Welcome to

Psilocybin-Research.com

Germann, C. B.(2019). The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Medical Hypotheses, 134, 1–9.

Plain numerical DOI: 10.1016/j.mehy.2019.109406
DOI URL
directSciHub download

Show/hide publication abstract

“We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has positive effects on genetic aging. ex hypothesi, we predict a priori that controlled therapeutic psilocybin interventions have quantifiable positive effects on leucocyte telomere length (telomeres are a robust predictor of mortality and various aging-related diseases). our hypothesising follows the popperian logic of scientific discovery, i.e., bold (and refutable) conjectures form the very foundation of scientific progress. the ‘psilocybin-telomere hypothesis’ is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., depression, anxiety, ptsd, addiction, etc.). additional support is based on a large corpus of studies which establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). another component of our argument is based on recent studies which demonstrate that ‘meditative states of consciousness’ exert beneficial effects on genetic aging (i.e., telomeric senescence). similarly, psilocybin can facilitate states of consciousness which are neurophysiologically and phenomenologically significantly congruent with meditative states. furthermore, prior research has demonstrated that a single dose of psilocybin can occasion profound and life changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). we postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that telomere analysis should be regularly included in future psilocybin studies to provide an adjunctive quantitative biological marker (viz., scientific consilience/methodological triangulation). in order to substantiate the ‘psilocybin-telomere hypothesis’ various potential neuropsychopharmacological and endocrinological mechanisms of action are discussed (e.g., hpa-axis reactivity, adult hippocampal neurogenesis, neurotropic gr…”

Full-text (*.pdf)
PubMed data (*.txt)
Русский

中文摘要

Smigielski, L., Scheidegger, M., Kometer, M., & Vollenweider, F. X. (2019). Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. NeuroImage, 196, 207–215.

Plain numerical DOI: 10.1016/j.neuroimage.2019.04.009
DOI URL
directSciHub download

Show/hide publication abstract

“Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. the analysis of functional connectivity identified psilocybin-related and mental state–dependent alterations in self-referential processing regions of the default mode network (dmn). notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. the extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior–posterior dmn connection. the study highlights the link between altered self-experience and subsequent behavioral changes. understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.”

Latest Update

Popik, P., Hogendorf, A., Bugno, R., Khoo, S. Y. S., Zajdel, P., Malikowska-Racia, N., … Golebiowska, J.. (2022). Effects of ketamine optical isomers, psilocybin, psilocin and norpsilocin on time estimation and cognition in rats. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-021-06020-5
DOI URL
directSciHub download

Show/hide publication abstract

“Rationale: ketamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. it is currently debatable whether these are essential for their therapeutic actions. as depressed patients report that the ‘time is dragging,’ we hypothesized that ketamine and psilocybin-like compounds may produce an opposite effect, i.e., time underestimation, purportedly contributing to their therapeutic properties. objectives: timing was tested following administration of (r)- and (s)-ketamine, and psilocybin, psilocin, and norpsilocin in the discrete-trial temporal discrimination task (tdt) in male rats. timing related to premature responses, and cognitive and unspecific effects of compounds were tested in the 5-choice serial reaction time task (5-csrtt) in the standard 1-s, and ‘easier’ 2-s stimulus duration conditions, as well as in the viti variant promoting impulsive responses. results: (s)-ketamine (15 but not 3.75 or 7.5 mg/kg) shifted psychometric curve to the right in tdt and reduced premature responses in 5-csrtt, suggesting expected time underestimation, but it also decreased the accuracy of temporal discrimination and increased response and reward latencies, decreased correct responses, and increased incorrect responses. while (r)-ketamine did not affect timing and produced no unspecific actions, it reduced incorrect responses in tdt and increased accuracy in 5-csrtt, suggesting pro-cognitive effects. psilocin and psilocybin produced mainly unspecific effects in both tasks, while norpsilocin showed no effects. conclusions: time underestimation produced by (s)-ketamine could be associated with its antidepressant effects; however, it was accompanied with severe behavioral disruption. we also hypothesize that behavioral disruption produced by psychedelics objectively reflects their psychotomimetic-like actions.”

Coppola, M., Bevione, F., & Mondola, R.. (2022). Psilocybin for Treating Psychiatric Disorders: A Psychonaut Legend or a Promising Therapeutic Perspective?. Journal of Xenobiotics

Plain numerical DOI: 10.3390/jox12010004
DOI URL
directSciHub download

Show/hide publication abstract

“Psychedelics extracted from plants have been used in religious, spiritual, and mystic practices for millennia. in 1957, dr. hofmann identified and synthesized the prodrug psilocybin, a substance present in more than 200 species of psychedelic mushrooms. although there were limitations related to the scientific design of many studies, clinical observations performed during the 1950s and 1960s showed a potential therapeutic effect of psilocybin for patients affected by depressive symptoms, anxiety, and conversion disorder. psilocybin was classed as a schedule i substance in 1970, but the fascination with psychedelics has remained almost unchanged over time, promoting a new scientific interest starting in the 1990s. recent studies have provided further evidence supporting the suggestive hypothesis of the therapeutic use of psilocybin for treating various psychiatric disorders, including pathological anxiety, mood depressive disorder, and addiction.”

