In recent years, psychedelics like psilocybin and LSD have gained significant attention for their potential to treat neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD), depression, post-traumatic stress disorder (PTSD), and addiction ¹. This shift in perspective is leading to increased acceptance among psychotherapists and psychiatrists, paralleling the clinical use of esketamine. Concurrently, there is a growing interest in understanding the mechanisms by which psychedelics and their analogues exert their effects, with the goal of designing novel neuropharmaceuticals ².

Mechanisms of Action

Psychedelics primarily act through the serotonin receptor 5-HT2A, which activates both Gαq/11 and β-arrestin2 pathways (Figure 1.). However, it is still unclear which of these pathways is more critical for the therapeutic effects. Recent studies have shown that hallucinogenic psychedelics (e.g., psilocybin) and non-hallucinogenic psychedelics (e.g., Tabernanthalog, or TBG) may differentially activate these pathways ³. This differential activation can lead to changes in chromatin states at gene enhancers involved in synapse organization and neuronal plasticity ⁴.  Despite these findings, significant gaps remain in our understanding of the cellular and neural mechanisms linking psychedelic-induced synaptic plasticity to behavioral outcomes. Additionally, it is unknown whether non-hallucinogenic psychedelics promote plasticity through the same mechanisms ⁵.

Figure 1. Biased signaling of 5-HT2AR: Gq- dependent and beta-arrestin dependent. nhP: non-hallucinogenic Psychedelics; hP: hallucinogenic Psychedelic.

Psychoplastogens: A New Class of Compounds

Psychoplastogens are substances capable of rapidly inducing structural and functional neuronal plasticity, which can modulate cognitive functions. These compounds may help rescue neuronal atrophy seen in many neuropsychiatric and neurodegenerative disorders by modulating neurotrophic factor expression, activating neuronal repair mechanisms, and mediating immune responses. The therapeutic potential of these compounds has been increasingly recognized, emphasizing the need to investigate existing natural compounds before embarking on the lengthy process of synthesizing new ones. This approach could leverage existing knowledge and reduce the costs associated with developing new substances ⁶.

Differentiating Psychedelics

Psychedelics are a family of psychoactive substances that induce altered states of consciousness, profoundly changing thoughts, emotions, and perceptions. They are distinct from other psychoactive compounds such as cannabinoids (e.g., THC), entactogens (e.g., MDMA), and dissociatives (e.g., ketamine). Despite strict regulations and illegality in many countries, there is a need to develop new psychedelic-based therapeutics with optimized pharmacological profiles to ensure safety and efficacy ⁷.

Psychedelics can be chemically classified into three main types: tryptamine analogues, ergoline derivatives, and phenethylamines.

Tryptamine Analogues

These compounds share the structural backbone of serotonin. Psilocybin and DMT are notable examples. Psilocybin, found in “magic mushrooms,” is converted in the body to its active form, psilocin, which produces mind-altering effects. DMT induces rapid and intense psychedelic experiences but has a short duration of action. It is necessary to balance the therapeutic potential with the strong hallucinogenic effects for clinical use.

Ergoline Derivatives

LSD is the primary example of this class, known for its potent hallucinogenic effects. Research is ongoing to develop non-hallucinogenic derivatives that can provide therapeutic benefits without the intense psychedelic experiences.

Phenethylamines

Mescaline, derived from certain cacti, is a key compound in this class. It produces visual and auditory hallucinations and has been studied for its potential therapeutic effects ⁷.

Non-Hallucinogenic 5-HT2AR Agonists

The therapeutic effects of psychedelics are often believed to be coupled with their hallucinogenic properties. However, preclinical evidence suggests that these effects can be separated. This raises an important question: how can we preserve the therapeutic benefits of psychedelics while minimizing or eliminating the hallucinogenic effects? A limited number of non-hallucinogenic 5-HT2A agonists have been identified. For example, 6-F-DET, a tryptamine analogue, lacks hallucinogenic effects but also has weak functional activity. Ergoline derivatives such as 2-Br-LSD and lisuride have shown potential for treating depression and other psychiatric disorders in animal studies, though lisuride has induced hallucinations in some patients with Parkinson’s disease ⁷.

IsoDMT derivatives, introduced in the 1980s, represent another group of non-hallucinogenic 5-HT2A agonists. Compounds like isoDMT and 5-OMe-isoDMT have been identified as non-hallucinogenic through drug discrimination tests. Recent studies by the Olson group have reported a series of isoDMT compounds that promote neuronal growth and have significant antidepressant effects in mouse models, presenting significant interest as psychoplastogens for clinical applications ⁸. One such compound, AAZ-A-154, has shown promise as a non-hallucinogenic psychoplastogen. Another compound, TBG, a simplified analogue of ibogaine, has been found to increase dendritic arborization and spine density in rat cortical neurons.

Future Directions and Clinical Applications

The potential to repurpose psychedelics for treating not only cognitive disorders but also neurological conditions characterized by neuronal atrophy is growing. However, substantial research is still needed to elucidate how these compounds stimulate neuroplastic mechanisms. It is crucial to determine the developmental stages at which treatment is most beneficial and understand how these compounds affect neuronal networks at different scales ⁹.

