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On March 19 and 20, 2023, the European College of Neuropsychopharmacology (ECNP) organised the New Frontiers Meeting on Psychedelics in Nice, France. Various researchers and clinicians joined this event to talk about the current state of psychedelic-assisted psychotherapy (PAT). Here are some of the most interesting developments in the field of psychedelic research.

The ECNP New Frontiers Meeting: Psychedelics 2023 was kicked off by Gitte Moos Knudsen, the current Chair and president of the ENCP and professor of the neurology department at the Rigshospitalet and University of Copenhagen, Denmark. She laid out the program of the conference that consisted of three sub-topics, including pharmacology, clinical aspects, and clinical trials. Furthermore, Knudsen presented the Gartner Hype Cycle to the audience and asked whether there is a current hype in psychedelic research and where we might be in this Hype Cycle. Virtually everyone raised their hands which made it clear there is indeed a hype in the psychedelic field.

Knudsen’s introduction was followed up by Professor David Nutt from Imperial College London who gave an overview of the current state of psychedelics. In brief, he mentioned how psychedelics seem to show efficacy in depression and addiction and shared some of the therapeutic mechanisms of action in the brain, such as alterations in brain connectivity, reduced modularity, and increased neuroplasticity.

Most notably, Nutt shared one of the most recent brain imaging findings of N,N-Dimethyltryptamine (DMT) that were yet to be published. According to Nutt, this work is probably the “most impressive study ever done at our department” as it contains the most comprehensive view of the acute brain action of psychedelics to date. This was made possible through the use of both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to record brain activity before, during, and after the ingestion of intravenous DMT and comparing it to placebo in twenty healthy individuals. In general, the results of the now published study demonstrate that DMT is able to induce network disintegration and desegregation, decreases in alpha power, increases in entropy, altered traveling waves, and global functional connectivity. In other words, a lot is happening during the DMT-experience, and this naturally reflects the peculiar and extraordinary experiences that individuals generally report.

In the evening of March 20^th, directly after the ECNP conference, the results of the study were published in The Guardian reporting how the recordings of DMT reveal a “profound impact across the brain.” One can safely say that this is a clear testament of the hype of psychedelic research and how the media wants to pick up on this latest news.

Nutt further showed yet to be published results from another neuroimaging study that is based on the well-known psilocybin versus escitalopram trial. The team already demonstrated psilocybin-specific effects in the brain last year, such as increases in global integration and decreases in modularity. And now they found more differences between the two substances, namely that escitalopram resulted in a blunted response towards emotional faces. This finding was not demonstrated in the psilocybin condition of the study and further adds to the view that antidepressants seem to blunt people’s emotions.

Finally, Nutt notified the audience of some future policy decisions. This included the statement that US president Biden will make psilocybin and MDMA legal in the next two years and that Australia will reschedule both substances by July 2023.

Animal research: psychoplastogens and affective bias tests

Another prominent subject that has recently entered the field of psychedelic research is the therapeutic use of so-called psychoplastogens. Psychoplastogens refer to a class of substances that are able to rapidly promote neuroplasticity without any hallucinogenic effects. This presentation was given by David Olsen, an associate professor of chemistry, biochemistry and molecular medicine at the University of California, Davis. Olsen is also the co-founder and Chief Innovation Officer of Delix Therapeutics, a company that focuses on the development of psychoplastogens.

As mentioned briefly, psychoplastogens are aimed rapidly promoting neuroplasticity. Olsen mentioned during his presentation that this happens through “transforming the structure of the neuron.” Psychoplastogens establish this transformation in particular through “targeting dendritic spine density and increasing both their growth and complexity.” According to Olsen, a lot of neuropsychiatric disorders are due to a lack of dendritic spine density, hence the recent development of psychoplastogens.

One of the primary psychoplastogen candidates under development is tabernanthalog. This is a novel compound that is structurally similar to the psychedelic drug ibogaine. One study published in Nature in 2020 demonstrated that tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects in rodents. What seems to be very promising is that all this was accomplished without any of the hallucinogenic effects generally observed following the use of ibogaine. Another more recent study found that only a single dose of tabernanthalog was able to promote the regrowth of neuronal connections and restoring functional neural circuits in the brain disrupted by unpredictable stress. This increase in neuroplasticity was accompanied by a correction in behavioural deficits, including anxiety and inflexibility.

But how did the researchers know that the rodents were actually not hallucinating? This was established by using the so-called head-twitch response, which is suggested to be a rodent behavioural proxy for hallucinations induced by 5-HT_2A agonists. But I always wondered: How do we really know? Is the head-twitch response truly representative of hallucinogenic effects? Not surprisingly, one of the audience members asked during a discussion session what actually occurs in rodents during the head-twitch response. As it turns out, when you compare rodents who received 5-MeO-DMT to those who receive tabernanthalog, the former will show a robust head-twitch response, whereas the latter will not.

The discussion continued during dinner on day one with some other attendees and someone hypothesized that rodents not only see through their eyes, but through their whiskers. This sounded very fascinating and, as it turns out, the whiskers of rodents consist of sensory nerves that connect to well-defined structures in the cortex. Indeed, much like humans that use their fingers to navigate the world around, rodents use their whiskers to map out their surroundings and in turn build a 3D picture of the world.

Nevertheless, there are still many difficulties in translating subjective measures from humans to animals, particularly when doing research on depression-like behaviour. This was particularly signified by speaker Emma Robinson, professor of psychopharmacology at the University of Bristol. Nex to the head-twitch response, Robinson presented many other animal testing paradigms, particularly the sucrose preference test, forced swim test, and the novelty seeking test, which are used to assess depression-like behaviour in rodents. She stated that the use of any of these paradigms is suspect to lots of false-positives or false-negatives.