McCulloch, D. E.-W., Grzywacz, M. Z., Madsen, M. K., Jensen, P. S., Ozenne, B., Armand, S., … Stenbæk, D. S.. (2022). Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report. Frontiers in Pharmacology

Plain numerical DOI: 10.3389/fphar.2022.841648
DOI URL
directSciHub download

Show/hide publication abstract

“ Psychedelic drugs such as psilocybin have shown substantial promise for the treatment of several psychiatric conditions including mood and addictive disorders. they also have the remarkable property of producing persisting positive psychological changes in healthy volunteers for at least several months. in this study (nct03289949), 35 medium-high doses of psilocybin were administered to 28 healthy volunteers (12 females). by the end of the dosing day, participants reported the intensity of their acute experience using the 30-item mystical experience questionnaire (meq) and an open-form qualitative report from home. persisting psychological effects attributed to the psilocybin experience were measured using the persisting effects questionnaire (peq) 3-months after administration. using a linear latent-variable model we show that the meq total score is positively associated with the later emergence of positive peq effects ( p = 3 × 10 −5 ). moreover, the meq subscales ‘positive mood’ ( p corr = 4.1 × 10 −4 ) and ‘mysticality’ ( p corr = 2.0 × 10 −4 ) are associated with positive peq whereas the subscales ‘transcendence of time and space’ ( p corr = 0.38) and ‘ineffability’ ( p corr = 0.45) are not. using natural language pre-processing, we provide the first qualitative descriptions of the ‘complete mystical experience’ induced by orally administered psilocybin in healthy volunteers, revealing themes such as a sense of connection with the universe, familial love, and the experience of profound beauty. combining qualitative and quantitative methods, this paper expands understanding of the acute psilocybin induced experience in healthy volunteers and suggests an importance of the type of experience in predicting lasting positive effects. ”

Kisely, S., Connor, M., Somogyi, A. A., & Siskind, D.. (2022). A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders. Australian and New Zealand Journal of Psychiatry

Plain numerical DOI: 10.1177/00048674221083868
DOI URL
directSciHub download

Show/hide publication abstract

“Objectives: there is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. although there have been several recent systematic reviews, study and participant numbers have been limited, and the field is rapidly evolving with the publication of more studies. we therefore conducted a systematic review of pubmed, medline, psycinfo, the cochrane central register of controlled trials, embase, and cinahl for randomised controlled trials of methylenedioxymethamphetamine and psilocybin with either inactive or active controls. methods: outcomes were psychiatric symptoms measured by standardised, validated and internationally recognised instruments at least 2 weeks following drug administration, quality was independently assessed using the cochrane risk of bias assessment tool and grading of recommendations assessment, development and evaluation framework. results: there were eight studies on methylenedioxymethamphetamine and six on psilocybin. diagnoses included post-traumatic stress disorder, long-standing/treatment-resistant depression, obsessive-compulsive disorder, social anxiety in adults with autism, and anxiety or depression in life-threatening disease. the most information and strongest association was for the change in methylenedioxymethamphetamine scores compared to active controls in post-traumatic stress disorder (k = 4; standardised mean difference = −0.86; 95% confidence interval = [−1.23, −0.50]; p < 0.0001). there were also small benefits for social anxiety in adults with autism. psilocybin was superior to wait-list but not niacin (active control) in life-threatening disease anxiety or depression. it was equally as effective as escitalopram in long-standing depression for the primary study outcome and superior for most of the secondary outcomes in analyses uncorrected for multiple comparisons. both agents were well tolerated in supervised trials. trial quality varied with only small proportions of potential participants included in the randomised phase. overall certainty of evidence was low or very low using the grading of recommendations assessment, development and evaluation framework. conclusion: methylenedioxymethamphetamine and psilocybin may show promise in highly selected populations when administered in closely supervised settings and with intensive support.”

Van Court, R. C., Wiseman, M. S., Meyer, K. W., Ballhorn, D. J., Amses, K. R., Slot, J. C., … Uehling, J. K.. (2022). Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development. Fungal Biology

Plain numerical DOI: 10.1016/j.funbio.2022.01.003
DOI URL
directSciHub download

Show/hide publication abstract

“Therapeutic use of psilocybin has become a focus of recent international research, with preliminary data showing promise to address a range of treatment-resistant mental health conditions. however, use of psilocybin as a healing entheogen has a long history through traditional consumption of mushrooms from the genus psilocybe. the forthcoming adoption of new psilocybin-assisted therapeutic practices necessitates identification of preferred sources of psilocybin; consequently, comprehensive understanding of psilocybin-containing fungi is fundamental to consumer safety. here we examine psilocybin producing fungi, discuss their biology, diversity, and ethnomycological uses. we also review recent work focused on elucidation of psilocybin biosynthetic production pathways, especially those from the genus psilocybe, and their evolutionary history. current research on psilocybin therapies is discussed, and recommendations for necessary future mycological research are outlined.”

