration: pros and cons with Dr. Michiel van Elk

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

Author: Jasper Lucas

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Jasper: Really interesting, I never knew.

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

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

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

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

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

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

What are the effects of psychedelics on neuroplasticity?

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

Author: Maxim Siegel
Interviewee: Cato de Vos

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

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

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

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

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

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

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Q&A with Cato de Vos, MSc.

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

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

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

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

Question 2. How can neuroplasticity be measured?

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

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

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

Question 3. By which mechanisms do psychedelics induce neuroplasticity?

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

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

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

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

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

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

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

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

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

Question 6. Any additional thoughts on neuroplasticity and psychedelics ?

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

References:

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

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

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

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

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

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

Illustration modified version of Milad Fakurian on Unsplash

How AI and language can help predict psychedelic treatment outcomes

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

Author: Maxim Siegel
Illustration: Anna Temczuk

Language as a diagnostic tool

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

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

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

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

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

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

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

Accurate Predictions

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

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

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

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

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

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

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

References:

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

2. Fraser, K. C., Meltzer, J. A., & Rudzicz, F. (2016). Linguistic Features Identify Alzheimer’s Disease in Narrative Speech. Journal of Alzheimer’s disease : JAD, 49(2), 407–422. https://doi.org/10.3233/JAD-150520

3. Carrillo, F., Sigman, M., Fernández Slezak, D., Ashton, P., Fitzgerald, L., Stroud, J., Nutt, D. J., & Carhart-Harris, R. L. (2018). Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. Journal of affective disorders, 230, 84–86. https://doi.org/10.1016/j.jad.2018.01.006

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

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

6. Cox, D. J., Garcia-Romeu, A., & Johnson, M. W. (2021). Predicting changes in substance use following psychedelic experiences: natural language processing of psychedelic session narratives. The American journal of drug and alcohol abuse, 47(4), 444–454. https://doi.org/10.1080/00952990.2021.1910830

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

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

Author: Stephan Tap

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

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

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

The Netherlands at the forefront of psychedelic research

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

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

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

New Research

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

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

Barriers to breakthrough therapy status

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

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

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

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

Central management and the Netherlands

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

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

References:

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

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

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

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

’Psychedelic professors’ on the rise as universities expand courses on psychedelics

If you attended university or college and didn’t have an option to take a course on psychedelics – that was because they were practically nonexistent until very recently. Up to the beginning of this century, getting educated about psychedelics meant researching on your own, learning from elders, attending the few conferences that existed, reading available journal articles and books, or maybe joining secret psychedelic societies (in person or on the internet).

But today we are simultaneously experiencing a rise in international psychedelic research and an international acceptance of this field as a genuine, revived field of science. As a result, there is an emergence of university courses. And not just in a few places, but in some very prominent universities.

The psychedelic professors

The relative novelty of this educational endeavor spiked our interest: What are the types of courses offered? How are they organized and taught? What type of students are taking them? And what are the biggest challenges in teaching about psychedelics? We’ve interviewed three professors of current psychedelic courses at prominent research universities, who can rightfully call themselves psychedelic professors: Kim Kuypers (Maastricht, NL), Gianni Glick (Stanford University CA, USA), and Brian Pace (Ohio State University, OH) 

Kim Kuypers, PhD, is an Associate Professor of Psychology and Neuroscience at Maastricht University in the Netherlands. Dr. Kuypers focuses on “Me We Biology”, trying to understand the biology of mental well-being. She researches psychedelics and their effects on cognition, creativity, hormones, and the mechanisms underlying these effects. Dr. Kuypers will be a speaker at this year’s ICPR conference

Giancarlo “Gianni” Glick, MD, is a 3rd-year psychiatry resident at Stanford whose psychiatric focus is on the interdependence of emotional and physical well-being for his patients. He is also the organizer of the Stanford Psychedelic Science Group.  