From a medicinal chemistry perspective, there is an urgent need to develop new chemical entities with optimized pharmacological profiles to create more effective and safer psychedelic-based therapeutics. This includes supporting research on 5-HT2A receptor agonists for use in various disorders, starting with antidepressants. Disturbances in 5-HT2A receptor signaling are well-known to be implicated in mental disorders such as schizophrenia, depression, anxiety, and addiction.

Advanced techniques are being developed to thoroughly investigate the hallucinogenic properties of psychedelics. These include novel recombinant receptors and optimized functional assays that help understand the molecular mechanisms underlying the therapeutic effects of psychedelics. As these compounds move towards clinical trials, it is essential to develop and use appropriate preclinical models that can accurately measure their hallucinogenic behaviors. While translating findings from rodents to humans is challenging, behavioral assays like the Head-Twitch Response (HTR) have been developed to distinguish between hallucinogenic and non-hallucinogenic psychedelics in vivo. ⁷

Conclusion

There is a growing space for the therapeutic use of psychedelic compounds, which can potentially be applied to both cognitive and neurological disorders characterized by neuronal atrophy. However, a considerable amount of research is still needed to fully understand how these compounds stimulate neuroplasticity and determine the most effective stages for treatment. This knowledge will help in developing new therapies that can effectively manipulate neuronal networks and provide significant benefits for a range of brain conditions.

References

1. Mastinu, A. et al. The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology. IJMS 24, 1329 (2023).
2. Lowe, H. et al. Psychedelics: Alternative and Potential Therapeutic Options for Treating Mood and Anxiety Disorders. Molecules 27, 2520 (2022).
3. Wallach, J. et al. Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential. Nat Commun 14, 8221 (2023).
4. Cameron, L. P. et al. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 589, 474–479 (2021).
5. De La Fuente Revenga, M. et al. Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice. Cell Reports 37, 109836 (2021).
6. Benko, J. & Vranková, S. Natural Psychoplastogens As Antidepressant Agents. Molecules 25, 1172 (2020).
7. Duan, W., Cao, D., Wang, S. & Cheng, J. Serotonin 2A Receptor (5-HT _2A R) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chem. Rev. 124, 124–163 (2024).
8. Dong, C. et al. Psychedelic-inspired drug discovery using an engineered biosensor. Cell 184, 2779-2792.e18 (2021).
9. Saeger, H. N. & Olson, D. E. Psychedelic‐inspired approaches for treating neurodegenerative disorders. Journal of Neurochemistry 162, 109–127 (2022).

Meet Rick Strassman

Join us for an exciting Q&A session with Dr. Rick Strassman, where we’ll delve into the fascinating realms of consciousness exploration, psychedelic research, and innovative DMT trials. Gain exclusive insights into Dr. Strassman’s groundbreaking work and have your burning questions answered live. Can’t make it? Don’t worry! The recording will be accessible to all members of our open community. Reserve your spot now by clicking here and embark on a journey of discovery with one of the foremost pioneers in psychedelic research.

Author of DMT – The spirit molecule & The Psychedelic Handbook

We are honoured to delve into the realms of consciousness exploration, clinical psychedelic research and innovative DMT trials together with the author and psychiatrist Dr Rick Strassman. Most people will associate his name with his bestselling publications, such as “DMT – The Spirit Molecule: A Doctor’s Revolutionary Research Into the Biology of Near-Death and Mystical Experiences”, and “The Psychedelic Handbook: A Practical Guide to Psilocybin, LSD, Ketamine, MDMA, and Ayahuasca”. 

In this blog, we’ll touch on some chapters of the life and work of Dr. Strassman, from his academic pursuit with psychedelic substances to his profound insights into the innovative therapeutic models of DMT administration. Ultimately, the following article aims to introduce you to some of Dr Strassman’s earlier and current work with a special focus on N,N Dimethyltryptamine (DMT), the active component of ayahuasca. If you’re eager for further insights and have burning questions for Dr. Strassman, don’t miss the chance to participate in our upcoming online Q&A session. 

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Disclaimer: 

This blog post is not dedicated to providing an exhaustive and elaborate description of Strassman’s biography, but rather aims to shed light on some of his important scientific endeavours, and spiritual journeys to prepare and facilitate an interesting OPEN Q&A session with Rick Strassman!

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Dr. Strassmans Background and Earlier Career

Strassman’s journey begins in 1952 in the vibrant city of Los Angeles, California. His academic background started with his undergraduate studies in zoology at Pomona College in Claremont California, after which he transferred to Stanford University. Soon after in 1973, he graduated with departmental honors in biological sciences. 

The next chapter of Dr Strassman’s journey unfolded at the Albert Einstein College of Medicine of Yeshiva University in the Bronx, New York, where he obtained his medical degree with honours in 1977. This pivotal moment set the stage for a career that would seamlessly blend academic rigour with spiritual exploration and scientific inquiry.