Li, N. X., Hu, Y. R., Chen, W. N., & Zhang, B.. (2022). Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. Journal of Affective Disorders

Plain numerical DOI: 10.1016/j.jad.2021.09.041
DOI URL
directSciHub download

Show/hide publication abstract

“Background: previous studies have shown that psilocybin has antidepressant effects. in the current study, we aim to explore the dose effects of psilocybin on primary (major depression patients) and secondary depression (depressed cancer patients). methods: published studies concerning psilocybin for depression were retrieved. in accordance with prisma guidelines, 6 databases (pubmed, embase, web of science, cochrane library, clinicaltrials.gov 2.3 and wanfang database) were searched for research studies published or still in progress from inception to 30 november, 2020, with language restricted to english and chinese. hedges’ g of beck depression inventory (bdi) score changes was calculated as the primary outcome. results: 7 articles were finally included, with a total of 136 participants. in terms of efficacy, hedges’ g was 1.289 (95%ci=[1.020, 1.558], heterogeneity i2=50.995%, p<0.001). as psilocybin dose increases within a certain range, the antidepressive effect declines and then increases, with 30-35 mg/70 kg achieving the optimal therapeutic effect. subgroup analysis suggested that the antidepressive effect of psilocybin was extremely significant at a relatively high dose (30-35mg/70kg: hedges’ g=3.059, 95%ci=[2.269, 3.849], p<0.001), long-term (>1month: hedges’ g=1.123, 95%ci=[0.861, 1.385], p<0.001) and when used in primary depression patients (hedges’ g=2.190, 95%ci=[1.423, 2.957], p<0.001). limitations: only a small number of studies can be identified of variable quality, thus our conclusions remain preliminary. conclusions: our preliminary results have shown that psilocybin exerts a rapid effect in reducing depressive symptom on primary and secondary depression. the optimal dose of psilocybin may be 30-35mg/70kg or higher; future clinical trials are warranted for further evaluation on its effect.”

Barrett, F. S., Zhou, Y., Carbonaro, T. M., Roberts, J. M., Smith, G. S., Griffiths, R. R., & Wong, D. F.. (2022). Human Cortical Serotonin 2A Receptor Occupancy by Psilocybin Measured Using [11C]MDL 100,907 Dynamic PET and a Resting-State fMRI-Based Brain Parcellation. Frontiers in Neuroergonomics

Plain numerical DOI: 10.3389/fnrgo.2021.784576
DOI URL
directSciHub download

Show/hide publication abstract

“ Psilocybin (a serotonin 2a, or 5-ht 2a , receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. the current report utilized positron emission tomography (pet) with the selective 5-ht 2a receptor inverse agonist radioligand [ 11 c]mdl 100,907 (a.k.a. m100,907) and cortical regions of interest (rois) derived from resting-state functional connectivity-based brain parcellations in 4 healthy volunteers (2 females) to determine regional occupancy/target engagement of 5-ht 2a receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). average 5-ht 2a receptor occupancy across all rois was 39.5% (± 10.9% sd). three of the rois with greatest occupancy (between 63.12 and 74.72% occupancy) were within the default mode network (subgenual anterior cingulate and bilateral angular gyri). however, marked individual variability in regional occupancy was observed across individuals. these data support further investigation of the relationship between individual differences in the acute and enduring effects of psilocybin and the degree of regional 5-ht 2a receptor occupancy. ”

Hase, A., Erdmann, M., Limbach, V., & Hasler, G.. (2022). Analysis of recreational psychedelic substance use experiences classified by substance. Psychopharmacology

Plain numerical DOI: 10.1007/s00213-022-06062-3
DOI URL
directSciHub download

Show/hide publication abstract

“Rationale and objectives: differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. quantitative linguistic analysis is a powerful tool to examine such differences. this study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports. methods: using 2947 publicly available online reports, we compared ayahuasca and n,n-dimethyltryptamine (dmt, analyzed together), ketamine, lysergic acid diethylamide (lsd), 3,4-methylenedioxymethamphetamine (mdma), psilocybin (mushroom), and antidepressant drug use experiences. we examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales. results: linguistic markers of psychological function indicated distinct effect profiles. for example, mdma experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. in contrast, ayahuasca and dmt experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. lsd, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language. conclusion: this article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. the large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. the results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems.”

Miceli McMillan, R., & Jordens, C.. (2022). Psychedelic-assisted psychotherapy for the treatment of major depression: a synthesis of phenomenological explanations. Medicine, Health Care and Philosophy

Plain numerical DOI: 10.1007/s11019-022-10070-7
DOI URL
directSciHub download

Show/hide publication abstract

“Psychedelic-assisted psychotherapy (pap) combines the use of psychedelic compounds, such as psilocybin, with psychotherapy. pap has shown some promise as a novel treatment for major depressive disorder (mdd), and empirical research suggests that its efficacy turns on the altered states induced by psychedelic compounds. in this paper we draw on the literature of phenomenology to explain the therapeutic potential of psychedelic experiences. svenaeus characterises mental illness as a form of suffering that entails three distinct but related experiences of alienation or ‘unhomelike being-in-the-world’: (1) illness suffering, which relates to embodiment; (2) existential suffering, which relates to self-narratives, and (3) political suffering, which relates to social relationships. ratcliffe further characterises the experience of mdd in phenomenological terms as a loss of pre-intentional possibility that manifests as excessive noematic feeling in the experience of embodiment, restrictive narratives in the construction of self, and disconnectedness in experience of the social world. we contend that pap ameliorates the suffering associated with mdd by inducing and consolidating a state of broadened pre-intentional possibility—one that entails sudden, profound and enduring changes in embodiment, self-narratives, and social experience. we argue further that this phenomenological account is consistent with a bio-psycho-social model of mental health and illness, and we frame it as an argument supporting the plausibility of recent claims about treatment success. this helps to justify ongoing future empirical research in this setting.”