Brian Pace, PhD, is an affiliate scholar with the Centre for Psychedelic Drug Research and Education in the College of Social Work and a lecturer in the Department of Plant Pathology at The Ohio State University. Trained as an evolutionary ecologist, Brian studied agroecology, climate change, and ethnobotany. He is the Politics and Ecology Editor at the 501c3 psychedelic watchdog Psymposia and is currently a part of the team organizing Psychedemia, an interdisciplinary psychedelics conference scheduled for August of 2022 at Ohio State.

Here is what they teach, how they teach it, and why it is important they do it. 

Q: Which courses on psychedelics do you teach?

A: Kuypers (Maastricht) “Psychedelic Medicine” is an 8-week long elective course for third-year bachelor’s students which is housed in Maastricht’s department of psychology. I also teach a first-year elective course in the same department, called “Drugs in the Brain”. This is for first-year students and is only 4 weeks long. This helps to serve as good preparation for those who will take the psychedelics class. 

A: Glick (Stanford) “Introduction to Psychedelic Medicine” is a 10-week course, housed in the department of psychiatry at Stanford Medical School. This semester we have 187 students enrolled. It is an elective course and the make-up is about 70% undergraduates and the rest are graduates of all kinds. We also have many auditors ranging from neuroscience postdocs to attending psychiatrists. This makes for a huge range of expertise and familiarity with psychiatry. 

A: Pace (Ohio State) “Psychedelic Studies: Neurobiology, Plants, Fungi, and Society” is a 14-week/one-semester course and it is through the Department of Plant Pathology. The course is for undergraduate bachelor’s students, without any prerequisites, but I frequently have graduate students as well. The majority are third and fourth-year students. There is also a new course being taught in our department called “Psychedelic Bioethics,” taught by my colleague, Dr. Neşe Devenot.  

Kim Kuypers teaches “Psychedelic Medicine” at Maastricht University to third-year bachelor’s students. She is also a speaker at ICPR 2022.

Q: What are the key learning outcomes for your students?

A: Kuypers (Maastricht) I want the students to know about the rich history of psychedelics and to be educated on both the positive and negative aspects of these substances. I place a major focus on how to properly read a scientific article: reviewing the research methodology, analyzing the results, and having a critical mind about it.  I see this course as really the first way of getting the students acquainted with psychedelics and from here they should be able to navigate the future research that comes out with a better eye, and maybe also be inclined to get into the research and/or work in psychedelic-assisted therapies themselves. 

A: Glick (Stanford) This question keeps me up at night, but I hope for a good cause – there are so many decisions about what to present, how to engage, what sequence of information makes the most sense. Ultimately, I want to prepare students to critically interact with everything they hear in the media and in the scientific literature about psychedelics. This course covers the foundational principles, history, and context for these students to then ask more questions and hopefully contribute to the field of psychedelics, themselves. I think one of the first questions we try to ask is: What does it even mean to call psychedelics medicines? And in doing so understand that we are applying a particular frame to it, specific to this pre-FDA-approval moment in time and space. While it’s nicer pedagogically to stay focused on psychedelics as a medicine, we also tell them that psychedelics can be many other things: sacraments, recreation, and so on. But for this course, we focus on them as medicines.

A: Pace (Ohio State) As the instructor of a course on psychedelics it is my job to prepare students to engage intellectually, become better communicators, and to have better conversations around a controversial topic that is rapidly taking center stage. Frankly, there are a lot of grifters in the psychedelic space, people who are attempting to own the space, and so part of my responsibility is to provide students with tools to critically evaluate psychedelic science and health claims, the job market they may enter, and to hopefully have these students make informed choices.

Q: What is the greatest challenge in teaching your course on psychedelics? 