Because of the problems with current animal assays, Robinson and her team used the affective bias test (ABT) as it is suggested to have a better translational validity to humans. Within this assay, animals are trained for a week and have to learn to choose between two options (one positive, one negative) that will in turn reflect a positive or negative bias. It was developed to investigate the hypothesis that the cognitive processes associated with reward-related learning and memory may be modified by affective states. Robinson further explained that this is based on Aaron Beck’s cognitive triad model of depression, a cognitive framework that is often used to account for the negative views and dysfunctional thoughts observed in depression. The research that she presented is not yet published but revealed that one dose of psilocybin or ketamine is able to “completely attenuate the negative bias in rodents.” Translated to humans, this indicates that either psilocybin or ketamine might be able to help individuals with depression mitigate their dysfunctional and negative thoughts. But most importantly, it provides a therapeutic window and opportunity to develop a more realistic view about oneself, the world, and the future.

Drug-Drug Interactions to Increase Therapeutic Efficacy and Improve Harm Reduction

Robinson was followed up by professor of clinical pharmacology and internal medicine, Matthias Liechti, from the University of Basel in Switzerland. Liechti’s presentation was particularly mind-opening to me as he discussed some of the drug-drug interaction effects between psychedelics and other substances. For instance, when individuals with depression receive pre-treatment with the antidepressant escitalopram and then take psilocybin, there were less signs of anxiety and adverse cardiovascular effects. The most striking finding was that this interaction did not alter the psychedelic effects following the ingestion of psilocybin at all. Although this study was quite small with 27 participants and the daily pre-treatment of escitalopram only consisted of 7 days, this finding can be a huge implication for harm reduction in the field of psychedelic research.

Something else that Liechti presented came from an older study that was published in 2015. This study demonstrated that the co-administration of bupropion significantly increased plasma MDMA concentrations and, as a result, prolonged the positive mood effects of MDMA. But maybe even more important, this is another drug-drug interaction that can be used to improve harm reduction during a dosing session due to bupropion’s ability to significantly reduce the heart rate response to MDMA. Together, this indicates that using MDMA with bupropion can enhance mood effects while also lower cardiac stimulation.

Another drug that was mentioned during Liechti’ presentation was ketanserin. Ketanserin has been used in the past to demonstrate that psychedelics primarily target the 5-HT_2A receptor. Indeed, when this drug is taken prior to LSD, ketanserin is able to completely attenuate the subjective effects. But a recent study has now also demonstrated its use for the reversal of the acute response to LSD. Specifically, ketanserin was able to significantly reduce the duration of LSD’s subjective effects from 8.5 hours to 3.5 hours and was able to reduce adverse cardiovascular effects. As such, ketanserin can be “effectively used as a planned or rescue option to shorten and attenuate the LSD experience in humans in research and LSD-assisted therapy.” 

The Neurobiology of Psychedelics and Inter-Individual Heterogeneity

The second day was opened by Katrin Preller, a junior Group Leader at the University of Zurich, and a visiting Assistant Professor at Yale University. She talked about numerous subjects, including the neurobiology of psychedelics, the acute modulation of brain connectivity through psychedelics, and the four current network-level models of psychedelic action (for a full explanation of these models, please continue reading here).

Preller pointed out during her talk that virtually everything we know so far about psychedelics and their effects on the brain is based on averages of a group. This is why she asked the audience “what about inter-individual heterogeneity?” In other words, what about the differences between individuals when we compare them before, during, or after the psychedelic experience? Indeed, not everyone’s brain is exactly the same at the start of a clinical trial and it is something we should consider when evaluating the therapeutic effects of psychedelics. This conundrum led Preller to hypothesize the following, namely that “baseline connectivity is predictive of the acute effects and determines how someone responds to a psychedelic.” This hypothesis is explored further in upcoming papers that are yet to be published.

As a clinical neuropsychologist and someone who conducts neuroimaging research myself, I became very interested in this hypothesis and approached Preller during one of the coffee breaks to ask her how this brain connectivity would look like. She was not able to answer this question in detail because as the research stands, it has not been explored in full yet. I continued to ask whether such connectivity could be used as a marker to determine the dosage of a psychedelic or maybe even the type of therapeutic framework. We know, for example, that high connectivity in the Default Mode Network is associated with a high degree of rumination – one of the salient and important features of in major depressive disorder. Maybe this could in turn indicate the dosage amount and possibly even determine the choice of a specific therapeutic framework, such as Acceptance and Commitment Therapy targeted at increasing psychological flexibility. She partly agreed and reflected that it is particularly important to get a better understanding of the synergistic effects of both psychedelics and therapy that in turn optimize therapeutic outcome. But how brain connectivity can be used for this remains to be explored because we simply need more studies. Similar to how she concluded her presentation, we need to learn more about the brain so we can optimize PAT and prevent cost and frustration with patients.

The Design of Clinical Trials: a European Regulatory Perspective and Music

Nearing the end of the conference we were informed about the challenges regarding the design of clinical trials by Gerhard Gründer, Professor of Psychiatry and Chair of Department of Molecular Neuroimaging at Central Institute of Mental Health, Mannheim. As the research stands today, we have small sample sizes to fails to account for sufficient statistical power, there is a lack of control and difficulty with blinding, and an expectation bias with nocebo effects. These challenges are troublesome, but can be overcome when we conduct more research. Gründer also shared some e-mail messages from participants in order to show that the therapeutic alliance is the most important factor for efficacy and that we should take this into account when conducting trials. 

To help establish the rigorousness of clinical trials with psychedelics, ECNP invited speaker Marion Haberkamp, a current core member of the CNS Working Party (CNSWP) at the European Medicines Agency (EMA), Amsterdam, and a long-time member and now expert of the Scientific Advice Working Party (SAWP). When it comes to psychedelic research, Haberkamp told the audience that “the findings are both intriguing and sobering” but that “we need longer and more trials.”  Accordingly, Haberkamp talked about European regulatory guidelines and challenges that were recently published in the Lancet. As the age-old adage goes in academia, the authors of this paper posit that more rigorous research is needed, but not without giving any specific recommendations. For instance, they added that it is important to reconsider double blinding in clinical trials and the roles of both positive and negative expectancy created during preparatory sessions. Other points include the need to compare psychedelics with psychotherapy, further establish the safety profile of psychedelics, and continue to assess potential drug-drug interactions.