Gründer, G., Brand, M., Kärtner, L., Scharf, D., Schmitz, C., Spangemacher, M., & Mertens, L. J.. (2022). Are psychedelics fast acting antidepressant agents?. Nervenarzt

Plain numerical DOI: 10.1007/s00115-021-01255-1
DOI URL
directSciHub download

Show/hide publication abstract

“Background: psychedelics, such as psilocybin represent one of the most promising current therapeutic approaches in psychiatry. objective: psychedelics seem to have not only potent antidepressant effects. do they also work particularly quickly, i.e. within one day? material and methods: the available literature on clinical studies of psychedelics in depressive syndromes is presented both from the period up to the prohibition of these substances in the late 1960s as well as after the resumption of research in the 2000s. one focus is the speed of onset of antidepressant action. results: only the clinical studies published since 2016 that meet modern methodological standards have also systematically examined the speed of the antidepressant onset of action. the published studies, which were almost exclusively carried out with psilocybin, so far show small sample sizes (the total number of patients with depression treated in published clinical studies is < 200) and some of them have methodological weaknesses; however, they suggest a pronounced and very rapid onset of action within one day for depression, treatment-resistant depression and depression in the context of life-threatening cancer. conclusion: the available studies indicate a potent, rapid onset and in many cases long-lasting antidepressant effect over several months. the currently conducted studies with three-digit patient numbers will provide final information about the potential of psilocybin for depression.”

Kargbo, R. B., Sherwood, A. M., Meisenheimer, P., Lenoch, K., & Abebe, S.. (2022). Psilocybin: Characterization of the metastable zone width (MSZW), control of anhydrous polymorphs, and particle size distribution (PSD). ACS Omega

Plain numerical DOI: 10.1021/acsomega.1c06708
DOI URL
directSciHub download

Show/hide publication abstract

“Psilocybin, a serotonergic agonist, was granted a ‘breakthrough therapy’ status by the food and drug administration for clinical trials involving major depressive disorder and treatment-resistant depression. the direct phosphorylation of psilocin to psilocybin that uses a fast crystallization associated with a kinetically controlled process resulted in a smaller particle size distribution. herein, the measurement of the metastable zone width (mszw) and nucleation induction enabled a thermodynamically controlled crystallization process, which leads to the formation of a crystal structure with stronger interactions, controlled particle size distribution (psd), and improved impurity profile. employing a high-resolution inline microscopy viewer allowed the real-time monitoring of the crystallization process and the measurement of the particle size. we also present a comprehensive study of the formation of polymorph b (trihydrate), polymorph a (anhydrate), and polymorph h (anhydrate) using water recrystallization, which indicates that the formation of polymorph b (trihydrate) is independent of the crystallization method. however, polymorphs a and h are dependent on the mode of drying: drying at room temperature under vacuum gives rise to mainly polymorph a, and when heated even at relatively low temperatures, a mixture of polymorphs a and h beings to form.”

Sarris, J., Rubiano, D. P., Day, K., Galvao-Coelho, N. L., & Perkins, D.. (2022). Psychedelic medicines for mood disorders: Current evidence and clinical considerations. Current Opinion in Psychiatry

Plain numerical DOI: 10.1097/YCO.0000000000000759
DOI URL
directSciHub download

Show/hide publication abstract

“Purpose of review despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions. recent findings serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling n,n-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (mdma) has been used effectively to treat posttraumatic stress disorder (ptsd), with phase iii clinical trial evidence. microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood. summary current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. however, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive phase iii studies (aside from mdma for ptsd). further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.”

About Psilocybin-Research.com

Machine Learning Powered AI Translation

Benefiting society| Improving healthcare | Increasing knowledge | Exploring new Horizons

Psilocybin-Research is a research spin-off that emerged from the European Union funded Marie Curie Actions CogNovo program located at the University of Plymouth (United Kingdom).

The founder of Psilocybin-Research is Dr. Christopher B. Germann. The subsequent section provides a prefatory statement by Dr. Germann.
You can alternatively display/download the statement as a LaTeX PDF (opens in a new window) or HTML5 document (integrated AI text-to-speech synthesis)

A psychophysical analogy between psychoactive tryptamines and radioactive isotopes

