5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity

Abstract

5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness that is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions (e.g., Advaita Vedānta, Mahāyāna Buddhism, inter alia). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing research; however, empirical evidence indicates that its remarkable psychoactivity is partially mediated via agonism of the 5-HT1A/2A (serotonin) receptor subtypes. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. We propose that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool with the potential to significantly advance our understanding of the psychological and neuronal processes which underpin cognition and creativity (e.g., downregulation of the default mode network, increased global functional connectivity, neuroplasticity, σ1 receptor interactions, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of our conjecture. Specifically, we argue that 5-MeO-DMT has significant neuropsychopharmacological potential due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., ego death). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective, and potential scenarios of abuse are addressed, particularly in the context of neuroethics, cybernetic manipulation, and military research on torture.

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Notes

  1. 1.

    The cybernetician Heinz von Förster worked successfully in radar laboratories during the Nazi Germany era, and he later immigrated to the USA via the secret operation PAPERCLIP which brought more than 17,000 German Nazi scientists to the USA (Jacobsen 2014). We will return to this topic in a subsequent section.

  2. 2.

    The present epoch is also termed the sixth mass extinction or “Holocene extinction” (Barnosky et al. 2011; Ceballos and Ehrlich 2018; Ripple et al. 2017) due to the rapid anthropogenic biodiversity loss which is comparable to other exogenously caused mass extinctions in the history of the planet earth (Régnier et al. 2015; Worm et al. 2006). That is, we are currently witnessing the first mass extinction caused by the behavior of a species. For comparison, the last Cretaceous–Paleogene extinction event was with a high likelihood caused by the impact of a meteorite or comet.

  3. 3.

    Temporally discounted utility refers to the value of a delayed reward multiplied by the discount function F(D), where D signifies the delay. Specifically, the ratio F′(D)/F(D) constitutes the discount rate which signifies how rapidly the discount function decreases as a function of diachronic reward delay (Hwang et al. 2009). In the context of neuroeconomics, high discount rates have been associated with various forms of addiction, i.e., substance and behavioral addictions (Monterosso et al. 2012; Saville et al. 2010). The “impulsivity construct” (e.g., poor self-control) has also been associated with genetic predispositions (Anokhin et al. 2011).

  4. 4.

    According to Hofstede’s recently updated 6D model, “indulgence versus self-restraint” constitutes the newly added sixth cultural dimension and it would be interesting to examine if this is cross-cultural difference is reflected at the neuronal level (e.g., differences in prefrontal inhibitory control circuitry). “Restrain stands for a society that controls gratification of needs and regulates it by means of strict social norms” (Hofstede 2011, p. 15).

  5. 5.

    In fact, the neologism “Capitalocene” has been proposed as a more accurate descriptor (Altvater 2016). Human pressure on the Earth system is primarily caused by the wealthy OECD countries. Their “ecological footprint” (cf. Dietz et al. 2007) is proportionally much larger vis-à-vis the rest of the world, i.e., due to overconsumption (a sheer waste) of resources. Hence, equity significantly factors into the equation of “the great acceleration” (Steffen et al. 2015). It is important to emphasize that the problem has interdisciplinary ramifications which cannot be fragmented—a creative transdisciplinary solution is needed.

  6. 6.

    The terminology is adopted from sociology, in casu, power structure analysis (Domhoff 1975), where the topic of power concentration has been thoroughly studied (e.g., Froud et al. 2017; Harvey 2007; Hill and Kumar 2009), for instance, with regard to the “fractional reserve banking system” (Foster and Holleman 2014) which has been described as “economic parasitism.” Currently, financial disparity has reached an extreme climax and statistics indicate that an extremely small ultra-rich segment (> 1% of the total population) owns ≈ 50% of the world’s entire wealth (i.e., ≈ $140 trillion are owned by an infinitesimal small minority; but see the “Global Wealth Report” from 2018 published by the Credit Suisse Research Institute). According to Forbes, wealth concentration in the USA has spiked in recent years. For example, “three men own as much as the bottom half of Americans” and the “richest American in 2018 was worth 31 Times as much as in 1982.” A recent big-data study conducted at the ETH Zürich provided insightful results. Based on graph-theoretical network topology analysis, a “super-entity” consisting of a network of global corporate control was identified (Vitali et al. 2011). The researchers concluded that “transnational corporations form a giant bow-tie structure and that a large portion of control flows to a small tightly-knit core of financial institutions,” an empirical finding which is indicative of a “richer-get-richer” mechanism.

  7. 7.

    The term “radical” is etymologically derived from the Latin word “radix” meaning “root” (cf. the radical sign √ in mathematics). That is, a “radical solution” refers to a solution which targets the very roots of the problem, as opposed to peripheral symptomologies (in the case under consideration, the roots are primarily psychological).

  8. 8.

    See Laplace’s “Essai philosophique sur les probabilités” (1814, p. 4).

  9. 9.

    URL: https://thebulletin.org/2018-doomsday-clock-statement

  10. 10.

    The binomial taxonomical nomenclature (introduced by Carl Linnæus) is etymologically derived from the Latin “homō” meaning “human being” and “sapiēns” meaning “wise”—thus the “wise human.” By contrast, the neologism Homō consumens has been proposed (Fromm 1976) as a more accurate/realistic designation given the contemporary utilitarian production and consumption orientation of the species (Baudrillard 1998).

  11. 11.

    Realistic thinkers have argued that the chances of species survival are de facto minute (Fromm 1962). However, classical game-theoretical calculi are not applicable to this situation. Even if the chance of success is < 1%, humanity needs to mobilize all its resources to come up with a solution to the problem of self-destruction.

  12. 12.

    Source: New York Times—May 25, 1946, p. 13—“Atomic Education Urged by Einstein” URL: https://nyti.ms/2NpSc8L

  13. 13.

    The importance of top-down executive control for the functioning of society has already been discussed by Plato in his Res Publica (Politeia). Plato placed great emphasis on the relation between self-discipline (synonymous with self-control) and justice, at the level of the individual and likewise the city-state (póli), as demonstrated in the following Socratic dialog:

    Socrates: ‘It is not the same as courage and wisdom. Each of those was located in a particular part, and yet one of them made the whole city wise, and the other made it brave. Self-discipline does not operate in the same way. It extends literally throughout the entire city, over the whole scale, causing those who are weakest - in intelligence, if you like, or in strength, or again in numbers, wealth or anything like that — together with those who are strongest and those in between, to sing in unison. So we would be quite justified in saying that self-discipline is this agreement about which of them should rule — a natural harmony of worse and better, both in the city and in each individual.‘[...] ‘The title `brave`, I think, is one we give to any individual because of this part of him, when the spirited element in him, though surrounded by pleasures and pains, keeps intact the instructions given to it by reason about what is to be feared and what is not to be feared.’ Glaucon: ‘Rightly so,’ he said. Socrates: ‘And the title “wise” because of that small part which acted as an internal ruler and gave those instructions, having within it a corresponding knowledge of what was good both for each part and for the whole community of the three of them together.’ Glaucon: ‘Exactly.’ ‘What about “self-disciplined”? Isn’t that the result of the friendship and harmony of these three? The ruling element and the two elements which are ruled agree that what is rational should rule, and do not rebel against it.’ Glaucon: ‘Yes. That’s exactly what self-discipline is,’ he said, ‘both for a city and for an individual.’

  14. 14.

    In this context, another cognitive bias is of pertinence: the “omission bias.” In sensu lato, omission bias refers to the irrational human tendency to judge omissions that cause harm as less significant compared to actions that cause harm because actions are perceived as more salient and hence consequential than inactions (DeScioli et al. 2011).

  15. 15.

    The Quinan “Web of Beliefs” (Quine and Ullian 1978) provides an applicable semantic analogy to (Bayesian) neural network connectivity and the process of “belief updating” (i.e., modification of weights between neuronal nodes).

  16. 16.