To realise all this, Haberkamp told the audience that there is direct help from the European regulatory office. For instance, researchers are able to come to the SAWP for qualification procedures. Moreover, there are already EMA guidelines for setting up clinical trials for major depressive disorder, substance use disorder, and anxiety. Haberkamp also announced that such guidelines will be available for psychedelics by the summer of 2023.

Patient Perspectives

I want to finale bring attention to Tadeusz Hawrot from PAREA (Psychedelics Access and Research European Alliance). Hawrot is doing a tremendous job in bringing attention to patients’ perspectives, because according to him it is “the patients who are the experts and the most we can learn from.” And this message particularly hit home through the testimony of Dave Pounds, a 59-year-old patient who has been suffering from post-traumatic stress disorder (PTSD) for almost his entire life. A short summary of his story is described down below.

Dave explained to the audience that when he was just a young little boy, he witnessed his mother being raped and murdered at their home. This horrific experience led to the development of recurrent panic attacks in his teenage years and Dave was ultimately diagnosed with PTSD. He tried several types of treatment and an exorbitant amount of different drugs in order to get better, but nothing seemed to work. Even worse, the drugs only seemed to blunt his feelings. A few years ago, he discovered the work of Ben Sessa while Googling on the internet and read about the benefits of MDMA-assisted psychotherapy. He decided to try it out and told the audience about his 1^st experience with MDMA. Dave mentioned first of all how this was all very lucid and completely sober. While on MDMA, he returned to his own bedroom at 12 years old, frozen with fear, knowing what had just happened downstairs. The perpetrator came to his room upstairs, but whilst under the influence of MDMA he was not frightened anymore. His mom was also present in the bedroom, while Dave talked to the perpetrator about how he is going to be punished for what he has done. The most striking part of this story is how his mom turned to the perpetrator, hugged him, and wished him well. This left Dave completely astonished, but it gave him the feeling and conviction that he was able to continue with his life, possibly through the act of forgiveness. Dave further stated that he had a long afterglow while in the hospital and never felt unsafe during his experience. What is more, Dave has developed a so-called MDMA mindset that he can access at will at any time during the day. This has finally brought him warmth and calmness after decades. Dave stated that “it is the best treatment I have had in almost 40 years.” But he is also “frustrated by the lack of governmental acceptance and approval”, as both he, and many others suffering from PTSD, have improved so dramatically after MDMA-assisted psychotherapy. Dave concluded his testimony by saying that stating that “this could be the most profound transformation in healthcare.” There are many profound stories out there like Dave’s that almost seem too good to be true. Right after this testimony, the audience was confronted with the dark side of psychedelics. 

Jules Evans, an academic philosopher and director of Challenging Psychedelic Experiences Project, is aware of the ongoing psychedelic renaissance and many benefits associated with it, but he also acknowledges the various difficulties and challenges associated with psychedelics. This is based on his own personal experience and research with psychedelics. For instance, Evans had his own bad trip at 18 years and developed PTSD and social anxiety after taking LSD with some of his friends. Fortunately, Evans got better after receiving cognitive-behavioural therapy. Evans further gave notice of a bigger survey (n = 10,836) conducted by ICEERS that collected data from more than 50 countries to assess the adverse events following the use of ayahuasca. This survey showed that there is a high rate of adverse physical effects, primarily vomiting (69.9%), and adverse mental health effects (55.9%) in the weeks or months following consumption. Yet, the authors of this paper also concluded that these experiences “are not generally severe, and most ayahuasca ceremony attendees continue to attend ceremonies, suggesting they perceive the benefits as outweighing any adverse effects.” More recently, Evans has conducted an interview study with 30 individuals after a psilocybin truffle retreat in the Netherlands and was able to show that 30% of individuals experienced challenging experiences.

Our very own Joost Breeksema also acknowledges in a recent review of 44 articles that psychedelics are associated with adverse events and that they are probably underreported due to a lack of systematic assessment and sample selection. Yet, this review also stated that challenging experiences can sometimes be therapeutically meaningful and that we should focus on “disentangling truly adverse events from potentially beneficial effects in order to improve our understanding of psychedelic treatments.”

Moving Forward

The amount of knowledge gaps discussed during the conference are manyfold. One message seemed to reverberate through the two days of the ENCP conference – and that is we simply need more research. We need larger studies with more participants and longer follow-ups. Besides this, I went over and compared all my notes from the conference and was able to distil the most prominent knowledge gaps consistent among both speakers and attendees. Here are the three key knowledge that can help move the psychedelic research forward in the upcoming years.

First and foremost, there is the question whether subjective effects are truly responsible for the therapeutic efficacy of psychedelics. Novel psychoplastogens as tabernanthalog developed by David Olsen seem to negate this view. However, the work that has been done so far is based entirely on animal research paradigms, which Emma Robinson pointed out lacks translational validity in humans. It would be interesting to see Olsen and Robinson pair up in order to assess whether the findings still hold up when rodents receive the non-hallucinogenic compound tabernanthalog and are put to the ‘affective bias test’.

Second, our understanding of the neurobiology of psychedelics remains somewhat underdeveloped. Katrin Preller signified this during her talk by pointing out the degree of inter-individual heterogeneity. To reconcile this, we simply need to conduct more studies that are longer and more complex. The multimodal brain imaging study conducted by Imperial College London that assessed the effects of psychedelics before, during, and after a DMT experience using both EEG and fMRI serves as a perfect example of such a study. And we need lots of it.

Third, the investigation of drug-drug interactions, be it the antidepressant escitalopram, bupropion, or ketanserin, show their utility for potential harm reduction and how through pharmacological interaction we could improve psychedelic therapy and outcome. This could have huge implications for how we conduct psychedelic therapy 

The Hype is Real

After the ECNP conference, I can confidently say that “the hype is real” in the field of psychedelic research. Even though the legendary hip-hop group Public Enemy stated that we should not believe the hype, I have garnered only more hype in the form of inspiration, enthusiasm, and realistic optimism. The future for psychedelic research looks promising with lots of different topics to explore and it is truly great that European regulatory committees as the SAWP are involved to help establish rigorous and robust scientific research that will only affirm the validity and credibility of psychedelic-assisted psychotherapy. And we are very fortunate that all this is accompanied by a healthy dose of scepticism by the likes of individuals as Jules Evans. Ultimately, there is enough balance of both yin and yang that can help move the field forward and I am proud to be a part of it.