“Given the significant wicked problems humanity is forced to face in the 21^st century Anthropocene, systematic transdisciplinary scientific research on various naturally-occurring “consciousness expanding” psychoactive substances (specifically in the domain of psychology and neuroscience) is, per analogiam, at least as important as basic research on radioactive substances was for the progress of the physical sciences in the 20^th century. Research on psychoactive tryptamines could potentially revolutionize our understanding of psychology comparable to the way research on radioactive isotopes revolutionized our understanding of physics. Today’s existential problems are primarily caused by a “mass-pathology of consciousness”. Therefore, “looking inside” (introspection/psychology) is currently much more important than “looking outside” (extrospection/physics). Contrary to wide spread believe, technological solution will not solve our problems which are clearly caused by psychological corruption (a fact which is not easily admitted due to unconscious psychological defense mechanism which prevent an unbiased perception of the real causes of our extremely pressing problems). A deeper understanding of consciousness might simultaneously help to address external problems as inside and outside might not be separable in the Cartesian dualistic sense (viz., the dichotomy between mind and matter, psyche and physis, subject and object, might not be as clear-cut as mainstream science prima facie assumes). Intrinsically motivated, authentic, and non-conformist thinking à la Marie Curie is of crucial importance in this context. Currently, we are utterly nescient about the exact relationship between mind and matter (i.e., psyche and physis; cf. the hitherto unresolved explanatory gap). Ergo, intellectual/epistemological humility is a true scientific virtue which forms the basis of genuine curiosity, and hence creativity, innovation, evolution, and the urgently needed radical Kuhnian paradigm-change. Specifically the potential to induce transformative and enduring states of unity consciousness (s.c., nonduality/Advaita) is of great pertinence in the prevailing capitalistic neoliberal/social-Darwinian climate which indoctrinates immoral/inhuman hyper-competition, careerism, ego-centrism, and psychopathic narcissism (this is then called “success”). Utilized in the right way, minute quantities of a chemically well-defined small class of psychoactive tryptamines (i.e., structural analogues of psilocybin/serotonin) can change human consciousness in profound ways and facilitate deep ontological insights into the interconnectedness of humanity (beyond economic competition) and all of nature (biophilia versus nécrophilia; cf. hologenome theory of evolution). Given that converging evidence from a variety of independent sources indicates that humanity is currently destroying the ecosystem at an exponential rate, a fundamental shift in the regnant cognitive modus operandi is of pivotal importance for the survival of the species homo sapiēns (currently more accurately classified as homo consumens) on this planet which has been termed spaceship earth. Contrary to widespread naiveté, the logical interpretation of this proposal does not rest on the premise that every individual has to partake in this mind-changing endeavor. From a complex systems theory point of view, a phase-shift in the collective unconscious of the species (à la C.G. Jung) might be induced if a proportionally rather small ‘critical mass’ of participants is reached (cf. ‘snowball-effect’ in social psychology, i.e., “spreading activation” in communication networks). We simply do not know enough about consciousness (and de facto physical matter; cf. recent empirical findings in experimental quantum entanglement research, e.g., violations of Bell inequalities; hypothetical dark matter & dark energy, extra dimension/M-theory, etc. pp.) to precluded the possibility of effecting the collective unconscious in hitherto unknown ways prima facie (a close-minded and dogmatic attitude towards the possibilities of science which is unfortunately very dominant in indoctrinated mainstream academic circles). For instance, we find similar models in developmental biology where a small minority of so called ‘imaginal cells’ in the developing chrysalis transform the whole organism beyond recognition into a beautiful colorful butterfly which can fly! Who would have predicted this unfoldment of inherent (dormant) potential a priori? Open-mindedness is a condicio sine qua non for creativity, cognitive innovation and, ergo, scientific progress and and the theoretically infinite unfoldment of human potential.”
~ Dr. Christopher B. Germann (Marie Curie Alumnus)

See also Dr. Germann’s thematically related papers on N,N-DMT and 5-MeO-DMT (both compounds are structural relatives of psilocybin/4-PO-HO-DMT):

Further information on the various 'building blocks' of this multifaceted statement

Wicked problems

The Anthropocene epoch

Hologenome theory of evolution

The explanatory gap

Imaginal cells

Spaceship Earth

https://cognitive-liberty.online/tavistock-institute-for-human-relations/
https://cognitive-liberty.online/studies-on-the-financial-power-elite-behind-the-facade-of-democracy/

Erritzoe, D., Roseman, L., Nour, M. M., MacLean, K., Kaelen, M., Nutt, D. J., & Carhart-Harris, R. L.. (2018). Effects of psilocybin therapy on personality structure. Acta Psychiatrica Scandinavica

, 138(5), 368–378.
Plain numerical DOI: 10.1111/acps.12904
DOI URL
directSciHub download

Show/hide publication abstract

“Objective to explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (trd). method twenty patients with moderate or severe, unipolar, trd received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. personality was assessed at baseline and at 3-month follow-up using the revised neo personality inventory (neo-pi-r), the subjective psilocybin experience with altered state of consciousness (asc) scale, and depressive symptoms with qids-sr16. results neuroticism scores significantly decreased while extraversion increased following psilocybin therapy. these changes were in the direction of the normative neo-pi-r data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. openness scores also significantly increased following psilocybin, whereas conscientiousness showed trend-level increases, and agreeableness did not change. conclusion our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in extraversion and openness might constitute an effect more specific to psychedelic therapy. this needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.”