    The computer analogy (Casey and Moran 1989) forms the conceptual metaphoric basis of much of contemporary thought (Lakoff and Johnson 1981). Norbert Wiener wrote the following on Zeitgeist in his cybernetics book with the telling title “The human use of human beings” (1950): “… the thought of every age is reflected in its technique. […] If the seventeenth and early eighteenth centuries are the age of clocks, and the later eighteenth and nineteenth centuries constitute the age of steam engines, the present time is the age of communication and control.” A similar argument could be articulate with respect to Cartesian and Freudian “hydraulic” theories.

  17. 17.

    It is curious to remark that the Ouroboros shares numerous topological similarities with the Möbius band (a paradoxical geometrical object which has been eponymously named after the German mathematician August Ferdinand Möbius who described it in 1885). Interestingly, archeological excavations demonstrate that the Möbius band has been depicted in artworks across numerous ancient cultures and epochs (Cartwright and González 2016). The mathematical symbol for the concept of infinity, the lemniscate, shares central defining features with the Möbius band. We submit that the symbolism of the Möbius band can be interpreted as a visual conceptual metaphor, a figure of thought (Lakoff 1986), for the psychophysical “Pauli-Jung conjecture” of dual-aspect monism (Atmanspacher 2012). In abstracto, the Ouroboros is thus a symbol for second-order cybernetics (von Förster 2003), i.e., the recursive relationship between the seer and the seen (psyche and physis).

  18. 18.

    Much later, Walter Frederking utilized mescaline and LSD-25 for psychotherapy in order to facilitate “deep relaxation and free ideation” via “drug-induced dream-like states” in order to “shorten the course of psychoanalysis” by facilitation of profound insights (Frederking 1955, p. 262). Frederking postulated that these psychoactive chemicals could be used to establish a “close connection between the subject and his dreams.”

  19. 19.

    The etymology of the term is derived from the Ancient Greek ψυχή (psukhḗ, “mind, soul, spirit”) + δῆλος (dêlos, “to manifest, to reveal”), i.e., “psychedelic substances” could be adequately translated as “mind manifesting” or “soul revealing” substances. Similarly decomposed, psychology is “the study of” the “mind, soul, and spirit”—even though most contemporary psychologists would reject this “deep” definition. Previously, psychedelics were also labeled as “psychotomimetics” because they were thought to produce symptoms similar to those of a psychosis. Interestingly, schizophrenia and other psychopathologies involving psychotic symptoms (e.g., bipolar disorder) have been linked to creativity (e.g., Claridge and Blakey 2009; Power et al. 2015), possibly due to a reduction of latent inhibition (cf. Burch et al. 2006), inter alia.

  20. 20.

    It is a plausible hypothesis that psychoactive tryptamines are involved in naturally occurring dream states. Given its central function in biochronological processes, the pineal gland is an important neuroanatomical ROI (cf. Barker et al. 2013). Also note the close structural similarity between melatonin (N-acetyl-5-methoxy-tryptamine) and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine). There are numerous hypotheses which link dream states to creativity (e.g., Bob and Louchakova 2015).

  21. 21.

    It has been shown that the emotional valence of dreams can be systematically influenced by extraneous (i.c., olfactory) stimuli. It has been experimentally demonstrated that a positive smelling stimulus (rose smell) induced positive dreams while a negative smelling stimulus (the smell of rotten egg) induced negative dreams (Schredl et al. 2009). Similar perceptual/phenomenological interactions may be predicted for the emotional valence of psychedelic states (such techniques might be utilized to foster conditions which are conducive to the unfoldment of creativity or for therapeutic purposes). Furthermore, in relation to dreams and creativity research, “disjunctive cognitions” are another dream-state phenomenon of significant interest. During the perception of “interobjects,” the dreamer experiences novel disjunctive phenomena such as objects and geometrical structures that do not occur in general waking consciousness. These objects are self-contradictory and paradoxical, viz., they are incongruent with the axiomatic Aristotelian “laws of thought,” i.c., the law of the excluded middle, the law of noncontradiction, and the law of identity. It has been argued that dream events oftentimes feel bizarre but that disjunctive cognitions usually do not. The following example illustrates the point: “I’m sitting in a dream beside a man I do not recognize, but I know in the dream is my father” (Boas 1994, p. 155). This example could be interpreted as an inversion of the “Capgras’ delusion” (Young 2008), an interpretation which is particularly interesting in view of the fact that Capgras’ syndrome has been associated with the alteration of time perception (Aziz and Warner 2005), a factor which is common to dreams and psychedelic states. Echoing early Freudian theorizing, it has been suggested with regard to the emerging interdisciplinary field of neuropsychoanalysis that by “careful examination of the experiences in dreams, we may gain insight into the workings of our mind/brains” (Blechner 2001).

  22. 22.

    Cf.: Glaser, Gilbert (1955). “Neuropharmacology—transactions of the first conference”. The Yale Journal of Biology and Medicine. 28(1), 78–79.

  23. 23.

    It should be emphasized that these chosen examples should not reinforce the superficial conception that creativity only “matters” if it produces material dividends and has no intrinsic value in itself (Fromm 1976).

  24. 24.

    In a recent randomized double-blind trial, ≈ 70% of participants rated their experimentally induced psychedelic experience as one of their top 5 spiritually significant lifetime events (Griffiths et al. 2016).

  25. 25.

    Osmond first used the term in the scientific literature in 1957 in an article published in the “Annals of the New York Academy of Sciences” entitled “A review of the clinical effects of psychotomimetic agents” (Osmond 1957).

  26. 26.

    Huxley was a repeated nominee for the Nobel Prize in literature and his genealogy is related to many high-grade British scientists (Berra et al. 2010). An interesting factoid (especially in the context of ego dissolution/ego death) is that Huxley wrote a note to his wife while on his deathbed asking her to inject him with 100 μg of LSD (IM). Huxley died while under the influence of the consciousness-expanding substance. Another interesting piece of information is that Huxley was allegedly intimately involved in the illegal CIA MK-ULTRA program (discussed subsequently) which entailed psychological experimentation with psychedelic substances on naïve and nonconsenting subjects (oftentimes with extremely harmful consequences).

  27. 27.

    A connatural conception can also be found in Plato’s “Allegory of the Cave.” Plato was very much concerned with eternal forms and most mathematicians can be regarded as implicit Platonists (Burnyeat 2000; Mueller 2005) even though they might not be explicitly aware of this philosophical heritage (cf. the importance of Δianoia in Plato’s “Theory of Forms”; Cooper 1966).

  28. 28.

    Eristische Dialektik: Die Kunst, Recht zu behalten (transl.: Eristic dialectic: the art of winning an argument)

  29. 29.

    There is a crucial distinction between hallucinations and illusions which has been concisely pointed out by Sir Francis Galton: “A convenient distinction is made between hallucinations and illusions. Hallucinations are defined as appearances wholly due to fancy; illusions, as fanciful perceptions of objects actually seen.” (Galton 1883, p. 132). In sum, illusions have an ontologically existent object as a reference while illusions appear seemingly ex nihilo. Hallucinations and illusion can occur in all modalities (e.g., visual, auditory, tactile, olfactory, etc.) and there appear to be interindividual differences. Future studies should address these idiosyncrasies which might help to identify correlated receptor polymorphism and associated genetic loci of such perceptual predispositions. From an empiricist stance, sensory input forms the foundation of creative ideation (and cognition in general). The classical “Aristotelian Peripatetic Axiom” is of pertinence in this respect. Hence, a deeper understanding of illusions and hallucinations seems to be important for a more detailed understanding of the processes which undergird creativity. This epistemological argument highlights the importance of sensory input in the context of reasoning and knowledge: Nihil est in intellectu quod non sit prius in sensu (transl.: nothing is in the intellect that was not first in the senses).

  30. 30.

    Interestingly, it has been experimentally demonstrated that the feeling of awe expands perception of time, enhances well-being, and makes “life feel more satisfying than it would otherwise” (Rudd et al. 2012).

  31. 31.

    The concept of nonduality constitutes the nucleus of the Indian philosophical system of “Advaita Vedānta” (Sanskrit: अद्वैत वेदान्त, literally, “not-two”) which is one of the most ancient spiritual paths to self-realization (cf. Maslow’s concept of self-actualization). Overcoming/dissolving the illusion of the ego or I-ness principle (Ahaṃkāra) plays a crucial role in this meditative spiritual tradition which fosters deep insights into the transcendental nature of the Self.