There were other speakers that I did not mention as this was beyond the scope of this blog post. Despite this, I wanted to clarify here that their talks were greatly appreciated during the conference and have listed their names and credentials down below.

• David E. Nichols, Adjunct Professor at the University of North Carolina, Chapel Hill, NC, is a Distinguished Professor Emeritus at the Purdue University College of Pharmacy. Nichols talked about the basic pharmacology of psychedelics.
• Tomas Palenicek, head of the Psychedelic Research Centre at National Institute of Mental Health, Czech Republic. Palenicek talked about how music genres like psytrance and classic music seem to show the most benefit during psychedelic therapy.
• Jan Raemakers, Professor of Psychopharmacology and Behavioral Toxicology at Maastricht University. Raemakers talked about the feasibility of 5-MeO-DMT in healthy volunteers and individuals with treatment-resistant depression.
• David Erritzoe, Clinical Senior Lecturer and Consultant Psychiatrist at Imperial College London and in CNWL Mental Health NHS Foundation Trust. Erritzoe talked about psilocybin therapy for depression.
• Drummond McCulloch is a PhD who studies the effects of psychedelic drugs on the brain using PET and MR imaging at the Neurobiology Research Unit in Copenhagen. His talk included qualitative data analyses of a clinical trial showing how individuals come more connected to their self, others, and the environment.
• Jaskaran B. Singh, Psychiatry Franchise head at Neurocrine Biosciences. His talk consisted of Industry aspects, precompetitive questions, experience from a related area (esketamine).
• Tiffany Farchione, Director of the Division of Psychiatry in the Office of Neuroscience at FDA. Tiffany’s talk includes regulatory perspectives of the Food and Drug Administration.

We are like islands in the sea, separate on the surface but connected in the deep – William James

One of the most fascinating findings coming from the scientific literature on psychedelics is their ability to drastically alter our beliefs and worldview. These form the basis of how we relate to ourselves, each other, and the world. As a result, they determine how we attach meaning to our lives and whether we ultimately feel happy, sad, or depressed. Our beliefs and worldview can, in short, be considered as one of the most important aspects of who we are and how our lives unfold.

The current prevailing worldview in Western society to which most of us pledge allegiance is that of materialism. I am not referring to materialism in the consumerist sense, wherein the main preoccupation of the human being is the pursuit and obtainment of things, but materialism from the viewpoint of metaphysics, the branch of philosophy that is concerned with the study of the fundamental nature of reality.

Bernardo Kastrup, one of the speakers at ICPR 2022, challenges the current worldview of metaphysical materialism. Specifically, he proposes analytical idealism as an alternative, the notion that reality is essentially mental and inseparable from mind. Bernardo has been leading the modern renaissance on metaphysical idealism for the past ten years and is considered one of the most energetic, diverse, and original thinkers alive today.

The story of how Bernardo came to idealism is truly fascinating. For those who are interested, I highly recommend two podcast episodes (listed below) in which he explains how he arrived at this particular understanding of metaphysics. In short, Bernardo started his career as a computer engineer, working for some of the biggest and most important companies in the world, including the Dutch company ASML, the world’s leading computer chipmaker for the semiconductor industry, and the European Organization for Nuclear Research (CERN) that operates the largest particle physics laboratory in the world (i.e., the Large Hadron Collider).

Despite these prestigious positions, Bernardo always remained a philosopher at heart and was thus concerned with the bigger questions: “What is life? Where do we come from? What happens to our consciousness after we die?” More than anything, he pondered endlessly as a computer engineer on the possibilities and limitations of artificial intelligence: “If you put enough elements of a computer and chips together to aggregate computing power, when will it become conscious? More so, can it become conscious?”

Materialism and The Hard Problem of Consciousness

The unanswered question refers to a notorious problem that has been troubling scientists and philosophers alike for decades. It was first coined as ‘The Hard Problem of Consciousness’ by Australian philosopher David Chalmers in his famous essay Facing Up to the Problem of Consciousness, which has been declared as the second most important unanswered question in science by Science. According to Bernardo, it should have been number one. 

Before we continue, let’s first briefly discuss what materialism is all about. This way we can better comprehend the Hard Problem.

Metaphysical materialism states that all of reality is composed of a small set of fundamental subatomic particles, which are described in the ‘Standard Model’ of particle physics. These particles are the basic building blocks of nature and responsible for the character and behaviors of all known phenomena, from the chair you are sitting on to the entirety of the Milky Way, to your body and loved ones, and of course your mind.

Materialism assumes that these subatomic particles are “dead” and, therefore, absent from consciousness. Now here is the rub: “How do you eventually get consciousness simply by arranging ‘dead’ subatomic particles together?” Alas, we have arrived at the Hard Problem of consciousness. Bernardo calls it a sore on the foot of materialism. In fact, it is such an obstinate problem that materialist philosophers, such as Daniel Dennett, have been accused of ‘explaining it away’.

How do you eventually get consciousness simply by arranging ‘dead’ subatomic particles together?

Other famous neuroscientists, such as Christof Koch, remain hopeful and claim that it is only a matter of time before we resolve the Hard Problem. Koch initiated his quest alongside molecular biologist turned neuroscientist and Nobel Prize winner Francis Crick in the 1990s. Most of all, their primary objective was to discover the neural correlates of consciousness (NCCs), which refers to the “the minimum neuronal mechanisms jointly sufficient for any one specific conscious experience.” 