Continuing his career at the University of California, Davis Medical Center, he completed his general psychiatry residency, earning acclaim with the prestigious Sandoz Award for outstanding graduating resident in 1981. His subsequent work took him to the rugged landscapes of Fairbanks, Alaska, and the vibrant community of Albuquerque, New Mexico, where his research group were the first to document the role of melatonin in humans. Melatonin is secreted by the pineal gland in the human brain and plays an important role in sleep by setting and regulating the inner human clock (scientifically referred to as the circadian rhythm). Publically, his work is sometimes reduced to his important role as an author and his involvement in the first DMT research after the “War on Drugs”. However, it is important to understand Strassman’s early work because it played an important role in pursuing his future endeavours. Consequently, before zooming in on his work with psychedelics, I will briefly dedicate the next paragraph to acquaint you with some of his experience, study and practice in the world of religion and spirituality.

Religious and Spiritual Journey

Beyond academia, Dr. Strassman’s journey took him on a deeply personal and spiritual odyssey. He grew up in a Conservative Jewish home and underwent his bar mitzvah ritual. Following this, he ceased any formal affiliation or study within Judaism. His spiritual journey therefore begins with the practice of transcendental meditation during college. Located on the West Coast during the ’60s and early ’70s, Strassman was fortunate to be at the right place at the right time for taking a deep dive into the world of mindfulness meditation, Eastern religions and psychedelics. 

Several years after his initial college experience with meditation, the psychiatrist commenced the deeper study and practice of Soto Zen Buddhism under the supervision and guidance of a Western Zen order. This practice was rewarded by receiving the Jukai (Lay Ordination). Eventually, he was administrating and guiding a lay Buddhist meditation group from the same order. His interest in consciousness exploration, spirituality and religion led him to the study of the Hebrew bible. In his bestselling book “DMT – The Spirit Molecule: A Doctor’s Revolutionary Research Into the Biology of Near-Death and Mystical Experiences” he dives deeper into the intimate connection between spirituality, consciousness, spirituality and DMT. 

Photo by Marek Piwnicki, unsplash.com

Psychedelic Research inspired by Eastern religion

Inspired by his interest in Eastern religion, meditation practices and research expertise, he began his scientific endeavour with psychedelic substances and spirituality (more about his spiritual practices later). In an interview for “Medium”, he emphasised that it was the qualitative and descriptive overlap of psychedelic experiences and Eastern meditation practices that further nurtured his pursuit on attending a career in the field of psychedelic research. 

As mentioned before, Strassmans earlier work focuses on the role of the pineal gland and melatonin in the human and mammalian brain. Interestingly, the pineal gland is often considered the “seat of the soul” in many religious and spiritual communities, with its significance dating far back to the times of the early Egyptians. 

Eventually, based on evidence from Strassman and other researchers, it has been shown that the pineal gland can produce endogenous DMT, potentially accounting for profound experiences, such as birth and near-death experiences (Dean et al., 2019). Ultimately, the interplay of rigorous spiritual and religious exploration, combined with his earlier scientific work, Strassman’s curiosity paved a road that led him to become an important figure in early and current DMT research. 

After the “war on drugs” and the associated pause of psychedelic research, Dr. Strassman was involved in conducting the first government-approved human experiments of psychedelic substances in the ’90s, with a special focus on the safety and psychopharmacology of DMT. While his earlier publications were often dedicated to the fundamental mechanism, safety and pharmacology of the drugs in a healthy population, his more recent research specified in exploring the therapeutic potential of DMT in stroke rehabilitation. Within this realm, Dr Strassman was and is involved in the investigation of prolonged intravenous infusions of DMT. 

Prolonged DMT IV-Infusions

For the psychedelic-drug-educated reader, this sub-heading may come surprising, as serotonergic hallucinogenic drugs are usually accompanied by tolerance and cross-tolerance effects. However, as Rick Strassman describes in an interview with “Drug Discovery & Development”, in the early 90s his research team observed that one can repeatedly dose DMT without inducing tolerance. Being a researcher at heart, the psychiatrist sought and received funding from the NIH to investigate the tolerance effects of repeated DMT dosing in an experimental setting. In their research, they administered the psychedelic every 30 minutes four times and surprisingly did not note any tolerance effects. Consequently, the idea was planted that DMT may be induced as a prolonged intravenous infusion, rather than the more common method of smoking or intravenous bolus injections. 

According to Strassman, this may be an interesting, innovative psychotherapy model for exploring the psychological, pharmacological and therapeutic effects of DMT in humans. While it is difficult to stop a full-blown psychedelic experience after a moderate to large bolus injection (one-time dosing) of magic mushrooms or LSD, one can vary the IV infusion rate of DMT to alter the strength of the experience. Once the IV infusion is stopped, the psychedelic experience will be over after a few minutes. 

During his interview at Drug Discovery & Development, Dr Strassman shared insights into ongoing research at UCLA, where repeated dosing of DMT is being explored as a potential treatment for veterans with post-traumatic stress disorder (PTSD). This novel approach involves administering a substantial dose of DMT followed by periods of processing, allowing individuals to delve into their experiences over several hours. Continuous dosing, compared to one-time dosing offers clinicians the control to induce periods of rest and processing by reducing the infusion rate of the substance.

Additionally, results from the publication with Dr. Gallimore about the pharmacological effects of continuous dosing, this form of DMT administration may offer the opportunity to carefully characterize the subjective effects of the psychedelic compound. Furthermore, this protocol allows for a more controlled testing opportunity to use brain-imaging technologies to study the psychoneuropharmacological effects of the compound. 