    The experience of ego dissolution is fundamentally ineffable. Hence, the profundity of ego dissolution will not be fully comprehended by those readers who have not experiences it first-hand. It relates to the problem of noncommunicable quale: One cannot appreciate the taste of sugar by listening to elaborate descriptions or by studying its molecular structure. One must taste it (cf. Nagel 1974). In philosophy of mind, this is known as the “knowledge argument” (Jackson 1986).

  32. 32.

    Psychedelic were not only of interest to academic scientists. After initial studies in German concentration camps (e.g., Auschwitz), the CIA developed its own undercover programs (e.g., Project MK-Ultra) in order to test psychedelics compounds on vulnerable and naïve (nonconsenting) populations, e.g., prisoners, homeless people, and mental patients. We will briefly discuss these illegal research programs in a subsequent section.

  33. 33.

    John Daniel Ehrlichman who was at this time Assistant to the President (for Domestic Affairs) stated in an interview in 1994 (published in “Harpers” in 2016): “The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I’m saying? We knew we could not make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did.”

  34. 34.

    This is changing while we are writing this article. For instance, subthreshold microdosing of psychedelics has become a topic of renewed interest in the context of creativity (Anderson et al. 2019). While we were in the process of revising this paper (after initial submission), a first pilot study on 5-MeO-DMT was conducted by researchers in the Netherlands (Uthaug et al. 2019). This study experimentally demonstrated the positive effects of 5-MeO-DMT on convergent creative thinking, inter alia.

  35. 35.

    In the UK, the recently ratified “Psychoactive substances act” which reached Royal Assent in January 2016 complicates the matter by creating societal, political, and fiscal impediments to scientific research into the neurobiology of psychedelics. For more information, see: http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted.

  36. 36.

    Supraphysiological describes a level of efficacy which is unseen in organisms which evolved according to the principles of natural evolution.

  37. 37.

    Even though the chemical structure of both compounds is very similar, their psychological effects are incommensurable.

  38. 38.

    Albert Hofmann (1906–2008) also discovered LSD in 1938, but he was unaware of its psychoactivity until 1943 when he conducted the first self-experiment. Hofmann, who later served as a member of the Nobel Prize Committee, stated on his 100th birthday: “It gave me an inner joy, an open mindedness, a gratefulness, open eyes and an internal sensitivity for the miracles of creation. [...] I think that in human evolution it has never been as necessary to have this substance LSD. It is just a tool to turn us into what we are supposed to be.”

  39. 39.

    Interestingly, in the present context, OTE has been correlated with the ability to recall dreams (Watson 2003).

  40. 40.

    For instance, the Pearson correlation coefficient for “global creativity” and OTE is r = 0.655 and for “creative achievement” r = 0.481. By contrast, “Math–science creativity” is not statistically significantly correlated with OTE (r = 0.059; ns; for further correlation between various facets of creativity and the Big Five factors, see Silvia et al. 2009). The salient correlation between OTE and creativity has been reported in many studies (a pertinent meta-analysis has been conducted by Feist 1998; a recent study reporting a strong relationship between OTE and creativity has been conducted by Puryear et al. 2017). Furthermore, a meta-analytical structural equation model of 25 independent studies showed that OTE is the strongest FFM predictor of creative self-beliefs (r = 0.467; Karwowski and Lebuda 2016).

  41. 41.

    The interposition of the “space–time interval” which divides the percipient from the percept is an idea adopted from Jiddu Krishnamurti mentioned in his book “Freedom from the Known” (Krishnamurti 1969), while the reference to Kantian apriorism is an annexure. The importance of space–time in duality is especially intriguing given the fact that the effects of psychedelics are associated with phenomenological aspatiality and atemporality.

  42. 42.

    Novelty or sensation seeking is a robust predictor of risk taking and drug use. This might lead to a feedback loop in which those who are open to new experiences are more likely to be exposed to new experiences (such as psilocybin or 5-MeO-DMT) which in turn reinforce their open-mindedness.

  43. 43.

    Using human cerebral organoids and in silico analysis, it has been demonstrated that 5-MeO-DMT has modulatory effects on proteins associated with the formation of dendritic spines and neurite outgrowth (Dakic et al. 2017) which may influence neuroplasticity and hence ideoplasticity. 5-MeO-DMT has been found to match the σ1 receptor. Because σ1R agonism regulates dendritic spine morphology and neurite outgrowth, it affects neuroplasticity which forms the neural substrate for unconstrained cognition.

  44. 44.

    Bertrand Russel discussed the links between mysticism, creative intuition/insight, and logic in great detail in his excellent essay “Mysticism and logic” (Russell 1981).

  45. 45.

    The rich-club coefficient Φ is a networks metric which quantifies the degree to which well-connected nodes (beyond a certain richness metric) also connect to each other. Hence, the rich-club coefficient can be regarded as a notation which quantifies associativity. Conceptually related research concluded that “associative abilities represent valid elementary cognitive abilities underlying creativity” (Benedek et al. 2012). We submit that this line of thought connects to the quasi-Newtonian principle of idea formation described by John Locke in his seminal book “An Essay Concerning Human Understanding” (1689), specifically the chapter entitled “On the Associations of Ideas.”

  46. 46.

    Furthermore, the authors argue convincingly that the notion that LSD (and other psychedelics) “expand” consciousness is quantitatively supported by their data. Specifically, they argue that the neurophysiological changes associated with psychedelic states contrast with states of diminished consciousness (e.g., deep sleep or general anesthesia). The obtained results are congruent with the idea that psychedelic and unconscious states can be conceptualized as polar opposites on a continuous spectrum of conscious states. Furthermore, the authors suggest that the level of consciousness is quantitatively determined by the level of neuronal entropy (in accord with the entropic brain hypothesis formulated by Carhart-Harris et al. 2014). It has been suggested that Aldous Huxley’s “reduction valve” hypothesis appears to be relevant in this context.

  47. 47.

    Recent evidence focusing on changes in the coupling of electrophysiological brain oscillations by means of transfer entropy suggests that serotonergic psychedelics temporarily change information transfer within neural hierarchies by decreasing frontal of top-down control, thereby releasing posterior bottom-up information transfer from inhibition (Francesc Alonso et al. 2015).

  48. 48.

    A potential explanatory mechanism might be found in the entropic brain hypothesis (Carhart-Harris et al. 2014; Lebedev et al. 2016). Pertinent experimental evidence comes from a recent magnetoencephalographic (MEG) study which showed that classical psychedelics increase signal diversity (Schartner et al. 2017), a quantitative finding which appears highly relevant in the context of contemporary creativity research.

  49. 49.

    Interestingly, ego dissolution was also statistically significantly correlated with enhanced well-being/life satisfaction (ρ = 0.392). For alcohol (ρ = − 0.112) and cocaine (ρ = − 0.083), this positive effect was absent. However, due to the quasi-experimental nature of this study, no solid inferential conclusions are possible. Systematic experimental research is needed to elucidate this important topic which has obvious societal relevance.

  50. 50.

    The snuff was administered in a ceremonial setting in which the ground seeds of the cojóbana tree (Anadenanthera peregrina) were inhaled via a Y-shaped pipe called Cohoba (Wright and Ortiz 1941).

  51. 51.