Similar to philosopher Daniel Dennett, consciousness has in their view a mechanistic basis and is ultimately a scientifically tractable problem. So long as we keep collecting more data about the inner workings of the brain through state-of-the art neuroimaging techniques and aggregate this over the years, we will eventually find the much sought after NCCs. The phenomenon of consciousness is, after all, produced by an assembly of dead subatomic particles that we would call a human brain. Consciousness is material brain processes at work.

Exactly how these material brain processes and the various mechanical movements of particles are accompanied by inner life remains, however, “a question left unanswered by materialism”, states Bernardo in Why Materialism is Baloney – How true skeptics know there is no death and fathom answers to life, the universe and everything.

It is here that Bernardo firmly states that such (scientific) pursuits are – and will remain – futile. We cannot solve the Hard Problem through science because of the simple fact that science cannot look at what nature is – science can only look at what nature does: “The scientific method allows us to study and model the observable patterns and regularities of nature […] But our ability to model the patterns and regularities of reality tells us little about the underlying nature of things”, writes Bernardo.

Tackling the Hard Problem: Idealism to the Rescue

To tackle the Hard Problem, we need to approach it through metaphysics, it being the branch of philosophy that concerns itself with the study of the fundamental nature of reality. Metaphysics looks at what nature is.

Now, Bernardo does not actually “solve” the Hard Problem, but rather circumvents it through his metaphysical framework of idealism. In fact, he suggests that there is no problem at all; it is only a problem when we believe the metaphysics of materialism to be true. And so long as we adhere to the materialist worldview, we keep misconstruing our conception of reality through a flawed conceptual framework that is ultimately nonsensical and self-defeating.

As I was reading about the Hard Problem and delved more and more into the framework of idealism, a quote from Einstein came to mind that perfectly encapsulates the current predicament: “We cannot solve our problems with the same thinking we used when we created them.” Within the metaphysical framework of materialism, the Hard Problem cannot possibly be solved. It is created within a certain mode of thinking, a mode of thinking that is, according to Bernardo, the wrong one.

The Hard Problem is only a problem when we believe the metaphysics of materialism to be true.

So what, then, is idealism? As mentioned before, idealism consists of the notion that mind and reality are inseparable. Put slightly differently, it states that ‘mind’ is the medium of reality, not ‘matter’. This sounds rather abstract and confusing at first, because mind is generally referred to as something we use (although I have my doubts about some individuals) or lose. We see this particularly reflected in our everyday language: “use your mind for once!” or “he has lost his mind!”

Within the metaphysical framework of idealism, however, the mind is defined as something entirely different. In the opening of Chapter 3 in Why Materialism is Baloney, Bernardo provides a “most natural and obvious answer” to the question of what ‘mind’ signifies within the framework idealism: “Mind is the medium of everything that you have ever known, seen, or felt; everything that has ever meant anything to you. Whatever has never fallen within the embrace of your mind, might as well have never existed as far as you are concerned. Your entire life and universe – your parents and the people you love, your first day at school, your first kiss, every time you were sick, the obnoxious boss at work, your dreams and aspirations, your successes, your disappointments, your worldview, etc. – are and have always been phenomena of your mind, existing within its boundaries.”

Yet this description of mind within the framework of idealism remains just that: a description. Again, I want to emphasize here that in order to intuitively understand, or “grok” (to borrow from Bernardo’s lexicon), requires a different mode of thinking. Speaking from personal experience, this is an arduous process, particularly because the worldview of materialism is so firmly ingrained within us. It is a firmly established belief system accompanied by a habitual mode of thinking that is often considered infallible.

Mind is the medium of everything that you have ever known, seen, or felt; everything that has ever meant anything to you. Whatever has never fallen within the embrace of your mind, might as well have never existed.

To avoid eating the menu, we can use metaphors to get an initial taste of idealism. Fortunately, Bernardo provides no shortage of these in Why Materialism is Baloney – a triumphant feat on par with the wit of Alan Watts. In my view, the most intuitive analogy to start off with when trying to “grok” idealism is the whirlpool.

Whirlpools Within the Lake of Mind

Consider ‘mind’ as a lake of water. When this lake is still, water is flowing along freely without any hindrance. The water is not localized. Now, imagine a small whirlpool within the lake. All of a sudden, there is an identifiable pattern that assembles the water molecules in place within the lake. In other words, the whirlpool reflects a pattern that localizes the flow of water (see Figure 1).

We are able to point at this pattern and say: “Here is a whirlpool!” Other water molecules that are not localized through the whirlpool are ‘filtered out’ – they are kept away by the particular dynamics of the whirlpool. From this, Bernardo makes two observations regarding the whirlpool metaphor, namely that 1) the whirlpool reflects a localization of water within the lake and 2) that there is a ‘filtering out’ of the other remaining water molecules.

Figure 1
The whirlpool in a lake is a metaphor for a brain in the medium of mind (from Kastrup, 2014)

These observations lead to the following conclusion, namely that “there is nothing to the whirlpool, but the lake itself.” It is important to remember this statement in the next few paragraphs, because it contains the essence of idealism. Once more, the only thing that the whirlpool reflects is a very specific pattern of water that has been localized within the lake. Ultimately, it is all water. It is all one.

There is nothing to the whirlpool but the lake itself.

Bernardo mentions the brain as something very analogous to the whirlpool in the lake. More specifically, he talks about the brain as “an image [pattern] in mind, which reflects a localization of contents of mind.” And just like there is nothing to the whirlpool but the lake, there is nothing to the brain but mind itself. Within the metaphysics of idealism, the brain represents an identifiable pattern of the localization of mind. Similar to the whirlpool within the lake, we can point to the brain within the medium of mind and say: “Here is a brain!” And just as the whirlpool captures water molecules from the lake, the brain assembles subjective experiences from the medium of mind and ‘filters out’ experiences of reality that under ordinary circumstances do not fall within its boundaries.

There is nothing to the brain but mind itself.