'The hidden Self' by William James (1890)

“Round about the accredited and orderly facts of every science there ever floats a sort of dust-cloud of exceptional observations, of occurrences minute and irregular, and seldom met with, which it always proves less easy to attend to than to ignore. The ideal of every science is that of a closed and completed system of truth. The charm of most sciences to their more passive disciples consists in their appearing, in fact, to wear just this ideal form. Each one of our various ‘ologies’ seems to offer a definite head of classification for every possible phenomenon of the sort which it professes to cover; and, so far from free is most men’s fancy, that when a consistent and organized scheme of this sort has once been comprehended and assimilated, a different scheme is unimaginable. No alternative, whether to whole or parts, can any longer be conceived as possible. Phenomena unclassifiable within the system are therefore paradoxical absurdities, and must be held untrue. When, moreover, as so often happens, the reports of them are vague and indirect, when they come as mere marvels and oddities rather than as things of serious moment, one neglects or denies them with the best of scientific consciences. Only the born geniuses let themselves be worried and fascinated by these outstanding exceptions, and get no peace till they are brought within the fold. Your Galileos, Galvanis, Fresnels, Purkinjes, and Darwins are always getting confounded and troubled by insignificant things. Anyone will renovate his science who will steadily look after the irregular phenomena. And when the science is renewed, its new formulas often have more of the voice of the exceptions in them than of what were supposed to be the rules. No part of the unclassed residuum has usually been treated with a more contemptuous scientific disregard than the mass of phenomena generally called mystical. Physiology will have nothing to do with them. Orthodox psychology turns its back upon them. Medicine sweeps them out; or, at most, when in an anecdotal vein, records a few of them as ‘effects of the imagination’ a phrase of mere dismissal whose meaning, in this connection, it is impossible to make precise. All the while, however, the phenomena are there, lying broadcast over the surface of history. No matter where you open its pages, you find things recorded under the name of divinations, inspirations, demoniacal possessions, apparitions, trances, ecstasies, miraculous healings and productions of disease, and occult powers possessed by peculiar individuals over persons and things in their neighborhood. […] To no one type of mind is it given to discern the totality of Truth. Something escapes the best of us, not accidentally, but systematically, and because we have a twist. The scientific-academic mind and the feminine-mystical mind shy from each other’s facts, just as they shy from each other’s temper and spirit. Facts are there only for those who have a mental affinity with them. When once they are indisputably ascertained and admitted, the academic and critical minds are by far the best fitted ones to interpret and discuss them – for surely to pass from mystical to scientific speculations is like passing from lunacy to sanity; but on the other hand if there is anything which human history demonstrates, it is the extreme slowness with which the ordinary academic and critical mind acknowledges facts to exist which present themselves as wild facts with no stall or pigeon-hole, or as facts which threaten to break up the accepted system. In psychology, physiology, and medicine, wherever a debate between the Mystics and the Scientifics has been once for all decided, it is the Mystics who have usually proved to be right about the facts, while the Scientifics had the better of it in respect to the theories.”
(James, 1890, pp. 361–362)

hubble-deep-field-nasa

Psilocybin-Research.com

Looking Deep Inside...

Beckwith, S. V. W., Stiavelli, M., Koekemoer, A. M., Caldwell, J. A. R., Ferguson, H. C., Hook, R., … Sosey, M.. (2006). The Hubble Ultra Deep Field. The Astronomical Journal

, 132(5), 1729–1755.
Plain numerical DOI: 10.1086/507302
DOI URL
directSciHub download

Show/hide publication abstract

“This paper presents the hubble ultra deep field (hudf), a 1 million s exposure of an 11 arcmin2region in the southern sky with the advanced camera for surveys on the hubble space telescope using director’s discretionary time. the exposure time was divided among four filters, f435w (b435), f606w (f606), f775w (i775), and f850lp (z850), to give approximately uniform limiting magnitudes mab∼ 29 for point sources. the image contains at least 10,000 objects, presented here as a catalog, the vast majority of which are galaxies. visual inspection of the images shows few if any galaxies at redshifts greater than ∼4 that resemble present-day spiral or elliptical galaxies. the image reinforces the conclusion from the original hubble deep field that galaxies evolved strongly during the first few billion years in the infancy of the universe. using the lyman break dropout method to derive samples of galaxies at redshifts between 4 and 7, it is possible to study the apparent evolution of the galaxy luminosity function and number density. examination of the catalog for dropout sources yields 504 s435dropouts, 204 v606dropouts, and 54 i775dropouts. the i775dropouts are most likely galaxies at redshifts between 6 and 7. using these samples, which are at different redshifts but derived from the same data, we find no evidence for a change in the characteristic luminosity of galaxies but some evidence for a decrease in their number densities between redshifts of 4 and 7. assessing the factors needed to derive the luminosity function from the data suggests that there is considerable uncertainty in parameters from samples discovered with different instruments and derived using independent assumptions about the source populations. this assessment calls into question some of the strong conclusions of recently published work on distant galaxies. the ultraviolet luminosity density of these samples is dominated by galaxies fainter than the characteristic luminosity, and the hudf reveals considerably more luminosity than shallower surveys. the apparent ultraviolet luminosity density of galaxies appears to decrease from redshifts of a few to redshifts greater than 6, although this decrease may be the result of faint-end incompleteness in the most distant samples. the highest redshift samples show that star formation was already vigorous at the earliest epochs at which galaxies have been observed, less than 1 billion years after the big bang. © 2006. the american astronomical societ…”