Conclusion

In closing, Dr. Rick Strassman’s pioneering work in consciousness exploration and psychedelic research offers a glimpse into the potential of these substances for therapeutic purposes. From his early studies on the pineal gland to his current investigations into prolonged DMT infusion, his journey underscores the profound connections between science, spirituality, and healing. As we continue to delve deeper into the mysteries of the mind, Dr. Strassman’s insights serve as a guiding light, illuminating new pathways for understanding and growth.

Are you curious about this topic or want to ask Rick Strassman a few questions? Join our upcoming online event! 

By Simon Jost 

Brendan Borrell’s recently published New York Times article The Psychedelic Evangelist, about Johns Hopkins University’s late pioneering researcher Roland Griffiths, joins a series of blog posts, news articles and academic papers discussing problematic aspects of psychedelic science. Some of these concern personal misconduct, but others are rooted much deeper. Psychedelics bring together human psychology and chemical compounds, science, metaphysics and cultures. They are explored by pharmacologists and philosophers, anthropologists and psychiatrists, all trying to study what’s in a psychedelic, each with their own vocabulary and worldview. Some of the problems which arise from psychedelic research represent old schisms between the sciences and the humanities, and questions about knowledge as a whole. Here too, psychedelics seem to have a revealing effect, exposing our own thinking mechanisms.

Mystical science

The concept of “mystical experiences” has been one of these subjects of ongoing discussion. According to the Cartesian view, the spiritual and the experiential are in principle beyond the bounds of science, as they can neither be confirmed nor refuted. Thus uncomfortable feelings around their appearance in scientific articles can be easily understood. In The Language of Metaphysical Experience, Alan Watts relates to a similar problem encountered by physics in relation to unknown fundamental entities. While these cannot be explained and remain mysterious, they can be related to in quantitative terms for prediction purposes. For example, we can say that “dark matter makes up 30.1 percent of the matter-energy composition of the universe“ without knowing what ‘dark matter’ is. In the same way, we can put ‘mystical experiences’ on a scale, and measure how many subjects experienced them, their level of intensity and so forth. Even if such information enables prediction, ontologically such statements remain meaningless, or as Alan Watts puts it: “By admitting a few numbers, even ‘Jabberwocky’ may become scientific”.

‘Mystical’ is surely an eye-catcher, but psychedelic literature is abundant with what Bateson called “heuristic concepts”: concepts which bring to the table more fog than clarity. Consider for example ‘connectedness’, ‘awe’, ‘oneness’, ‘ego-death’, ‘oceanic boundlessness’, or even basic terms like ‘mind’ and ‘consciousness’. Do we really know what they mean? Humanities scholars thoroughly discuss and contextualize such terms, like the mystical in religion studies or awe in art and philosophy. As they travel to the hard sciences and find themselves in quantitative questionnaires, they can become inaccurate and biased.

These are differences within disciplines in our own culture; stepping outside reveals a deeper abyss, but it could also help in bridging gaps. In the same essay, Watts elaborates on differences between Western and Asian conceptualizations of metaphysics and their purposes. In the West we see metaphysical statements as conveying positive information about Reality. In Asia they are treated as remedies to frustrating human psychological ‘unreal’ problems, while Reality itself is ineffable. There is indeed something paradoxical about using objective terms and methods like observation to understand a subjective phenomenon like the psychedelic experience. There is a constant need to find less subjective terms: from ‘bad trip’ to ‘negative’, ‘adverse’, ‘challenging’ experience. The latter may sound more scientific than hippy, but aren’t they all personal value judgements of subjective experiences? Do they tell us anything objective at all? Another example is the quest to compile THE playlist for psychedelic interventions. Can there be one or even multiple recommended playlists? Is music not a matter of personal taste, memories and associations, of cultural references and education?

Experiencing objectivity

Some of the challenges are anchored in psychedelics’ legal status as schedule I drugs and the wish to develop them into treatments for medical conditions. Here too, our web of ontological assumptions and scientific methods keeps getting entangled, sometimes creating dangerous traps. Trying to stay as objective as possible, we wish to minimize the “human element” in order to properly assess the efficacy of substances. We use blinding and placebo-controlled trials, but this very practice sometimes leads to a nocebo effect (worsening of symptoms due to not getting the treatment) and even death, as described in the New York Times’s article. In many cases, practices applied to enhance objectivity are reinterpreted by participants as cold or unempathetic, and thus end up influencing results. For example, in order to minimize bias, the FDA recommends that a trial’s in-session monitor would not be involved in post-session psychotherapy. The assumption is that a therapist may be biased, in the sense that they know what happened during the psychedelic session and may use this information later. For participants, this means there is no continuity between the psychedelic session and the integration part (if there is one). This, in turn, creates trust issues and makes it difficult for participants to let go and to share their experiences. Since the therapy element is so determinate and hard to measure, psychotherapy and psychological support are often minimized in trials (also due to financial reasons), raising ethical concerns and undermining potential benefits. So some of the measures taken to accurately determine the safety and efficacy of psychedelics are in themselves a detriment to the safety and effectiveness of trials.