Consider the following. Would you say that a whirlpool causes water? Or that flames are the cause of combustion? What about lightning being the cause of electric discharge? My guess is probably not. In fact, you would be rather perplexed when someone gives you these presuppositions: “Of course a whirlpool does not cause water. It is exactly the other way around; the water, or the lake, is the very thing that causes the whirlpool!” Naturally, the whirlpool and water are very much related to each other, but the whirlpool only represents a “partial image” of the whole process that is lying underneath it.

And the same can be said of the brain. It too represents a partial image within the broader medium of mind. According to Bernardo, saying that “the brain generates mind is as absurd as to say that a whirlpool generates water!” (italics added).

Understanding the brain to be a partial image within the broader medium of mind eliminates the Hard Problem entirely, because the aforementioned NCCs can now be interpreted differently. Yes, there still exists a clear and obvious relationship between brain states and someone’s state of ‘mind’, but now the former can be seen as a partial image of the latter. As Bernardo concludes: “The brain is an experience, an image in mind of a certain process of mind.”

What materialism is trying and claiming to accomplish is the impossible. It maintains that the brain is the very thing that causes consciousness and the plethora of subjective experiences that go along with it. But if you understand just a little bit of what has been presented so far, you can begin to see that this is a complete non sequitur. It does not follow that consciousness is the cause of brain processes, as one would similarly not infer that combustion and water are respectively caused by flames and whirlpools. Trying to fix it only results in what is keenly illustrated on a subreddit that creates some hilarious memes of Bernardo and idealism.

Of course, it would be unfair to entirely negate materialism based on just this metaphor, albeit it being a very useful one. This is where psychedelics come in, as their effects on the brain help make sense of this metaphor.

Brief Peeks Beyond: The Acute effects of Psychedelics on the Human Brain

In the past decade, Bernardo has written extensively about the acute effects of psychedelics on the human brain. More specifically, he has provided evidence of how neuroimaging studies seem to support the tenets of idealism – much to the dismay of other materialist neuroscientists, which include previous ICPR speakers as Enzo Tagliazucchi and Robin Carhart-Harris.

To be clear, Bernardo never suggested “malicious intent.” Rather, the intention was to emphasize how “paradigmatic expectations can make it all too easy to cherry-pick, misunderstand and then misrepresent results so as to render them consistent with the reigning [materialist] worldview.” Indeed, it is a clear example of how materialism permeates the culture and how unaware we are of our philosophical presuppositions.

In general, neuroimaging studies examining the acute effects of psychedelics on the human brain demonstrate that there is an inverse relationship between brain activity and subjective experience. Wait, what? Yes, you read that correctly. Psychedelic substances are found to reduce brain activity, rather than increase it. Such results vehemently oppose the intuitions of materialism. After all, it is brain activity itself that is supposed to constitute subjective experience: “consciousness is brain activity.” How else are we going to find the NCCs?

Down below follows a summary of two important neuroimaging studies and Bernardo’s interpretations of their results, which led him to conclude that the evidence thus far supports idealism.

The first study examined the neural correlates of psilocybin. According to Bernardo, this study was “extremely well designed” as it countered the “uncertainties of measuring brain activity with an fMRI scanner.” Here, he is alluding to the fact that the researchers used two ‘signals’ in determining brain activity, namely arterial spin labeling (ASL) and blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). More specifically, ASL is a non-invasive fMRI technique for measuring cerebral blood flow (CBF): the amount of CBF indicates the amount of brain activity. On the other hand, BOLD measures the difference between oxygenated and deoxygenated blood in various brain regions that indicates the level of metabolism. Ultimately, it is the amount of metabolism which indicates the amount of brain activity in a given brain region.

With both these measures, here is what the authors from the psilocybin study reported: “we observed no increases in cerebral blood flow in any region” (italics added). Even more ‘alarming’: “the more the drug deactivated the brain, the more intense were the subjective experiences reported by the subjects” (italics added).

Reading further into the study, results become particularly worrisome for materialists when study participants made report of having had extremely rich subjective experiences, which included “geometrical patterns”, “extremely vivid imagination”, “seeing their surroundings change in unusual ways”, and having experiences that feature a “dream-like quality.”

Bernardo summarized the findings in one of his many blog posts and stated: “the brain largely goes to sleep. Who, then, is having the trip? It doesn’t seem to be the brain.”

Neuroimaging studies examining the acute effects of psychedelics on the human brain demonstrate that there is an inverse relationship between brain activity and subjective experience

Fast forward four years later and another study came out that examined the neural correlates of LSD. This time the findings received much more attention from the public and was covered by prestigious media outlets, such as The Guardian and CNN. Bernardo responded to this “fanfare” and explained to his readers how they are being “subtly deceived (again).” Because, similar to the psilocybin study, results yet again demonstrated observed reductions of brain activity across the entire brain (see Figure 2). As you can clearly see, there is a whole lot of blue. In fact, everything is blue which indicates reductions in brain activity.

Now, to be fair, the authors from the LSD study did find one small inconsistency when comparing findings to the psilocybin study. Apparently, there were results that indicated increases in CBF in the visual cortex of the brain when LSD was compared to placebo (see third row Figure 3). Such a finding would indeed support the view of materialism, i.e., more activity in the brain equals more subjective experience.

Figure 2
Brain activity as determined by magnetoencephalography

Yet, the authors from the LSD study concluded that the observed localized increases in CBF were possibly the result of measurement artifacts: “one must be cautious of proxy [indirect] measures of neural activity (that lack temporal resolution), such as CBF or glucose metabolism, lest the relationship between these measures, and the underlying neural activity they are assumed to index, be confounded by extraneous factors, such as a direct vascular action of the drug.”

Figure 3
Cerebral blood flow as determined by ASL

This is why the authors opted to put more emphasis on findings from Figure 2, as it represents the results of magnetoencephalography (MEG). This is another widely used functional neuroimaging technique for mapping brain activity. As opposed to indirect measures such as BOLD and ASL, MEG represents a direct measure of neural activity. Naturally, the LSD study authors concluded that MEG: “should [thus] be considered [as] more reliable indices [measures] of the functional brain effects of psychedelics” (italics added).