    From an evolutionary vantage point, it is intriguing to note that the pineal functions as a photoreceptive neuroendocrine organ in numerous vertebrates (Lamb 2013). Functional and morphological congruencies between photoreceptor cells on the pineal and the retina are indicative of a close evolutionary relationship (Mano and Fukada 2006). Phylogenetically, the “pineal eye” was a paired organ with a similar structure to the lateral eyes. This ontogenetic development and the associated genetic pathway that regulates its development and neurogenesis strongly suggest that “the pineal eye and the lateral eyes share a common genetic and embryologic basis” (Benoit et al. 2016) That is, a shared genetic and molecular mechanisms undergirds their similarities (Tosini 1997). However, the pineal-specific physiological functions remain largely elusive. Note that our knowledge of the photoreceptor system is in general very incomplete; for instance, only recently, a new opsin (labeled melanopsin) has been identified (Provencio et al. 2000). We suggest that 5-MeO-DMT might further our understanding of the molecular and neurobiological basis of visual perception (and imagination)—especially with relation to the shared properties of the pineal and the retina. It is furthermore interesting to note that the “visionary” properties of 5-MeO-DMT might not be “merely” metaphorical, but that metaphorical linguistic descriptions convey a biological meaning which is hitherto only poorly understood (e.g., the expression “inner vision” or “introspection” might describe an actual visual process which “focuses” on a domain which is hitherto not sufficiently recognized). According to simulation theories of cognition (Hesslow 2012), it may be hypothesized that the visual system is intrinsically involved in “DMT-vision” and specifically the function of the pineal is of interest against this adumbrated empirical and theoretical background (cf. Benoit et al. 2016). To put it more poetically, 5-MeO-DMT might shed “new inner light” on molecular and psychological processes associated with vision, visionary power, and imagination.

  52. 52.

    Interestingly, the 5-HT1A receptor appears to be more important for the stimulus effects of 5-MeO-DMT than the 5-HT2A receptor (Shen et al. 2010). This has been experimentally demonstrated by various tests of antagonism of stimulus control with the 5-HT1A antagonists pindolol (also a nonselective β-blocker) and the silent agonist WAY-100635 (Winter et al. 2000).

  53. 53.

    It is important to note that 5-HT agonism does not explain the effects of all psychedelics. For instance, the naturally occurring dissociative hallucinogen salvinorin A (the active principal in the mint plant Salvia divinorum which has been utilized by indigenous Mazatec shamans) is not an alkaloid but a terpenoid which agonizes the κ-opioid receptor, but is inactive at the 5-HT receptor (Roth et al. 2002). It is therefore called an atypical psychedelic. Hofmann and Wasson were the first Westerners to collect a specimen of this extraordinary plant in Oaxaca/Mexico in 1962 (Casselman et al. 2014).

  54. 54.

    The researchers did not measure neurotrophins such as NGF and BDNF. Various growth factor concentrations would be a factor of great interest (cf. Rossi et al. 2006). Further, we suggest that 5-Meo-DMT affects mitochondrial bioenergetics and that this stipulated mechanism is pertinent in the context of 5-MeO-DMT–induced neurogenesis and neurorestoration (cf. Martorana et al. 2018). To facilitate a deeper understanding of the underlying mechanisms, future studies should also examine the expression of associated genes such as BCL2 gene (cf. Kuhn et al. 2005). Research along this line might provide important insights into the anti-addictive mechanisms of 5-MeO-DMT which are currently mainly hypothetical (Barsuglia et al. 2018; cf. McClintick et al. 2013).

  55. 55.

    For example, toad effigies and iconography (with accentuated glands) are found in archeological excavation from ancient Mayan and Aztec cultures, e.g., artworks of “Tlaltecuhtli”—the earth or earth mother as a monstrous toad (Furst 1972).

  56. 56.

    See, for example, https://www.fractalimagination.com.

    Interestingly, under the influence of low doses of LSD, spiders spin webs of greater regularity (Witt 1951). Other researchers applied fractal theory to investigate “the correlation between the fractal structure of spider’s web and the fractal dynamics of its brain signal” (Namazi 2017). Mathematics and particularly its subordinate branch geometry have always been regarded as cognitive activities which enable access to transcendental/metaphysical realms (e.g., Pythagoras’s theorem, Plato’s transcendent forms) and there is a long-standing well-documented interrelation between geometry, mathematics, and mysticism (e.g., sacred geometry, Fibonacci numbers, etc.), as has been pointed out by eminent mathematicians who argue for the pivotal importance of mystical influences in the history of mathematics (e.g., Abraham 2015, 2017). For instance, it has been argued that there is a close relation between geometry, space–time, and consciousness (Beutel 2012), a perspective which can be found in many religions and ancient wisdom traditions, e.g. Yantra (Sanskrit: यन्त्र) and Mandala (मण्डल) in ancient Indian schools of thought (also found in Buddhism, inter alia). Moreover, geometry was pivotal for the progress of the exact sciences like cosmology and astronomy. For example, when the Lutheran astronomer Johannes Keppler’s published his “mysterium cosmographicum” at Tübingen in 1596, he based his theory on five Pythagorean polyhedra (Platonic solids) which he conjectured form the basis of the structure of the universe and thus realize God’s ideas through geometry (Voelkel 1999).

  57. 57.

    The long history of human usage of this naturally occurring compound in various cultures suggests that it does not convey a significant disadvantage in terms of evolutionary fitness i.e., mutation/natural selection (cf. Martin and Nichols 2018). Profit-oriented pharmaceutical companies, on the other hand, actively market patented synthetic designer drugs which do not have any evolutionary track record and might cause all kinds of unforeseen neurological, genetic, and epigenetic problems in the long run (cf. Kim et al. 2009), for instance, the widespread prescription of methylphenidate (e.g., Ritalin) in preschool children (Keane 2008), based on questionable DSM-5 nosology (Phillips et al. 2012a, 2012b, 2012c, 2012d). In contrast to patentable psychopharmacological agents, there is no revenue model for naturally occurring psychedelics in the merely profit-oriented capitalistic paradigm.

  58. 58.

    An animal neuroimaging study conducted by Riga et al. (2014) showed that 5-MeO-DMT decreased BOLD responses in the striate cortex (V1) and the medial prefrontal cortex (mPFC).

  59. 59.

    Quotation by Francis Crick (*1916, †2004; co-discoverer of the molecular double-helix structure of DNA) from his book “The Astonishing Hypothesis: The Scientific search for the Soul” (published in 1994)

  60. 60.

    It has been argued that the amount of L-tryptophan (a precursor of 5-HT and DMT) is only available in minute amounts in human serum, i.e., the reported concentration is ≈ 12.98 ± 0.37 μg/mL (Comai et al. 2010) and that the availability of biochemical basic material constitutes a limiting factor. However, if this data is generalizable across various populations remains an open question which warrants further exploration.

  61. 61.

    Interestingly, the adaptogenic properties of melatonin have recently been emphasized (Zakharov et al. 2019) and we submit that 5-MeO-DMT likewise has adaptogenic properties which support organismal homeostasis on various levels (cf. recent research on its anti-inflammatory and neurorestorative effects). The “adaptogen concept” is controversial in mainstream science, but there is exists a plethora of evidence in support of its validity—mainly from Chinese research (Chen et al. 2008). Western science is slowly integrating the concept (Panossian et al. 2012). 5-MeO-DMT is specifically interesting in this regard as creativity might be seen as a psychological aspect of adaptation and psychological and physiological homeostasis might be intimately interlinked.

  62. 62.

    Interestingly, a related idea can be found in Islam. The concept of Jihad al-Nafs can be translated as “an inner striving or struggle to overcome the ego/nafs”—i.e., the great inner struggle to heal the heart’s diseases (see Al-Khomeini 1940; Al-Arba’ūn Ḥadīthān, transl.: “Forty Hadith”).

  63. 63.

    A connatural concept can also be found in Plato’s “Allegory of the cave” (Res Publica, book 7, 514a–520a). Plato was very much concerned with eternal forms and most mathematicians can be regarded as Platonists (Burnyeat 2000; Mueller 2005) even though they might not be explicitly aware of this philosophical heritage (cf. the importance of Δianoia in Plato’s “Theory of Forms”; Cooper 1966; Tanner 1970). Interestingly, Plato’s allegory has recently been revived in the context of quantum dynamics and quantum computation, particularly with regard to the quantum Zeno effect (Misra and Sudarshan 1977; Peres 1980; Stapp 2001) and “projected” reality perceived through noncommutative “sequences of measurements” (but see Burgarth et al. 2014).

  64. 64.