The interdisciplinary CogNovo program

The primary foci of CogNovo are the neuronal correlates and psychological mechanisms which underpin creativity, with interdisciplinary investigations into the rôle of creativity in human cognition, and their application in sustainable technological developments and social innovation. The program has been funded by the European Union as part of the Framework Programmes for Research and Technological Development.
(FP7-PEOPLE-2013-ITN-604764).

https://cognovo.eu

https://cognovo.net

Legal disclaimer: The interdisciplinary Marie Curie CogNovo program has been intentionally designed by the European Union and the University of Plymouth (United Kingdom) to discuss and disseminate a wide view on a diverse spectrum of topics including psychology, neuroscience, current affairs, basic science, humanities, and the arts, inter alia. Note that the views and opinions expressed on this website do not necessarily represent the opinions of any of the institutions mentioned on this website and belong exclusively to the copyright holder. The CogNovo program explicitly emphasises cognitive and social innovation, the generation of new ideas and perspectives, and the probing of boundaries, but see https://www.cognovo.eu/about/

The neuro-cognitive effects of psilocybin

Cognitive Neuroscience

TED talk by Prof. Roland Griffith (John Hopkins)
https://www.hopkinsmedicine.org/profiles/results/directory/profile/1311852/roland-griffiths

Research on psilocybin & creativity

Spitzer, M., Thimm, M., Hermle, L., Holzmann, P., Kovar, K.-A., Heimann, H., … Schneider, F.. (1996). Increased activation of indirect semantic associations under psilocybin. Biological Psychiatry, 39(12), 1055–1057.

Plain numerical DOI: 10.1016/0006-3223(95)00418-1
DOI URL
directSciHub download

Show/hide publication abstract

“The finding that psilocybin increases indirect semantic priming in normal subjects adds to our general understanding of the effects of hallucinogenic agents on cognitive functions. from anecdotal records and very few controlled studies these agents are believed to have subjective effects that sometimes are referred to as ‘broadening consciousness’ and ‘enhancing cre- ativity’ (references in pletscher and ladewig 1994). although most objective measures have failed to support these claims, our data suggest that the agent in fact leads to an increased avail- ability of remote associations and thereby may bring cognitive contents to mind that under normal circumstances remain non- activated; however, the generally decreased psychological per- formance under hallucinogenic agents suggests that the increased indirect priming effect is due to a decreased capacity to use contextual information for the focusing of semantic processing. hence, subjectively experienced increases in creativity as well as the broadening of consciousness have been found to parallel decreases in objective performance measures. from a methodological perspective, our data indicate that indirect semantic priming is a highly sensitive measure that appears to respond not only to pharmacologic intervention, but also to the psychological effects of the setting of the study. the following post hoc suggestion may account for the finding of consistent (though nonsignificant) increases of priming effects under placebo. it is noteworthy that before testing, subjects appeared anxious, tight, and tense, a state known to produce stereotyped verbal associations and decreased priming effects (cf. spitzer 1995). when about 30-40 min after drug intake the subject became aware of either being on placebo or being on psilocybin, they tended to become more relaxed and unwinding, which is a state known to facilitate access to a wider scope of associative material. this is a testable hypothesis and we currently plan to use indirect semantic priming to investigate several nonpharmacologically induced states of anxiety and general arousal. in conclusion, we have demonstrated the effect of a halluci- nogenic agent, known to affect the 5-ht system, on the spread of activation during lexical access. this may serve as an example of how subjective psychopathology, objective psychological mea- surements, and underlying brain physiology (viz., neuromodula- tion) can be linked within a single conceptual framework.”

Kuypers, K. P. C.. (2018). Out of the box: A psychedelic model to study the creative mind. Medical Hypotheses, 115, 13–16.

Plain numerical DOI: 10.1016/j.mehy.2018.03.010
DOI URL
directSciHub download

Show/hide publication abstract

“Our creativity is challenged daily when facing new situations asking for novel solutions. creativity, a multicomponent construct includes flexible divergent and rigid convergent thinking. psychedelic drugs like psilocybin can enhance creativity and affect state of mind (mood, empathy, openness). of note, flexible thinking is disturbed in psychopathological conditions like anxiety disorders and depression and preliminary findings have shown psychedelics to be efficacious in the treatment of those conditions. the question how psychedelics induce this state of enhanced flexible thinking remains to be answered and investigating the neurobiology underlying this phenomenon will not only help in understanding why psychedelics are of use in the therapeutic setting but also in other settings where flexible thinking is challenged. a model including neuronal networks, neurotransmitters and personal factors playing a role in this process will be proposed which can be put to the test by means of placebo-controlled pharmaco-imaging studies in healthy volunteers. copyright © 2018 the author”

Prochazkova, L., Lippelt, D. P., Colzato, L. S., Kuchar, M., Sjoerds, Z., & Hommel, B.. (2018). Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology, 235(12), 3401–3413.

Plain numerical DOI: 10.1007/s00213-018-5049-7
DOI URL
directSciHub download

Show/hide publication abstract

“Introduction taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-ht 2a receptors and promoting cognitive flexibility, crucial to creative thinking. nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults. methods during a microdosing event organized by the dutch psychedelic society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the picture concept task assessing convergent thinking and the alternative uses task assessing divergent thinking. a short version of the ravens progressive matrices task assessed potential changes in fluid intelligence. we tested once before taking a microdose and once while the effects were expected to be manifested. results we found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected. conclusion while this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. we hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.”