Of course, these were only two studies that examined the acute effects of psychedelics on the brain. But as many of you probably know, the psychedelic renaissance has been on full throttle in the past years. As both Bernardo and Prof. Edward F. Kelly alluded to in an opinion piece on Scientific American: “these unexpected findings have since been repeatedly confirmed with a variety of psychedelic substances and various measures of brain activity” (see 2013, 2015, 2016, and 2017). 

Let us now transpose these neuroimaging findings in context of the whirlpool metaphor. Remember how we said that both the whirlpool and brain analogously represent an identifiability pattern, or image, within the broader medium of the lake and mind, respectively? And remember how we also said how they both reflect a localization and filtering of the contents of mind, which led us to conclude that there is nothing to the brain but mind itself? Here is what psychedelics seem to do.

Psychedelics perturb the dynamics of the brain to such a degree that there is a non-localization of the contents of mind (i.e., subjective experiences that are, under ‘normal’ circumstances, assembled by the brain). But now, by bringing psychedelics into the mix, subjective experiences from the medium of mind are suddenly no longer filtered out. The whirlpool stops existing, water molecules are able to flow along freely, and thus become one with the lake. Analogously, the brain stops “existing” as activity goes down that results in a bombardment of subjective experiences (e.g., “extremely vivid imagination” as the psilocybin study participants reported). Ultimately, the contents of mind that were, under ‘normal’ circumstances, assembled by the brain become one with the medium of mind. To put it in Aldous Huxley’s words, the psychedelic experience can bring about the realization that “each one of us is potentially ‘Mind at Large’.” 

The contents of mind that were assembled by the brain become one with the medium of mind

A sweet moment of irony, particularly for Bernardo, is how the authors from the psilocybin study unintentionally hinted toward the whirlpool metaphor themselves by mentioning Aldous Huxley’s metaphor of the reducing valve: “This finding is consistent with Aldous Huxley’s ‘reducing valve’ metaphor … which propose[s] that the mind/brain works to constrain its experience of the world.”

For people who are unaware, the reducing valve metaphor is a result of Huxley’s experience with the psychedelic substance mescaline. He reported his experiences in The Doors of Perception and Heaven and Hell. Huxley’s description of the brain as a reducing valve – and its similarities with the whirlpool metaphor – become immediately apparent in the following passage: “The suggestion is that the function of the brain and nervous system and sense organs is in the main eliminative and not productive (italics added). Each person is at each moment capable of […] perceiving everything that is happening everywhere in the universe. The function of the brain and nervous system is to protect us from being overwhelmed […] by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful.” To clarify here, when Huxley mentions that the brain’s job is “to protect us from being overwhelmed” seems to be analogous to the localization of the contents of mind. The same can be said for how subjective experiences are “shut out” and the filtering out process in the whirlpool metaphor.

Finally, these so-called peak experiences associated with psychedelics are not only reserved to dedicated psychonauts. In fact, “there is a broader pattern associating peak subjective experiences with reduced blood flow to the brain”, says Bernardo. This is further exemplified in Why Materialism is Baloney and another academic article in which he lists a host of findings from different domains (e.g., hyperventilation, meditation, gravity-induced loss of consciousness, cerebral hypoxia, cardiac arrest, and even brain damage). All seem to corroborate the phenomenon that less blood flow equals richer subjective experiences, not less.

Ego Death: Becoming One With the Medium of Mind

What I find is the earlier observation and remark that the brain, for a brief period, stops “existing.” I am alluding here to a widely studied phenomenon in the psychedelic literature referred to as ego death, or ego dissolution.

The experience of ego death consists of an altered state of consciousness in which there is a dramatic breakdown of one’s “sense of self.” Several neuroimaging studies have consistently demonstrated that psychedelics reliably facilitate this breakdown, something that occurs through the disintegration of an important brain network called the Default Mode Network (DMN) (see 2015, 2019 and 2020). The DMN is regarded by some neuroscientists to represent the neural correlates of the self or ego, as increased brain activation is primarily seen during self-referential processing. 

Bernardo interprets the neuroimaging findings in the context of idealism by using the whirlpool metaphor: “I couldn’t help but visualize the deactivation of the ego functions as analogous to someone inserting one’s hand in a whirlpool, disrupting the ‘loopy’ flow that maintains it, and thereby allowing the water molecules originally trapped in it to escape.” Within this metaphor, the hand represents psychedelics that perturb the dynamics of the brain and how it dissolves the sense of self, or ego, through disintegration of the DMN.

We have read before that study participants report “geometrical patterns” and experiences of “dream-like quality.” What else do they report during a psychedelic peak experience? More importantly, what do they report when experiencing ego death, or ego dissolution, once their DMN disintegrates? Lots of anecdotal reports can be found from the Erowid experiences vault, but these might not be considered as reliable or valid. Fortunately, there also are findings from clinical trials.

One such study was conducted by the Imperial College London. This trial’s primary objective was to investigate if psilocybin was effective in helping people overcome their treatment-resistant depression. This consisted of a group of 12 people who were seriously depressed, some of which “have had a depression for an average of 18 years and tried between three and eleven antidepressant medications and up to six courses of talking therapy and none of which had helped them.” With a response rate of 67% (N = 8) only one week after treatment, and another 42% (N = 5) of individuals who remained in remission (symptom-free) after three months, the results of this study were extraordinary, particularly considering the tenacity of the participants’ depression and after receiving only two oral doses of psilocybin.

Six months later, the study participants were interviewed by one of the research team’s clinical psychologists Dr. Rosalind Watts. She asked them a series of questions to assess patient experiences during the psilocybin sessions, including the million dollar question: “What happened during dosing?” I refer the reader to the article itself or to watch Watts’ presentation to prevent you from becoming overflowed by tedious and superfluous amounts of awesome quotes. Down below I have listed some of the most revealing descriptions that seem to correspond with the whirlpool metaphor and idealism.