Medicalization as a goal has received much critique. Different approaches, as manifested by indigenous cultures or even by counterculture are often regarded as less or not at all valid. But even within mainstream culture, and within medicine and psychiatry, psychedelics raise some thoughts about the very definitions of mental illness, health and well-being. Here are a few: how come psychedelics seem to work for so many different mental disorders? Could it be that the terms “placebo” and “inner healing” refer to the same thing? If placebo works so well, why do we focus on external solutions which would prove better, instead of trying to enhance placebo? Some say that psychedelic research is leading to a full-blown paradigm shift in psychiatry, integrating social and cultural factors into conceptualizations of mental disorders and to transformation as the new basis for psychiatry.

Wired by culture

Known since the beginning of the 1960’s, ‘Set and Setting’ is the main mechanism through which subjectivity and culture enter the psychedelic experience. Indeed, many academic papers include an apologetic paragraph acknowledging the importance of these two illusive and immeasurable components, before embarking on a futile battle to neutralize them. 

Originally referring to a person’s mind-set and environment during a trip, set and setting bring into the psychedelic experience a complex web of one’s personal history, tendencies, mood, culture, environment and education. And all of these together influence participants’ interpretations, the meanings they give to their own experiences. In 1997, Betty Eisner added the Matrix component, one’s broader cultural frame. Then, in American Trip, Ido Hartogsohn expanded it to a Collective Set and Setting of a nation with its particular history and sociocultural context. Our Collective Set and Setting influences not only participants, but researchers and therapists as well. It can include, for example, the infamous hype of the psychedelic renaissance, articles we’ve read, films and documentaries we watched, stories and images from the 1960’s counterculture and echoes from the “War on drugs”. Back in 1959, Anthony F.C. Wallace already attributed the discrepancy seen between reactions to mescaline of Westerners and indigenous people to their cultural beliefs. While white subjects reported ‘going mad’ (e.g. mood swings, losing touch with reality, forsaking social inhibitors, etc.), such phenomena were not felt by the indigenous group, who remained generally stable and positive. Wallace concluded that the differences stemmed from the cultural conceptualization of hallucinations. In Western psychiatry, hallucinations are perceived as signs of mental illness, while in the indigenous culture, they are considered normal and even desirable.

Several elements in the setting of Griffiths’ lab were deemed problematic by Dr. Richards. It is easy to see how participants’ interpretations and experiences may be affected by a Buddha sculpture. But in fact, a ‘neutral’ setting does not exist. A hospital building carries its own associations, the outside and inside appearance of clinics also matters. According to Art literature, even white walls are not neutral. Music, smells… There is no way out; everything matters, from the size of the room and type of furniture through the number and gender of people present, to perceptions and beliefs of researchers, therapists and participants about psychedelics, people and the world. Moreover, not only do they affect trial results, but also their design, our research questions and our approach to the process. For example, a study aimed at minimizing nausea during consumption of Ayahuasca treats it as an undesired side effect, while another can regard it as an act of cleansing conducive to positive changes in well-being. Simply put, Set and Setting cannot be kept away from the lab.

Psychedelic research is full of contradictions, paradoxes and absurdities. We strive for total control and meticulous procedures to study substances which make one lose control and reflect on your own processes. We wish to eliminate anything weird or mysterious, but also dream of discovering a “magic pill”. As meanings, chemicals, cultures and personal tendencies collide, interdisciplinary research can supply the necessary means – perhaps not to overcome all contradictions – but at least to understand them better and to live with them as best as we can.

By Annabelle Abraham

Meet Bernardo Kastrup

Are you ready to flip the script of reality and dive deep into a world that is purely mental and not so much physical? Meet the founder of Essentia Foundation , PhD. Bernardo Kastrup.  Blending neuroscience and philosophy, his captivating ideas are embedded in the concept of analytical idealism. Brace yourself for a mind-bending journey beyond the confines of conventional thought. Join Bernado for his upcoming call at OPEN Foundation ! The next lines aim to give you a general understanding of his ideas about the reality of the mind and eventually bridge analytical idealism with psychedelic experiences.

Does our perception align with reality?

Let’s start by taking your eyes away from the screen and observing what you perceive in the world around you. The wall in your room, the trees in the park, the clouds in the sky or the sounds of the birds. Intuitively, we believe that what we perceive accurately reflects the world outside of us – a mirrored image of the external world in our consciousness.

If this were true – we would have a fully transparent window into the world outside – we would all drown in what the analytical idealist Bernardo Kastrup calls “an entropic soup”.  To understand that metaphor it is important to grasp the general concept of entropy.

What is Entropy?

Entropy is a fundamental concept in thermodynamics that is often described as the measure of randomness or disorder of a system. Imagine a brand new deck of cards that has never been shuffled. This represents low entropy because there is not a lot of randomness. Now think about shuffling this deck of cards. We created a high entropic state that is not very organized but rather chaotic. Let us keep this concept in mind when we dive deeper into the concept of analytical idealism.