    Note that this statement is not objectively verifiable in a detached manner. It can only be derived from the first-hand phenomenological experience (i.e., ego dissolution caused by meditation, introspection, psychedelics, spontaneous epiphany, etc.). Ego-less pure awareness plays a central role in many ancient philosophical schools of thought (Advaita Vedānta, Mahāyāna and Zen Buddhism, Taoism, Sufism, i.a.). It also relates to the Western literature on the Cartesian and Heisenbergian cut, where the former refers to the dichotomy between the material world (res extensa) and its nonmaterial counterpart (res cogitans), while the latter refers to the cut between an object and its environment which is crucial in the context of modern quantum physics (see Atmanspacher 1997).

  65. 65.

    Irenæus (c. AD 196) wrote the following in “Against Heresies” (§2.1.3): “Since they say that something exists outside the Pleroma, into which they think that Power wandering from above came down, they must choose one of two views. Either this “outside” will contain the Pleroma and the Pleroma will be contained—otherwise there will not be something “outside,” for if anything is outside the Pleroma the Pleroma will necessarily be within what they call outside the Pleroma, and the Pleroma, with the first God, will be contained by what is outside; or else the Pleroma and what is outside it will be immensely distant and separated from each other. But if they say this, there will be a ‘tertium quid’ with this immense separation between the Pleroma and what is outside it, and this ‘tertium quid’ will limit and contain the other two, and will be greater than both the Pleroma and what is outside it, since it contains both in its bosom.” (Grant 1996, p. 108, cap. “Divine transcendence”). Here, the term pleroma could be translated as “fullness” and it thus emphasizes holism and totality in contrast to reductionism and the separation of constituent parts, e.g., pleroma tes theotetos (transl.: “the whole completeness of the divine nature” (Colossians 2:9). The antonym of pleroma is hystêrema (incompletion). Interestingly, a diagrammatic representation of pleroma (after the gnostic Valentinus) which consists of nested triangles and pentagrams is very similar to the Sri Yantra in Hinduism which symbolizes nonduality. Valentinus held there exists a tripartite typology of human beings, (1) the material, (2) the psychical, (3) the spiritual, while only the latter would be able to receive gnosis (knowledge) of the ultimate.

  66. 66.

    Indeed, anecdotal reports indicate that it can cause glossolalia and xenolalia which are very interesting linguistic phenomena that have been investigated in the context of religion and altered states of consciousness (cf. Grady and Loewenthal 1997; Kavan 2004) and also from a neuroscientific perspective (Philipchalk and Mueller 2000). We therefore suggest that 5-MeO-DMT is of great interest to researchers in these fields.

  67. 67.

    It has been argued elsewhere that “increased creativity may […] constitute a manifestation of posttraumatic growth, defined as retrospective perceptions of positive psychological changes that take place following experiences of highly challenging life circumstances” (Forgeard 2013, p. 245).

  68. 68.

    Interestingly, preliminary evidence suggests that psilocybin is effective in the treatment of addiction, depression, and obsessive-compulsive disorders (Bogenschutz et al. 2015; Carhart-Harris et al. 2016). This is congruent with the formulated idea that 5-MeO-DMT has the potential to change persistent habitual modes of thought.

  69. 69.

    This idea could be empirically tested, for instance, by utilizing a semantic priming paradigm in order to investigate spread of activation (as proxy for verbal creativity). Exemplary studies have been conducted with the dopamine precursor L-Dopa by, for example, Kischka et al. (1996) in order to investigate the role of dopaminergic neurotransmission in verbal creativity. Anecdotal evidence suggests that serotonergic psychedelics can enhance verbal creativity significantly (longitudinally). In the acute phase, many psychedelics interfere strongly with the linguistic system (a breakdown of semantic and syntactic facilities is oftentimes reported). Ergo, frontal and temporal lobe language areas such as Broca’s and Wernicke’s area and the arcuate fasciculus are likely involved. We suggest that temporarily induced receptive and expressive aphasia are of interest in this context. Further, the differential influence on the left and right hemisphere is a topic of great interest. It would be interesting to examine if 5-MeO-DMT releases the right hemisphere from contralateral inhibition, that is, does it influence hemispheric dominance (i.e., local vs. global processing in the context of asymmetric hemispheric lateralization of function); cf. “right hemispheric dominance theory of creative thinking” (Shen et al. 2013).

  70. 70.

    It should be noted that psychedelics might cause serious psychological harm to certain populations with psychopathological dispositions (possibly due to specific 5-HT receptor polymorphisms). In rare cases, the DSM-5 diagnosis “hallucinogen persisting perception disorder” (HPPD) is applied (low incidence rate) (for a review, consult Halpern et al. 2016). Careful psychological screening is crucial for ethically responsible research (for research safety guidelines, see Johnson et al. 2008).

  71. 71.

    A categorical syllogism (Greek: συλλογισμός, syllogismos, conclusion or inference) consists of three parts: the major premise, the minor premise and the conclusion, for example:

    Major premise: All men are mortal.

    Minor premise: Socrates in a man.

    Conclusion: Ergo, Socrates is mortal.

    Or in Aristotle’s terms: “Whenever three terms are so related to one another that the last is contained in the middle as in a whole, and the middle is either contained in, or excluded from, the first as in or from a whole, the extremes must be related by a perfect syllogism. I call that term middle which is itself contained in another and contains another in itself: in position also this comes in the middle. By extremes I mean both that term which is itself contained in another and that in which another is contained. If A is predicated of all B, and B of all C, A must be predicated of all C: we have already explained what we mean by ‘predicated of all’. Similarly also, if A is predicated of no B, and B of all C, it is necessary that no C will be A.” (Aristotle, Organon Analytica Prioria, Book 1, §4). Based on an extensive psychological analysis of the foundational question “Where does mathematics come from” (Lakoff and Núñez 2000), it has been argued that syllogistic reasoning is based on the logic of containment, i.e., it makes use of mental manipulations of container schemata which form the basis of inferential logic. From an embodied cognition/conceptual metaphor perspective, humans mentally represent (Boolean/set-theoretical) inferential laws in a quasi-Venn diagrammatic manner (Venn 1880) by utilizing specific spatiorelational image schemata (cognitive container schemata). Container schemata serve as mental representations of classical logical laws (e.g., principium tertii exclusi, modus ponens, modus tollens, etc.). Recent neuroimaging data support this “line of thought.” For instance, an event-related fMRI study (Goel and Dolan 2001) reported the involvement of the parietal visuospatial system in abstract three-term syllogistic reasoning (occipital–parietal–frontal network). Investigations of the neuroanatomical correlates of syllogistic reasoning thus corroborate the notion that syllogistic reasoning recruits neuronal circuitry associated with the computation of spatial relations (see also Goel et al. 1998) as already implicitly psycholinguistically implied by Aristotle’s formulation.

  72. 72.

    The absence of the middle term in both premises leads to a syllogistic fallacy, i.e., the fallacy of the undistributed middle (viz., non distributio medii).

  73. 73.

    From a philological vantage point, the term “deduction” is etymologically derived from the Latin deducere “to lead, to derive.” Thus, the premises lead (automatically) to the conclusion, i.e., the conclusion is logically derived. This formalization constitutes the basis of the deductive-nomological model (Popper–Hempel model) of scientific explanation.

  74. 74.

    The concept of interconnectedness is of utmost importance from an ecopsychology point of view (cf. Key and Kerr 2011). The formulated hypothesis thus has significant real-world societal significance. The illusion of disconnection from nature (Fromm 1962) lies at the root of many destructive human behaviors which have far-reaching detrimental consequences (individual and society, micro and macro are not separable—therefore individual changes translate into global changes). Impetus for the hypothesis at hand is partially derived from recent studies which indicate that classical psychedelics increase nature-relatedness (Forstmann and Sagioglou 2017; Lyons and Carhart-Harris et al. 2018).

  75. 75.

    The English language lacks terminology to describe many nonordinary states of consciousness (cf. Sapir-Whorf hypothesis of linguistic relativism). Sanskrit, on the other hand, is linguistically very rich in this respect. The word Nirvikalpa is a composite lexeme composed of the negatory/contra-existential prefix ni (not, without) and the term vikalpa (thought, conception), and it can be translated as “without conception, free from conceptual thought.” In the ancient but timeless Yoga Sūtras of Patañjali, it refers to the highest form of samadhi, i.e., mediation without thought and object, a nondual state of absorption without self-consciousness in which there is no distinction between knower and known (epistemology and ontology, the seer and the seen; cf. Dṛg-Dṛśya-Viveka).