A: Kuypers (Maastricht) I haven’t had too many difficulties in teaching this material. I did have an incident where I was teaching about animal research that was done with MDMA to investigate neuronal death, and in doing these studies I discussed the methodology which included decapitation to further look at their brains. As a result of saying so I had a student who left the room because they could not bear to hear this type of work. Though not directly related to in-class learning itself, I have had emails sent to me from parents of children who have abused drugs who question whether I am being too positive about these compounds, even going so far as calling me the devil. But in the 4 years of teaching this course, I have not faced many challenges from students. 

A: Glick (Stanford) Trying to figure out – what are the first principles of psychedelic medicine?  Where do you start?  How to strike a balance between asking big, zoomed-out, philosophical questions of human life and suffering (which I think is what this is really about), while staying in close contact with the data, the practice of medicine, counterpoints to my own views, and a sober take on all of this. How to teach students a kind of big picture schema that new ideas and facts and questions can fit into.

A: Pace (Ohio State) Psychedelics are inherently interdisciplinary. I’m not a psychiatrist. I’m not a social theorist. I’m not a political scientist. Yet these topics are as necessary to address as botanical, mycological, or neurochemical considerations–even though more broadly they may exceed the scope of my expertise. This can be challenging at times, but manageable. What is truly challenging is that issues like colonialism, addiction, and traumatic experiences are discussed in my course, and the reality is that some of the mental health distress faced globally is experienced personally by some of my students. Real injustice never gets easier to talk about, especially with those who are directly impacted by it.

One early psychedelic professor is Dr. Neşe Devenot – now an Affiliate Scholar at the Center for Psychedelic Drug Research and Education at Ohio State University.
She advocated for Psychedelic Studies courses for years, formally so in an essay in 2011 entitled “A Declaration of Psychedelic Studies”. Her first class, “Poetic Vision and the Psychedelic Experience,” ran from 2011 to 2012. A later class called Drug Wars had a focus on psychedelics and featured guest lectures from Matt Johnson and others working in the field. Her “Higher Dimensions in Literature” class in 2014 read McKenna and Castaneda. She went on to teach Psychedelic Studies at the University of Puget Sound from 2015 – 2018.

Q: What pedagogical tools do you use in your course? 

A: Kuypers (Maastricht) For both the “Psychedelic Medicine” 8-week course and the 4-week “Drugs of the Mind” course I use Problem Based Learning (PBL). This pedagogy works by bringing real-world problems to the class which functions as vehicles for students to have to look up things they don’t know, synthesize an answer based on their research and these problems are generally guided, often providing one part of a problem at a time.  An example of the last PBL assignment was a problem evaluating the positive and negative of the field of psychedelic medicine. In terms of course materials, I developed a course manual and we also use recent research articles for the “Psychedelic Medicine” course. In the 1st year course “Drugs of the Mind” course we use David Nutt’s “Drugs Without the Hot Air”.  I do most of the lectures but some of my colleagues help as well. We have a limited amount of time in these courses so we provide additional resources online for students to read and watch on their own. 

A: Glick (Stanford) Two years ago the course started as a lecture series, with a different speaker each week presenting on their area of expertise.  We updated the second iteration (last year) to have a more coherent through-line and progression of topics, with added small group discussion. And this year we tried to improve that further, so we spent the first third laying the foundational principles, the second third hearing from serious experts in the field (Brian Anderson, Jennifer Mitchell, Robin Carhart-Harris), and the final third weaving everything together.  The best session is always the last one when students give 5-minute presentations to the class on any topics or psychedelics subgenres they found interesting.  This year they taught us about psychedelics in China, the Eleusinian mysteries, research in psychotic disorders, and a bunch more.

A: Pace (Ohio State) This is a lecture-based course accompanied by reading articles and watching videos that conclude with 30-minute discussions each class. Since it is a course goal is to get students to have better, evidence-based conversations around psychedelics, students write weekly reading reflections showing that they are considering the material and reflecting on how they feel, and how these topics may connect to their life. Students also do presentations which are evaluated in part by peer review. From day one I am walking students through difficult, yet respectful conversations; you can’t understand psychedelics without touching on topics like consciousness, perception, religious experiences, and criminalization. 