“The entropic soup”:  the world looks nothing like what we perceive

From the perspective of “the entropic soup”, the world around us is highly entropic because it’s full of complexity, randomness, and disorder. Think about all the diverse and chaotic phenomena we encounter every day: from the unpredictable weather patterns to the bustling traffic on city streets, to the entangled interactions of living organisms in highly complex ecosystems. According to the second law of thermodynamics, if we perceive the world as it is, including the immense chaos and disorder, our brains would all drown in a hot, entropic soup. Consequently, through evolution, our brains learn to make sense of the world by using a simplified “user interface” or a “dashboard” that can help us navigate and make sense of a highly chaotic environment. Like a dashboard in a pilot’s cockpit that depicts the wind strength by representing it on a dial with an arrow (see picture below). The dial does not show the wind itself but is rather a representation of the wind. Bernardo states that “the world in itself looks nothing like what we perceive. We are merely using a virtual user interface to make sense of the chaos outside. More about that later. First, we will investigate mainstream ideas of consciousness and the world.

Pilot making sense of the world with the help of a dashboard.

Foto by William Topa, unsplash

The limitation of physicalism: The hard problem of consciousness

According to physicalism, all there is can be described in quantities. Physical relations and matter are the basis of everything. Therefore, the reality of the mind and the world itself – in the eyes of a physicalist  – can be fully explained by abstract quantitative mathematical relationships. Hence, the mind including all of its rich qualities, such as the experience of rain on your skin or the smell of freshly baked cookies, is caused by physical brain activity.   

However, Bernado Kastup does not agree with this view and states “There is something very wrong with this story that brain activity generates conscious experience.” Indeed, cognitive neuroscientists have still not solved the “hard problem of consciousness” (as defined by David Chalmers). The question remains how can a purely quantitative, physical entity give rise to complex qualitative experiences?

Bernardo suggests we imagine a scenario where a scientist has all the knowledge about the brain’s structure, its neurons, and how they interact. They know everything about brain activity when a person sees the colour red – the firing of neurons, the release of chemicals, and so on. However, no matter how much they understand about the brain’s physical processes, they still can’t explain why seeing the color red feels the way it does to the person experiencing it. This inability to explain subjective experience purely in terms of physical processes is what constitutes the hard problem of consciousness.

Perhaps it is necessary to shift our world paradigm to allow answers to this problem. One proposed solution may be Bernardo Kastrup’s analytical idealism.

What is analytical idealism?

Contrary to physicalism, in the philosophical perspective of idealism, reality is fundamentally mental or dependent on consciousness. In other words, the external world and its phenomena are products of mental constructs or perceptions. Similarly, analytical idealism is embedded in idealism and posits that the essence of the universe is an “intrinsic view”, suggesting that reality fundamentally resides in subjective experience. Analytical Idealism  is rooted in and driven by post-enlightenment principles such as conceptual parsimony, coherence, internal logical coherence, explanatory capability, and empirical sufficiency.

How does analytical idealism explain consciousness and reality?

While physicalism states that brain activity causes experience, analytical idealism argues that brain activity is just the depiction of experience. To understand Kastrup’s argument, one needs to take a few steps back and briefly review the basic assumptions that analytical idealism is based on.

Kastrup emphasizes that there are three empirical givens that we can be fully certain about:

 1) There is experience.

Before we start to theorize, all we have is experience.  

2) Brain function is a perceptual experience

For example, a neurologist who perceives the image created with a brain scanner.

3) The brain is made of what we colloquially call and perceive as “matter”.

Importantly, whatever we call matter, whatever it is, it underlies both the brain and the universe and thus creates space for a kinship between them. 

Building on these statements, analytical idealism states that brain function is what one’s inner conscious life looks like when it is observed by a neuroscientist through a brain scanner. Consequently, Bernardo Kastrup emphasizes that brain function does not generate a conscious inner life, because this leads to the “hard problem of consciousness”. Rather, he elaborates that conscious inner life is intrinsic; it is the essence that can be observed from an outside perspective with the help of a brain scanner. In other words, a brain scan is merely the representation of conscious inner life, but it is not consciousness itself.

The universal consciousness with multiple personalities

Bernardo Kastrup’s analytical idealism conceptualizes and builds upon one universal consciousness. To introduce this idea, the philosopher often uses the analogy of Dissociative Identity Disorder (DID). DID is a psychiatric condition that involves the presence of two or more distinct personality states (also known as “alters”) within the same individual. Using this analogy, he argues that we are dissociated alters of universal consciousness. Because of dissociation, we believe to be individual minds. With that being stated, all that lies beyond our dissociative boundary constitutes a broader “universal consciousness” and thus is mental by itself.

How do we make sense of the world according to analytical idealism?

One important concept in the theory of analytical idealism is “impingement”. Imagine you had a stressful fight with your housemate, partner or friend just before work. During work, you have to function, which is why your mind automatically compartmentalizes the stressful event and “parks it” to set it aside. According to Kastrup, this is a kind of “deliberate light dissociation. Your mind as a whole did not stop to feel the emotions, they are just more in the background, dissociated from your executive ego. However, you notice that you are easily irritable or disorganized during your work. The stressful event can still influence the ego despite the creation of a dissociative boundary. In other words, the mind outside of the boundary impinges across the dissociative boundary on the ego within.

What happens outside of our dissociative boundary are ideas and emotions that impinge on our mental dissociative boundary and result in us perceiving the world outside. Kastrup explains that the dissociative boundary “forms a screen on which outside mentation impinges, or is projected as perceptions”.

The dashboard in the pilot’s cockpit is the extrinsic appearance of the world outside as represented by dials measuring wind, temperature, etc. Similarly, the “perception is the extrinsic appearance, as represented in an alter`s dashboard of dials, of the ideas and emotions in universal consciousness”.