  76. 76.

    We are nescient about intraocular administration of purified 5-MeO-DMT. However, given its relation to the pineal (which contains photoreceptors), this is a topic of empirical interest (the pineal has been referred to as the parietal “reptilian third eye” (Eakin and Westfall 1959).

  77. 77.

    The toad venom itself contains numerous bufotoxins which interact with the functioning of the cardiovascular system, e.g., the bufadienolide derivative bufagin—C24H34O5 (Jensen 1932).

  78. 78.

    We hypothesize that 5-MeO-DMT increases functional connectivity (a reorganization of the rich-club architecture) and that this modulation of neuronal connectivity is associated with enhancement of creativity. In brevi, as neuronal activity patterns change and neuronal circuitry is reorganized, new connections between concepts and ideas evolve. We argue that John Locke’s classical quasi-Newtonian theory “On the Association of Ideas” is relevant in this regard. Connectome-based predictive (CPR) modeling could be employed to evaluate this hypothesis quantitively. CPR is a relatively new statistical method which uses (linear) models to predict cognition (or behavior) based on whole-brain dynamics (i.c., functional connectivity patterns are used as predictors for specific outcomes) (Shen et al. 2017). Relating to the proposed hypothesis, the predictor would be functional connectivity (e.g., rich-club coefficient Φ) and the outcome criterion creativity (e.g., associative thinking). Whole-brain global functional connectivity maps could be utilized for the purpose of visualization, and local density variations could be contrasted post hoc (e.g., intrinsic connectivity contrasts).

  79. 79.

    Aristotle stated: “But as all influences require to be counterbalanced, so that they may be reduced to moderation and brought to the mean [...] nature has contrived the brain as a counterpoise to the region of the heart with its contained heat, and has given it to animals to moderate the latter, combining in it the properties of earth and water.” (quotation adapted from “The Complete Works of Aristotle,” Revised Oxford Translation, ed., J. Barnes, Princeton: Princeton University Press, 1984).

  80. 80.

    The obvious question is: Should science ever be dogmatic? According to current research, “intellectual humility” and “dogmatism” are antithetical polar constructs (e.g., Leary et al. 2017), with the former being conjugate with intellectual traits such as openness, curiosity, tolerance, and the ability to handle ambiguity.

  81. 81.

    From the poem “Auguries of Innocence” from William Blake’s notebooks named “The Pickering Manuscript” (1803)

  82. 82.

    “Kritik der reinen Vernunft” (transl.: Critique of Pure Reason) published in 1781

  83. 83.

    https://www.legislation.gov.uk/ukpga/2016/2/contents/enacted

  84. 84.

    Alcohol, which is legal and indeed systematically promoted by the alcohol industry (even in academia), has a very unsafe LD50 profile and is proven to be neurotoxic (Da Lee et al. 2005; Jacobus and Tapert 2013). Recent longitudinal research has shown that even moderate alcohol consumption has detrimental effects on various neuroanatomical structures (e.g., hippocampal atrophy). Psilocybin, on the other hand, has been shown to induce neurogenesis in the hippocampus in animal studies (Catlow et al. 2013).

  85. 85.

    URL: http://www.efsa.europa.eu/en/topics/topic/margin-exposure

  86. 86.

    Freedom of thought is crucial for democracy as it forms the very basis (s.c., a condicio sine qua non) for the right to freedom of speech/expression. As Erich Fromm articulated in his book entitled “The fear of freedom”: The right to express our thought, however, means something only if we are able to have our own thoughts; freedom from external authority is a lasting gain only if the inner psychological conditions are such that we are able to establish our own individuality (Fromm 1942, pp. 207–208). It can be juridically argued that freedom of thought (mental self-determination) is a cardinal principle in international law (jus cogens).

  87. 87.

    In an age in which public opinions are systematically manipulated (Bernays 1928; L’Etang 1999) and “consent is manufactured” (Chomsky 1992; Fleming and Oswick 2014), cognitive diversity is regarded as a disruptive factor which might interfere with the smooth workings of the “mega-machine” (cf. Fromm 1962; Mumford 1967).

  88. 88.

    In a symposium in 1958 Hebb stated that: “The work that we have done at McGill University began, actually, with the problem of brainwashing. We were not permitted to say so in the first publishing …”.

  89. 89.

    URL: https://nsarchive2.gwu.edu//nsa/archive/news/dodmans.htm

  90. 90.

    URL: https://www.darpa.mil

  91. 91.

    Its neuroscience-related agenda can be found under the following URL: https://www.iarpa.gov/index.php/research-programs/neuroscience-programs-at-iarpa.

  92. 92.

    URL: https://www.dni.gov/index.php/newsroom/press-releases/press-releases-2017

  93. 93.

    Operation NORTHWOODS is a paradigmatic historical example which illustrates the dark side of creativity (Cropley et al. 2010). The pseudonym refers to a plan which was formulated in 1962 (by the US Department of Defense and the CIA) to commit acts of terrorism against American civilians (false-flag attacks) in order to justify a war against Cuba (Bamford 2001). The proposal included highly creative and deceptive strategies such as hijacking planes and orchestrated violent terrorism in U.S. cities such as Miami and Washington (inter alia). Moreover, the malignant (psychopathic) proposal included the blowing up a U.S. ship, the attacking of a U.S. civil airliner (alleged passengers were a group of college students off on a holiday), the spreading of rumors in Cuba via clandestine radio, and even the manufacturing of evidence to blame the Cuban government for the accidental death of the astronaut John Glenn. The plan was approved by the Pentagon but rejected by President Kennedy. This geostrategic example demonstrates that the importance of creativity in U.S. military expansionism and it shows the importance of game-theoretical creative thinking. The world is seen as a “grand chessboard” (Brzezinski 1997) and creative moves and deception are essential “to win the war game.” The book entitled “PsyWar on Cuba” provides detailed background information on the case, and obvious parallels to the 9/11 “terrorist attacks” have been drawn (Elliston 1999). The original NORTHWOODS document (which was declassified in 2001) is accessible under the following URL: https://nsarchive2.gwu.edu/news/20010430/northwoods.pdf.

  94. 94.

    Given that the brain uses “electrochemical” signal transduction, there are two pathways to interfere with its functions: (1) the chemical route and (2) the electromagnetic route. Of course, both are of interest to the military and associated intelligence agencies. The former is discussed here to some extent, while the latter is omitted. We refer the interested reader to the highly controversial and influential work of José Delgado on the electrical manipulation of the brain (e.g., Delgado 1964; Delgado and Hamlin 1956) which has later been used for the purpose of “behavior modification” in humans, e.g., direct electrical stimulation of the amygdala via brain implants—intracerebral radio stimulation (cf. Delgado, J.M.R. (1969). Physical Control of the Mind: Towards a Psychocivilized Society. Harper and Row). Related contemporary neurotechnological successor systems are, for example, implantable brain–machine interfaces such as Neuralink™, a chronically implanted cortical neuroprosthetic device (cf. Wang et al. 2013) which is currently widely popularized by Elon Musk et alii (see Anjana 2019). In theory, the cortical implant provides (hackable) read and write access (770/777) to the brain. Musk outspokenly expressed the transhumanist long-term goal to achieve “symbiosis with artificial intelligence.”

  95. 95.

    Further information on the utilization of mescaline in Dachau can be found in the referenced report: U.S. Naval Technical Mission in Europe, Technical report no. 331–45: “German aviation medical research at the Dachau concentration camp” (1945).

  96. 96.

    Such pharmacologically assisted techniques facilitate “coercive interrogation without causing physical assault.” In the context of contemporary praxis, it has been pointed out that “shockingly, a great majority of countries despite the implementation of laws against the torture and being signatories to various international treaties are using torture (physical and mental) to ferret out truth from an unwilling person” and further that “hypno-sedatives and psychotropic drugs are presently being used to create a ‘twilight zone’ or ‘trance state’ to break down the psychological defenses of enemy spies” (Kapoor et al. 2008).