In an entire paragraph devoted to the ‘Connection of a spiritual principle’, Watts describes what happened during the psilocybin session. Here, patients frequently report “strong feelings of compassion, love, and bliss” that were often beautifully put, almost poetically. For instance, one of the participants stated that during the dose: “I was everybody, unity, one life with 6 billion faces, I was the one asking for love and giving love, I was swimming in the sea, and the sea was me.” This is a particularly clear example that corresponds with the metaphor of the whirlpool, as the participant literally mentions how she was swimming in the sea and realized being a part of it.

Another report hits the nail on his head by exemplifying this transition: “Before I enjoyed nature, now I feel part of it. Before I was looking at it as a thing, like TV or a painting. You’re part of it, there’s no separation or distinction, you are it” (italics added). Other participants reported similar experiences during the dose, such as “connecting to all other souls” or that it “felt like sunshine twinkling through leaves, I was nature” (italics added). 

I was everybody, unity, one life with 6 billion faces, I was the one asking for love and giving love, I was swimming in the sea, and the sea was me

In general, the reports seem to follow a common narrative, namely that they are part of something greater than their little ‘selves’. Study participants as whirlpools have become one with the medium of the lake again. We can even be bold to suggest that these participants realized that they were “nothing to the whirlpool, but the lake itself.”

Analogously, the ego and the sense of self stops existing, as the DMN disintegrates and the contents of mind become one with the medium of mind. The great philosopher Alan Watts provides the quintessential description: “We do not ‘come into’ this world; we come out of it, as leaves from a tree. As the ocean ‘waves,’ the universe ‘peoples’. Every individual is an expression of the whole realm of nature, a unique action of the total universe” (italics added).

Future Musings and Grokking Idealism

As mentioned in the introduction, our view of the world determines in large part how we relate to ourselves, others, and the world. Now, if we maintain that the metaphysics of idealism is true – and we are indeed all whirlpools of the same lake – consider first how this will affect your life and how you will behave to your fellow human beings. Bringing hurt to someone else would then literally mean bringing hurt to oneself.

But I think the implications of idealism go much further than this. In fact, idealism made me think a lot about what Carl Sagan alluded to in his brilliant TV series Cosmos: A Personal Voyage: “a new consciousness is developing which sees the earth as a single organism and recognizes that an organism at war with itself is doomed.” And this is what idealism does – it recognizes that we are all, in Huxley’s words, potentially Mind at Large.

This has led me to ask two fundamental questions that hopefully can be answered in the near future. Might the metaphysical framework of idealism result in a significant reduction of unnecessary conflict and suffering in the world as it sees that we are all connected? And what important role do psychedelics play in facilitating this worldview?

The possible transition of materialism to idealism will probably take some time. In part, this is because it is extremely difficult to intuitively understand, or “grok”, idealism. This inability is exacerbated through our cultural milieu that always rejoices in the viewpoints of materialism: “we grew up to believe that mind is a product of the brain, not the other way around”, says Bernardo. As a result, it has been imprinted in our very way of being and can be considered as the lingua franca of contemporary metaphysics. It is the exact reason why Bernardo provides some solace to his readers through the advice of giving all this some thought to let the metaphysics of idealism sink in.

Indeed, the drastic change in worldview does not come naturally to us. It requires what is coined by renowned philosopher of science Thomas Kuhn a paradigm shift – a fundamental change in the basic concepts and experimental practices of a certain discipline. What is more, we are protected by ourselves from what is referred to as an “ontological shock.” This happens particularly when beliefs are diametrically opposed to prior held personal, religious, or spiritual beliefs – something that OPEN director Joost Breeksema and neuroscientist Michiel van Elk refer to in Working with Weirdness.

Bringing it all together, I believe we are at the precipice of another Copernican revolution and that Bernardo represents a modern day version of Giordano Bruno. Bruno was a 16^th century philosopher tried for heresy by the Roman Inquisition and subsequently burned at the stake for his cosmological theories (e.g., stars were distant suns surrounded by planets). Such ‘theories’ are now considered common knowledge, and more importantly, common sense. Only centuries later, Bruno has been characterized as a martyr for science. Might the same be said of Bernardo? Possibly so, as in his own words, “future philosophers will be merciless at our stupidity.” Let us not “burn” him at the stake, for Bernardo’s thoughts too can one day become common sense.

Dr. Bernardo Kastrup will give his presentation titled Psychedelic effects are one piece of a much bigger puzzle on Saturday September 24^th at ICPR 2022 in the Philharmonie, Haarlem.

Bio
Bernardo Kastrup is the executive director of Essentia Foundation. His work has been leading the modern renaissance of metaphysical idealism, the notion that reality is essentially mental. 

He has a PhD in philosophy (ontology and philosophy of mind) and another PhD in computer engineering (reconfigurable computing, artificial intelligence). As a scientist, Bernardo has worked for the European Organization for Nuclear Research (CERN) and the Philips Research Laboratories (where the ‘Casimir Effect’ of Quantum Field Theory was discovered). 

Formulated in detail in many academic papers and books, his ideas have been featured on Scientific American, the Institute of Art and Ideas, the Blog of the American Philosophical Association and Big Think, among others. Bernardo’s most recent book is Science Ideated: The fall of matter and the contours of the next mainstream scientific worldview. For more information, freely downloadable papers, videos, etc., please visit www.bernardokastrup.com.

Podcast appearances
Jaimungal, C. (Host). Bernardo Kastrup on Analytical Idealism, Materialism, The Self, and the Connectedness of You and I [Video]. YouTube. https://www.youtube.com/watch?v=lAB21FAXCDE
Kieding, J. (Host). (2021, June 15). Bernardo Kastrup — The Man Behind the Ideas: Identity, Truth, Philosophy, and Psychotherapy [Video]. YouTube.  https://www.youtube.com/watch?v=jylqAohnzRY

Common misconceptions
There are several misconceptions about idealism (listed below). For this I refer the reader to pages 64 to 69 in Why Materialism is Baloney:
1. Idealism is not solipsism;
2. Idealism is not panpsychism;
3. Falling back into realist assumptions: “where is this mind stuff?”
4. Why can’t we influence reality at will if everything is in mind?