Model displaying how we are all dissociated alters with dissociative boundaries of a larger, shared universal consciousness.

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How do neural correlates of psychedelics substantiate the argument of analytical idealism?

Psychedelic experiences are often perceived as one of the most profound experiences of a user’s life. People often report that psychedelics induce a rich altered state of consciousness with enhanced senses and deep insights. Interestingly, the intense psychedelic experience does not correlate with increased brain activity, but neuroscientists show that rather the opposite holds! Psychedelics reduce overall brain activity. Especially, from the perspective of physicalism this is surprising. The argument of physicalism assumes that brain activation is the cause of subjective experience, so how is it possible that lower brain activity can give space for an enriched experience?

Psychedelics reduce dissociation and increase entropy

Kastrup explains that the reduced brain activity, induced by psychedelic substances, represents reduced dissociation. In other words, brain activity measured by brain scans is a picture of this dissociation process. Psychedelics reduce dissociation which correlates with a richer, more intense and profound experience due to the alleviation of dissociation itself. By reduction of dissociation, the dissociative boundary becomes more permeable, which allows the transpassing of elements from beyond the boundary to reach the alter within. We experience trance, the trespassing of mental elements across dissociative boundaries, while our brain activity is largely reduced.

Model displaying that psychedelics (here psilocybin-containing mushrooms) can make the dissociative boundary more permeable.

Perhaps, as Kastrup suggests, the increased connection to the world outside and other people, as perceived during a psychedelic experience may reflect the reduction of dissociation, which brings us closer to “universal consciousness” and the other alters by allowing the crossing of mental entities from beyond the boundary that surrounds our alter.

Bernardo argues that the end of life is the end of the dissociative process. By reducing dissociation we may get into a similar state like death. If psychedelics reduce dissociation, this should elicit an experience similar to death. Indeed, psychedelics can induce the experience of “ego death”  (dissolution of the sense of self) and have been found to share similarities with near-death experiences, which is consistent with Kastrups theory. This observation may further substantiate this theory.

Conclusion

In conclusion, Bernardo Kastrup’s analytical idealism presents a thought-provoking perspective on the nature of reality and consciousness. By challenging the traditional paradigms of physicalism (and others), Kastrup offers a framework where consciousness is not merely an emergent property of brain activity but is fundamental to the fabric of existence. Through concepts like dissociation and impingement, he elucidates how our perception of the world is shaped by our mental processes, bridging neuroscience with philosophy. Furthermore, Kastrup’s exploration of psychedelic experiences provides intriguing insights into the relationship between consciousness, brain function, and the dissolution of ego boundaries. Overall, Kastrup’s ideas invite us to reconsider our understanding of reality, consciousness, and the interconnectedness of the universe in a manner that transcends conventional thought.

Are you curious about this topic or want to ask Bernardo Kastrup a few questions? Join our upcoming online event that will go into depth about analytical idealism! 

By Simon Jost 

Introduction

What substances come to your mind if you think about sexual enhancement? Viagra? Alcohol? Amphetamines? Maybe over-the-counter natural products like Gingo Bilboa? 

Many psychonauts and plenty of anecdotes describe that altered states of consciousness – induced by psychedelics, such as psilocybin (the active component of magic mushroom), LSD, or  5-meo DMT – can foster an intimate, novel and magical sexual experience. But is there also evidence for positive effects on sexual functioning that outlast the drug experience and carry over into the sober, everyday life?

In the recent Nature publication, first author Tommaso Barba – who was recently a guest speaker at OPEN foundation – together with a research group from Imperial College London, suggest that psychedelics may enhance sexual functioning for up to 6 months after a trip! Tommaso believes that “this is the first scientific study to explore the effects of psychedelics on sexual functioning”.  Importantly, the researchers emphasize that their study does not cover “drug-sex” (sex during a trip), but rather captures the long-term effects of psychedelic experiences and psychedelic-assisted therapy that outlasts their pharmacological effect by far. In other words, the aim was to explore and understand differences in sexual functioning weeks and months after one experienced a psychedelic trip.

‘As I sit silent, away from you, you come into my mind. Caressing me gently with your limitless body. Stroking my heart with soft sand, holding my hand. Unwinding my mind, intertwining to the divine, into the forest we slip, deep, dark, unknown guided by light, you gently lead me to the unfolding lotus. Kissing me with blue petals of love. 

– EROWID experience report of an LSD user with her partner 

Who were the participants?

The research group combined responses of almost 300 participants derived from two different studies. The first study recruited participants who already planned to explore psychedelics (such as ayahuasca, 5 meo DMT, psilocybin or LSD) recreationally or in a ceremony. Via an online survey, 261 people answered questions before their psychedelic experience, then four weeks and six months after. 

The second study reflects answers from 59 participants who were part of a clinical depression trial led by Professor Robin Carhart-Harris and aimed to assess the differences in efficacy between the antidepressant drug escitalopram (an SSRI) and psilocybin (the active component in magic mushrooms).

What results are indicated by the study?