Q: What do you believe is the ROLE of university courses in the psychedelic renaissance? 

A: Kuypers (Maastricht) It is incredibly important to have these available. I get requests from therapists and psychiatrists who did not get these types of courses in the curriculum of their educational training. Some of them also tell me of the cost for psychedelic-assisted therapy training from private institutions that can cost upwards of 20,000-25,000 Euros, which is crazy. Instead, this type of education should be embedded within all levels of university education from bachelor’s, graduate, and medical education. We definitely need psychedelic-assisted training for therapists in the universities (instead of the private organizations). 

A: Glick (Stanford) Similarly to how Johns Hopkins, NYU, and UCLA have stewarded the research through this kind of rigorous academic environment, there is this similar way that universities may offer a credible education, with a kind of peer review process, with a set of checks and balances where you can’t just teach anything. Secondly, doctors should know about this. For medical students and psychiatry residents to be competent about medicines their patients are in some cases already using and that may soon become legal, this should be part of the curriculum.

A: Pace (Ohio State) Psychedelics were abandoned by institutions following the Controlled Substances act in 1970. The new-agey, cultish stuff we see around psychedelics now, with tuning your chakras and merging souls or whatever: that is our fault. That’s an abdication of the responsibility to investigate interesting questions and to chase down data: to find out how things work.  So where we are now is a very timid and late re-entry to the subject, more so for education than research.  Psychedelic research didn’t end when the universities and governments abandoned it. It continued in the underground. The role of the university courses on psychedelics is to identify and evaluate high-quality information on the topic. We have a lot of catching up to do and I think that should be done with humility.

Addendum: The author of this article, Dr. Joey Lichter, is a volunteer for OPEN and ICPR, but also a chemistry professor who teaches a course titled “The Psychedelic Renaissance” at Florida International University in Miami, FL USA, thereby also qualifying as another psychedelic professor.

The Psychedelic Experience: A Manual Based on The Tibetan Book of the Dead

The Psychedelic Experience: A Manual Based on The Tibetan Book of the Dead. Timothy Leary, Ralph Metzner, and Richard Alpert. Penguin Books. ISBN: 978-0141189635

The authors process the concepts of death and rebirth presented in Tibetan Book of the Dead as a metaphor for the experience of ego death or depersonalization that is commonly experienced under the influence of psychedelic drugs. The book also describes broadening spiritual consciousness through a combination of Tibetan meditation techniques and psychotropic substances.

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LSD Psychotherapy: The Healing Potential of Psychedelic Medicine

LSD Psychotherapy: The Healing Potential of Psychedelic Medicine. Stanislav Grof. Multidisciplinary Association for Psychedelic Studies (MAPS). ISBN: 978-0979862205

Drawing on his 1960’s studies of LSD-assisted psychotherapy, Grof outlines a new cartography of the human mind, one which accounts for experiences such as shamanic trance, near-death experiences and altered states of consciousness. This vision is also the foundation for Dr. Grof’s revolutionary new Holotropic Breathwork.

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LSD, my problem child

LSD, My Problem Child. Albert Hofmann. Oxford University Press. ISBN: 978-0198840206

In a highly candid and personal account, the father of LSD details the history of his “problem child” and his long and fruitful career as a research chemist. An essential read for anyone wanting to learn about how LSD originated and Hofmann’s view on its transition to recreational use.

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The Teachings of Don Juan: A Yaqui Way of Knowledge

The Teachings of Don Juan: A Yaqui Way of Knowledge. Carlos Castaneda. Simon & Schuster. ISBN: 978-0671600419

A mixture of narrative experiences and scholarly analysis, this book describes the effects of three hallucinogenic drugs taken by a graduate student under the supervision of a Yaqui Indian shaman.

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

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

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

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