  97. 97.

    More humanistically oriented researchers worked on the psychotherapeutic effects of mescaline using “deep relaxation and free ideation” via “drug-induced dream-like states” in order to “shorten the course of psychoanalysis” by facilitation of profound insights (Frederking 1955, p. 262). During the therapy, the patient is confronted with his “essential problems” while the substance is psychologically active and further a “close connection between the subject and his dreams” is established.

  98. 98.

    To “sing” like a bluebird

  99. 99.

    Several CIA subprograms systematically investigated extrasensory perception and telepathy (Jacobsen 2017). Note in this regard that the harmala alkaloid “harmine” (which is found in the psychedelic phytochemical concoction Ayahuasca) was previously termed “telepathine” (Chen and Chen 1939). Harmine is a β-carboline which functions as a MAO blocker to enable the oral activity of DMT (i.e., it is present in the vine Banisteriopsis caapi).

  100. 100.

    The recruitment of Plötner by the CIA is reported in the book “Mescaline: A Global History of the First Psychedelic” (Jay 2019). A very different story is disseminated on Wikipedia (*.de and *.com) according to which Plötner lived in Schleswig-Holstein into the early 1950s under the alias “Kurt Schmidt.”

    In recognition of his “scientific merits,” Plötner became in 1954 a professor at the Albert-Ludwigs-Universität Freiburg. The university stated in 1961 in a letter to the Ministry of Education (Baden-Württemberg) that Plötner did not violate any ethical norms and that that his behavior was immaculate—expressis verbis: “daß Herr Dr. Plötner in keiner Weise gegen menschliche und ärztliche Ethik verstoßen, ja sich menschlich und ärztlich trotz der gegebenen schwierigen Umstände ohne Tadel verhalten hat.” It is now evident that Plötner lied during the investigations. For example, he conducted human experiments with aggressively toxic chemical chlorine trifluoride and asserted later that the compound would be completely harmless. See also: https://link.springer.com/content/pdf/bbm%3A978-0-230-50605-3%2F1.pdf.

  101. 101.

    https://www.cia.gov/library/center-for-the-study-of-intelligence/csi-publications/csi-studies/studies/vol-58-no-3/operation-paperclip-the-secret-intelligence-program-to-bring-nazi-scientists-to-america.html

  102. 102.

    It is noteworthy that the USA is by a large margin the absolute world leader in military spending—there is serious competition (but a lot of propaganda to justify military spendings). The estimate for 2018 was ≈ $649 billion for the USA, ≈ $61.4 for Russia, while the world total was ≈ 1822 (Stockholm International Peace Research Institute database, SIPRI). This expenditure is reflective of the explicit goal of “full-spectrum dominance” (Joint Vision 2020, U.S. Department of “Defense”). According to Wikipedia, “full spectrum dominance includes the physical battlespace; air, surface and sub-surface as well as the electromagnetic spectrum and information space. Control implies that freedom of opposition force assets to exploit the battlespace is wholly constrained” (see also Armbrust and Chomsky 2005). The Nobel lecture by Harold Pinter addresses this topic. URL: https://www.nobelprize.org/prizes/literature/2005/pinter/25621-harold-pinter-nobel-lecture-2005/. Based on this ubiquitous doctrine (i.e., a ruthless domination philosophy), it follows that the domination of the “psychedelic space” is likewise of military/hegemonic interest, specifically in reference to psychocybernetic control. We submit that this topic is of utmost psychological relevance in the current political climate which places great emphasis on indoctrination and mind control.

  103. 103.

    Source document: https://www.cia.gov/library/readingroom/docs/CIA-RDP99-00498R000100120112-7.pdf

  104. 104.

    Source document: https://archive.org/details/DOC_0000190090

  105. 105.

    Official reports on illegal intelligence gathering activities by U.S. federal agencies can be accessed under the following URL: http://www.intelligence.senate.gov/churchcommittee.html.

  106. 106.

    Full datasets (largely restricted access) and additional information on the study are available under the following URL: https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/NKTIZD.

  107. 107.

    The following pertinent statements have been ascribed to John Edgar Hoover who was the first Director of the Federal Bureau of Investigation (but see Gentry 1991): “When morals decline and good men do nothing, evil flourishes. A society unwilling to learn from past is doomed. We must never forget our history.” Furthermore, Hoover made the following epistemic statement which is reminiscent of Festinger’s cognitive dissonance theory (Festinger 1957) and Lerner’s associated just-world belief hypothesis (Lerner 1997): “The individual comes face-to-face with a conspiracy so monstrous he cannot believe it exists. The American mind has not come to a realization of the evil which has been introduced into our midst. It rejects even the assumption that human creatures could espouse a philosophy which must ultimately destroy all that is good and decent.” On a different occasion, Hoover reformulated this statement concerning “doxastic logic” : “The individual is handicapped by coming face to face with a conspiracy so monstrous he cannot believe it exists.”

  108. 108.

    For a morally engaging example which documents the “enjoyment” of psychopathic torture by CIA personnel, see the following pictorial URL: https://en.wikipedia.org/wiki/Abu_Ghraib_torture_and_prisoner_abuse#/media/File:Sabrina-Harman.jpg. We provide this “emotionally disturbing” information not as hyperrealist “war porn” (Baudrillard and Lotringer 2005) but in order to raise awareness to the inhuman activities of the military—an understanding which is crucial in order to appreciate the discussion at hand in a realistic context. This is particularly necessary because the military–industrial–entertainment complex (e.g., countless Hollywood movies, the “gaming” industry, etc.) generally depicts the military as an honorable and virtuous organization which “fights” for justice, freedom, and humanitarian values. The military–industrial–entertainment complex thus creates implicit associations (cf. Schreger and Kimble 2017) in the public mind (via hyperreal media in the sense of Baudrillard) and scientists are not immune to these unconscious associative imprints which often take place at a very early neuroplastic stage in Piagetian/Kohlbergian cognitive/moral development. It is therefore necessary to actively counteract these repetitive quasi-Hebbian strategies via reality-based emotional priming. However, it can be argued that humanity has already been thoroughly de5sensitized toward moral transgressions (and the suffering of others) due to constant habituation and associated adaptive homeostatic receptor–downregulation processes, i.c., emotion-dependent amygdala habituation (for an fMRI-data based discussion of the phenomenon, see Plichta et al. 2014). Such learning processes very likely have (quasi-Lamarckian) epigenetic effects which thus affect the molecular biology (e.g., methylation/gene expression) of subsequent generations of human beings (Dias and Ressler 2014), viz., besides direct environmental effects via Pavlovian/Skinnerian conditioning and Bandura-type model learning/social learning).

  109. 109.

    See letter by the former APA President Alan E. Kazdin to George Bush: https://www.apa.org/news/press/releases/2008/10/bush-interrogations.aspx

  110. 110.

    Source URL: https://harpers.org/blog/2010/05/apas-unpredictable-past/

  111. 111.

    The web never forgets and the statement has been mirrored by the Internet Archive under the following URL: https://web.archive.org/web/20030802090354/http:/www.apa.org/ppo/issues/deceptscenarios.html.

  112. 112.

    Adapted from the “Association for the Prevention of Torture” (APT). URL: https://www.apt.ch/content/files_res/tickingbombscenario.pdf

  113. 113.

    There are rather complex epistemological reasons for this position which we omit in the interest of parsimony (e.g., based on Sôritês paradoxon, deductive logic, and the quasi-Popperian problem of demarcation, i.e., at what point does a problem become a problem of “national security”).

  114. 114.

    In fact, ahimsā is not merely nonviolence but it is a principle of nonharming. It is a principle with far-reaching moral implications (but see Marques 2012) which also applies to animals and it is consequently of pertinence for experimentation on animals in science (see also Singer 1990).

  115. 115.