Results of the study demonstrate sexual improvements for up to 6 months after the study! Improvements cover various dimensions of sexual functioning, such as the pleasure of sex, sexual arousal, attraction to their partner, acceptance of their own physical appearance, interpersonal communication, and a sense of spirituality related to sex. Neither of the two studies noted a change in the perceived importance of sex.

While both psilocybin and escitalopram decreased depressive symptoms equally well, the present study demonstrates that, compared to the psilocybin group, the antidepressant escitalopram is not related to sexual improvements, but rather worsening. Furthermore, half of the patients in the escitalopram group reported sexual dysfunction, compared to only 13% in the psilocybin group. This is huge because it highlights an important difference between the two substances and can indicate further research directions and hint at novel therapeutic applications.

How do the researchers explain these long-lasting effects of psychedelics on sexual functioning?

The most commonly reported lasting positive effects of psychedelic experiences usually involve higher openness (how curious you are to explore new experiences), connectedness (with yourself and to others), and elevated mindfulness (how present and aware you are in and of the current moment).

openness

An open state of mind after psychedelics may explain why participants reported exploring new sexual experiences more often after experiencing a trip. This in turn has been shown to increase perceived sexual functioning. The authors write that it is beneficial to maintain “a mindful and open state of mind for attaining a satisfactory sexual performance”.

connectedness

There is no question that psychedelics can produce lasting perceptions of connectedness. Feeling more connected psychologically, emotionally or physically to yourself or others enhances interpersonal intimacy and fosters a sense of comfort that ultimately improves the sexual experience.

mindfulness

Experiencing the moment, tuning in to one’s senses and being aware of one’s surroundings are all positive outcomes of higher mindfulness. Not only meditation but also psychedelics can increase mindfulness for a long time after a trip. Researchers suggest that mindfulness is important for one’s sexual performance and the satisfaction of the sexual experience.

brain changes

Brain researchers and psychologists suggest that psychedelic-assisted therapy may help patients relieve certain mental barriers and overthinking patterns by lowering the activity of certain brain networks that are involved in excessive self-directed attention. This is especially useful for people who suffer from excessive overthinking and rumination – as observed in depression.

spirituality

You may wonder what spirituality has to do with sexual performance. Spirituality almost functions as a combination of all the abovementioned factors. Spiritual individuals – and psychedelic users – often experience the “transcendence of the ego”. This shift away from self-centeredness can reduce performance pressure and self-consciousness during sexual activity, allowing for a more natural and fulfilling experience. Additionally, spirituality often brings about greater mindfulness, a willingness to embrace new experiences, and an elevated sense of well-being.

Why are these findings so important?

As the first author Tommaso Barba explains “On the surface, this type of research may seem ‘quirky’, but the psychological aspects of sexual function – including how we think about our bodies, our attraction to our partners, and our ability to connect to people intimately – are all important to psychological wellbeing in sexually active adults”. The relevance of healthy sexual functioning goes way beyond the satisfaction, pleasure and arousal one experiences before, during and after sex. Couple therapists often stress the importance of both sexual performance and the perception of one’s sex life, underscoring their pivotal role in nurturing a healthy and fulfilling relationship. 

Often psychiatric disorders are accompanied by reoccurring issues with sexual functioning. For example, individuals with depression often report anhedonia (the loss of experiencing pleasure), lower self-esteem, and struggle to accept and be satisfied with their physical appearance. These psychological constructs are central to healthy sexual functioning – psychologically and physically. Some therapists even suggest that impaired sexual functioning may be a central risk factor for some individuals to develop a behavioural disorder, such as depression or anxiety.

Patients who are treated with antidepressants often complain about sexual dysfunction. The results from this study may help to identify sub-populations that may benefit more from a psychedelic intervention. For example, sexually active individuals who suffer from depression with comorbid sexual dysfunction (or vice versa!) may benefit more from a psychedelic-assisted intervention compared to antidepressants (SSRIs). 

What are some pitfalls of these findings?

While all of these results are very exciting and illuminate the variety of positive effects psychedelics may induce, it is extremely important to maintain a critical mindset. Therefore, the following lines will reflect some of the pitfalls of the study and explain why we need more research to confirm and apply these findings.  

Even though the study integrated two different study groups (naturalistic users and participants in a clinical trial), the participants’ demographic background primarily reflects white, well-educated and heterosexual people. Secondly, the measurement of sexual dysfunction relied on self-report, which means that the improvements are derived from subjective opinions. Adding to that, the study did not include the evaluation of the sexual functioning of the (sexual) partners – hence, solely relying on one side self-report.

Conclusion

In conclusion, the study sheds light on the potential long-lasting benefits of psychedelics on sexual functioning, extending beyond the immediate drug experience. Despite being preliminary and not free of limitations, the findings underscore the importance of exploring holistic approaches to mental health and well-being, acknowledging the interconnectedness of psychological, emotional, and physical aspects of human experience. Moreover, they raise intriguing possibilities for therapeutic interventions targeting sexual dysfunction, particularly in populations where conventional treatments may fall short. However, it’s crucial to recognize the limitations of the study, such as the narrow demographic focus and reliance on self-reported data, highlighting the need for further research with more diverse populations and rigorous methodologies. Overall, this research contributes valuable insights into the complex interplay between psychedelics, mental health, and sexual well-being, paving the way for future exploration and innovation in this ever-evolving field.

By Simon Jost