Show additional publications on psilocybin & creativity

Psilocybin_increases_creativity_via ego_dissolution_and_Openness_to_Experience-A_synopsis_and_hypothesis_by_Christopher_B_Germann

For further information on the “ego-dissolution/creativity hypothesis” see:

Germann, C. B.. (2019). 5-methoxy-N,N-dimethyltryptamine: An ego-dissolving endogenous neurochemical catalyst of creativity. BioRxiv

Plain numerical DOI: 10.1101/578435
DOI URL
directSciHub download

Show/hide publication 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 (which is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions, e.g., advaita vedānta, mahāyāna buddhism). 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 scientific research, however, its remarkable psychoactivity is presumably mediated via agonism of the 5-ht2a (serotonin) receptor subtype. anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-meo-dmt containing plants for medicinal, psychological, and spiritual purposes for millennia. in this paper we argue that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool which has the potential to significantly advance our understanding of the cognitive and neuronal processes which underpin cognition and creativity. an eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of this conjecture. specifically, we suggest that 5-meo-dmt has great potential in this respect due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz.., ego death). in addition, 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 discussed (particularly in the context of military torture).”

Psilocybin reduces depression

: Source: https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fs41598-017-13282-7/MediaObjects/41598_2017_13282_Fig1_HTML.jpg

Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … Nutt, D. J.. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports

, 7(1), 13187.
Plain numerical DOI: 10.1038/s41598-017-13282-7
DOI URL
directSciHub download

Show/hide publication abstract

“© 2017 the author(s). psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. here, cerebral blood flow (cbf) and blood oxygen-level dependent (bold) resting-state functional connectivity (rsfc) were measured with functional magnetic resonance imaging (fmri) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (trd). quality pre and post treatment fmri data were collected from 16 of 19 patients. decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. whole-brain analyses revealed post-treatment decreases in cbf in the temporal cortex, including the amygdala. decreased amygdala cbf correlated with reduced depressive symptoms. focusing on a priori selected circuitry for rsfc analyses, increased rsfc was observed within the default-mode network (dmn) post-treatment. increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex rsfc was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex rsfc. these data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. the post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. a ‘reset’ therapeutic mechanism is proposed.”

Compare

Flaherty, A. W.. (2011). Brain illness and creativity: Mechanisms and treatment risks. Canadian Journal of Psychiatry

Plain numerical DOI: 10.1177/070674371105600303
DOI URL
directSciHub download

Show/hide publication abstract

“Brain diseases and their treatment may help or hurt creativity in ways that shape quality of life. increased creative drive is associated with bipolar disorder, depression, psychosis, temporal lobe epilepsy, frontotemporal dementia, parkinson disease treatments, and autism. creativity depends on goal-driven approach motivation from midbrain dopaminergic systems. fear-driven avoidance motivation is of less aid to creativity. when serotonin and norepinephrine lower motivation and flexible behaviour, they can inhibit creativity. hemispheric lateralization and frontotemporal connections must interact to create new ideas and conceptual schemes. the right brain and temporal lobe contribute skill in novelty detection, while the left brain and frontal lobe foster approach motivation and more easily generate new patterns of action from the novel perceptions. genes and phenotypes that increase plasticity and creativity in tolerant environments with relaxed selection pressure may confer risk in rigorous environments. few papers substantively address this important but fraught topic. antidepressants (ads) that inhibit fear-driven motivation, such as selective serotonin reuptake inhibitors, sometimes inhibit goal-oriented motivation as well. ads that boost goal-directed motivation, such as bupropion, may remediate this effect. benzodiazepines and alcohol may be counterproductive. although dopaminergic agonists sometimes stimulate creativity, their doing so may inappropriately disinhibit behaviour. dopamine antagonists may suppress creative motivation; lithium and anticonvulsant mood stabilizers may do so less. physical exercise and rem sleep may help creativity. art therapy and psychotherapy are not well studied. preserving creative motivation can help creativity and other aspects of well-being in all patients, not just artists or researchers.”

Psilocybin enhances functional connectivity in the brain

Neuronal interconnectivity

Abstract: Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about howthey work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normalwaking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/ functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.

Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., … Nutt, D. J.. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138–2143.

Plain numerical DOI: 10.1073/pnas.1119598109
DOI URL
directSciHub download

Show/hide publication abstract

“Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about howthey work in the brain. here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional mri (fmri) protocol designed to capture the transition from normalwaking consciousness to the psychedelic state. arterial spin labeling perfusion and blood-oxygen level-dependent (bold) fmri were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with bold. as predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and bold signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (acc and pcc). decreased activity in the acc/medial prefrontal cortex (mpfc) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. based on these results, a seed-based pharmaco-physiological interaction/ functional connectivity analysis was performed using a medial prefrontal seed. psilocybin caused a significant decrease in the positive coupling between the mpfc and pcc. these results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain’s key connector hubs, enabling a state of unconstrained cognition.”