    Immanuel Kant, Gesammelte Schriften. Hrsg.: Bd. 1–22 Preußische Akademie der Wissenschaften, Bd. 23 Deutsche Akademie der Wissenschaften zu Berlin, ab Bd. 24 Akademie der Wissenschaften zu Göttingen, Berlin 1900ff., AA IV, 421 / GMS, BA 52.

  116. 116.

    We suggest that “somatic disidentification” (i.e., the insight that “I am not the body”) is a crucial therapeutic psychological mechanism with respect to the treatment of various traumata with 5-MeO-DMT (e.g., sexual abuse, physical abuse, but also body dysmorphic disorders such as anorexia nervosa which are based on a strong identification with the physical aspect of human existence). In another term, 5-MeO-DMT helps to transcendent the body/ego identity and enables a higher “spiritual” identification which allows for emotional detachment from traumata. This line of reasoning is based on the premise that the transcendental experiences occasioned by 5-MeO-DMT facilitate a remodeling/recasting of the self-concept (i.e., how the self is conceived).

  117. 117.

    The “Body of Principles for the Protection of All Persons under Any Form of Detention or Imprisonment” adopted by the UN General Assembly in 1988 prohibits “methods of interrogation which impair the capacity of decision of judgment.” (A/RES/43/173).

  118. 118.

    For instance, C.G. Jung wrote extensively about the “collective unconscious” and we should be very cautious with any powerful interventions into this domain of existence, especially when we are dealing with severely (dissociative) traumatic procedures in a military context. Neuroscience has only very recently begun to integrate the far-reaching implications which can be derived from the rich history of analytical psychology (for a historical discussion of various conceptualizations of unconscious processes in connection with contemporary neuropsychological findings, see Bob 2003).

  119. 119.

    Expressis verbis from the official statement of the Bulletin of Atomic Scientists. URL: https://thebulletin.org/2018-doomsday-clock-statement

  120. 120.

    The fallacy of the undistributed middle (non distributio medii): Major premise: To improve things, things must change. Minor premise: We are changing things. Conclusion: Therefore, we are improving things. N.B. Often the proposed solution is depicted as “the only alternative.”

  121. 121.

    For example, Chomsky, N (2003). The functions of schools: Subtler and cruder methods of control. In D. A. Saltman & D. Gabbard (Eds.), Education as enforcement: the militarization and corporatization of schools. New York: NY: Routledge, pp. 25–36.

  122. 122.

    The essential Humboldtian ideals of independent academic institutions (which safeguard academic freedom) have been replaced by the military–industrial–academic complex and a profit-oriented business model (Chomsky 2015); see also the effects of intrinsic versus extrinsic motivation on creativity (Prabhu et al. 2008).

  123. 123.

    The triad has been addressed in the book entitled “University in Chains: Confronting the Military-Industrial-Academic Complex” (Giroux 2015). Military Keynesianism refers to the stance that governments should increase military expenditures to foster economic growth (see also Gilmore 1999). This principle has been précised by Barney Frank: “These arguments will come from the very people who denied that the economic recovery plan created any jobs. We have a very odd economic philosophy in Washington: It’s called weaponized Keynesianism. It is the view that the government does not create jobs when it funds the building of bridges or important research or retrains workers, but when it builds airplanes that are never going to be used in combat, that is of course economic salvation.” Source URL: https://krugman.blogs.nytimes.com/2009/06/24/weaponized-keynesianism/. Noam Chomsky wrote extensively on the ubiquitous “militarization problem,” for instance in 1993 in an article in Z MAGAZINE (entitled: The Pentagon System): “Social spending may well arouse public interest and participation, thus enhancing the threat of democracy; the public cares about hospitals, roads, neighborhoods, and so on, but has no opinion about the choice of missiles and high-tech fighter planes. The defects of social spending do not taint the military Keynesian alternative, which had the added advantage that it was well-adapted to the needs of advanced industry: computers and electronics generally, aviation, and a wide range of related technologies and enterprises.”

  124. 124.

    The lecture was delivered on the 20th of March 1962 at the Berkeley Language Center. The original recording of the lecture can be found in the UCLA Library Digital Collections as tape 157a under the following URL: http://digital2.library.ucla.edu/viewItem.do?ark=21198/zz00253vz2&maxPageItems=999.

  125. 125.

    The Ancient Greek aphorism “know thyself” (one of the 147 Delphic maxims) is pertinent and some theorist hold that psychedelics were a quintessential spiritual catalyst in the “Eleusinian mysteries” (Bizzotto 2018; Wasson et al. 1979), a secret rite of passage which constituted a pivotal event in the lives of numerous Greek thinkers who deeply influenced the very basis of Western thought (among the initiates were with all likelihood eminent “lovers of wisdom” such as Socrates, Plato, Aristotle, Plotinus, and Cicero, i.a.). According to Plato, the ultimate purpose of the initiation was the “assimilation of divinity” and “to lead us back to the principles from which we descended” (Taylor et al. 1969, p. 368) or what Plotinus described as the “the flight of the alone to the alone,” an expression which echoes the Kaivalya Upanishad (kaivalya means liberation; but see Deussen 1906). It is interesting to consider Plato’s allegory of the cave this relation, e.g., the therein described immense difficulty to face the sun after lifelong imprisonment in a confined cell of false perception.

  126. 126.

    The Chinese logogram for the term “crisis” 危機 (pinyin: wēijī) is composed of “danger” 危and “opportunity” 機 (also “danger at a point of juncture” but the exact meaning is polysemous and a matter of debate among sinologists).

  127. 127.

    The concept of learned helplessness appears to be of relevance with respect to passivity and 5-HT1A agonism/antagonism (cf. Wu 1999).

  128. 128.

    For example, Immanuel Kant’s leitmotif Sapere aude (dare to think for yourself) which he used in his essay “Beantwortung der Frage: Was ist Aufklärung?” (Answering the Question: What Is Enlightenment?) from 1784.

  129. 129.

    As Bertrand Russel put it: “The whole duality of mind and matter [...] is a mistake; there is only one kind of stuff out of which the world is made, and this stuff is called mental in one arrangement, physical in the other.” (Russell 1913, p. 15). Russel’s monism stands in sharp contrast with the (mainly unquestioned) “reductive materialism” working hypothesis which forms the predominant basis of contemporary science.

  130. 130.

    Cf. Cartesian dualism and the Heisenberg cut (Atmanspacher 1997)

  131. 131.

    This view is gradually changing, for instance, Christof Koch stated in a 2014 Scientific America article that “the mental is too radically different for it to arise gradually from the physical” (p. 2), thereby highlighting the explanatory gap in contemporary neuroscientific theorizing.

  132. 132.

    “If at first the idea is not absurd, then there is no hope for it.” ~ Albert Einstein (as cited in Hermanns and Einstein 1983)

  133. 133.

    Transl.: “Times are changed; we, too, are changed within them.” In the context at hand, this implies that no ideology ever survived the test of time. Change is the only historical constant (a tautological statement evocative of the self-referential “Liar paradoxon” and Gödel’s incompleteness theorem).

  134. 134.

    Transl.: “The best of all possible worlds” in Essais de Théodicée sur la bonté de Dieu, la liberté de l’homme et l’origine du mal (Essays of Theodicy on the Goodness of God, the Freedom of Man and the Origin of Evil) published in 1710.

  135. 135.

    Mescaline (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic alkaloid in the phenethylamine class which was first isolated by the German pharmacologist and chemist in Arthur Heffter in 1897 who conducted self-experiments to compare mescaline with peyote (cf. Kauder 1899; Lewin 1894).

  136. 136.

    Radiocarbon dating of archeological specimens of peyote indicates that it has in all likelihood been used since prehistoric times as long as ≈ 5700 years ago (El-Seedi et al. 2005).

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Funding

This work was funded by the European Union Marie Curie Initial Training Network Marie Curie Actions: FP7-PEOPLE-2013-ITN-604764.

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Germann, C.B. 5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity. Act Nerv Super 61, 170–216 (2019). https://doi.org/10.1007/s41470-019-00063-y

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Keywords

  • 5-MeO-DMT
  • 5-HT2A agonism
  • Creativity
  • Nonduality
  • Anthropocene
  • Cognitive liberty
  • Neuroethics