![5-HT 2A R in Visual cortex From Zilles, et al. (2002), reproduced with permission. See also Beliveau, et al. (2017) and Watakabe, et al. (2008). Distribution of serotoninergic 5-HT 2A receptors in human occipital cortex ([3H]ketanserin binding sites). The color-coding indicates receptor densities in fmol/mg protein. The filled arrowheads indicate borders of cortical areas, the white arrowhead contours indicate the borders of subareas r (rim region) within V1, and OBγ (border tuft region) within V2. p-o, Parieto-occipital sulcus; V1, primary visual cortex; V2d, dorsal part of the secondary visual cortex; V2v, ventral part of the secondary visual cortex.](https://www.researchgate.net/profile/Leor-Roseman/publication/337388866/figure/fig5/AS:827252614914048@1574243801119/5-HT-2A-R-in-Visual-cortex-From-Zilles-et-al-2002-reproduced-with-permission-See_Q320.jpg)
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Functional imaging investigation of psychedelic visual imagery
Abstract and Figures
Psychedelics can induce eyes-closed imagery in which various visions can be experienced. These visions vary from simple geometrical patterns, to more complex imagery, to full immersion within “other realms”. Past studies suggest that the visual cortex is involved in processing these visions, yet these studies were limited into investigation of activity. In this thesis, the aim was to expand on the involvement of the visual cortex by investigating processes that are beyond simple activation maps, such as functional connectivity and dynamics. In study 1, it was hypothesized that the visual cortex will show increased functional connectivity with many cortical and subcortical regions. This was investigated with 15 subjects that were scanned using fMRI under the influence of 75 µg of LSD or placebo. The results of this study showed increased resting state functional connectivity (RSFC) between the primary visual cortex and many cortical and subcortical regions. This result correlated with subjective ratings of psychedelic imagery and with occipital alpha power suppression measured with MEG, which is a reliable neural correlate of the intensity of the psychedelic state. It study 2, it was hypothesized that connectivity within the visual cortex would match its retinotopic architecture. Retinotopic mapping is the representation of the visual field (the world we observe) in the visual cortex – e.g. areas which are near to each other in the visual field will be near each other in the visual cortex. In this study, it was found that under LSD (same procedure as study 1), with eyes closed, connectivity patterns between different subregions of the visual cortex matched the retinotopic mapping of these regions, suggesting that the visual system behaves as if it is seeing spatially localized input, with eyes-closed under LSD. In study 3, it was hypothesized that during the onset phase of psychedelic imagery, the activation of subregions of the visual cortex will be from low level to high level areas, which is according to the subjective dynamics of the experience – i.e. from simple to complex. This was tested in 9 subjects that were scanned in the fMRI during the onset or “come-up” phase - i.e. 3 minutes post (1 min) infusion of 2mg psilocybin IV - which has a particularly fast onset. Results in this study revealed that during the onset phase the BOLD dynamics of regions within the ventral stream are organized by the hierarchy of regions. Overall, study 1 and 2 revealed that, with eyes closed, under LSD, communication patterns between visual cortex and the rest of the brain and within the visual cortex match the kind of processing known to occur during regular vision. This adds to a body of knowledge supporting the view that the visual cortex is particularly engaged under the influence of psychedelics, and by measuring patterns of connectivity, we were able to provide strong support for the view that abnormal activity in the visual cortex underlies psychedelic imagery.
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... The representation of complex hallucinations has been associated with higher-order visual regions [21][22][23] . However, in psychedelic visual hallucinations, complex percepts resembling figurative constructs often also incorporate geometric elements, suggesting that there may not be a binary distinction between simple and complex hallucinations, and that lower-level visual areas may be concurrently active with higher-level visual areas during complex imagery 24 . This could suggest that simple hallucinations arise when activity is strongest in lower-level areas, whereas complex hallucinations arise when this activity travels up the visual hierarchy, either alone or in conjunction with top-down interpretative influences 13,25,26 . ...
... It is also worth considering the relative uncertainty associated with the words used to describe the Ganzfeld condition (for instance shadows, faded, disappeared, slightly, sort). This may suggest that some percepts in Ganzfeld lack the clarity, spatial resolution, and vividness observed in the largely bottom-up driven flicker hallucinations 24,26,62,63 . ...
Hallucinatory experiences, defined as perception in the absence of external stimuli, can occur in both pathological and non-pathological states and can be broadly phenomenologically divided into those of a simple and a complex nature. Non-pathological visual hallucinations can be induced experimentally using a variety of stimulation conditions. To assess whether these techniques drive a shared underlying hallucinatory mechanism, despite these differences, we compared two methods: flicker and perceptual deprivation (Ganzfeld). Specifically, we measured the frequency and complexity of the hallucinations produced by these techniques. We utilised button press, retrospective drawing, interviews, and questionnaires to quantify hallucinatory experience in 20 participants. With both experimental techniques, we found that simple hallucinations were more common than complex hallucinations. We also found that on average, flicker was more effective than Ganzfeld at eliciting a higher number of hallucinations, though Ganzfeld hallucinations were longer than flicker hallucinations. There was no interaction between experimental condition and hallucination complexity, suggesting that the increased bottom-up visual input in flicker increased both simple and complex hallucinations similarly. A correlation was observed between the total proportional time spent hallucinating in flicker and Ganzfeld, which was replicated in a retrospective questionnaire measure of experienced intensity, suggesting a shared hallucinatory mechanism between the two methodologies. We attribute these findings to a shared low-level core hallucinatory mechanism, such as excitability of visual cortex, which is amplified in flicker compared to Ganzfeld due to heightened bottom-up input.
... Classic psychedelics are a family of drugs whose central mode of action is through the 2A receptor of the serotonergic system (Nichols, 2016). Their effect is known to be context-dependent Hartogsohn, 2017;Hartogsohn, 2020), and they are known to produce a myriad of intense experiences (Harner, 1973;Grof, 1975Grof, /2016Shanon, 2002), including so-called mystical-type and ego-dissolution experiences (Pahnke and Richards, 1966;Griffiths et al., 2008;Nour et al., 2016), emotional breakthrough, release or catharsis and psychological processing of traumatic events (Frederking, 1955;Riba et al., 2006;Gasser et al., 2014;Belser et al., 2017;Roseman et al., 2019), challenging high-anxiety experiences (Carbonaro et al., 2016), prophetic-type experiences (Strassman, 2014), visionary and hallucinatory experiences (Knauer and Maloney, 1913;Klüver, 1926;Reichel-Dolmatoff, 1975;Luna andAmaringo, 1991/1999;Shanon, 2002;Roseman, 2019), and experiences of social connection (Dolder et al., 2016;Pokorny et al., 2017;Apud, 2020b;Forstmann et al., 2020;Kettner et al., 2021). The context-dependent quality of psychedelics has led them to be referred as 'non-specific amplifiers' (Grof, 1975(Grof, / 2016)meaning they intensify whatever is in the vicinity of the experiencer, whether good or bad or intrinsically (e.g., in their own mind) or extrinsically located (i.e., in their immediate environment). ...
Psychedelics are used in many group contexts. However, most phenomenological research on psychedelics is focused on personal experiences. This paper presents a phenomenological investigation centered on intersubjective and intercultural relational processes, exploring how an intercultural context affects both the group and individual process. Through 31 in-depth interviews, ceremonies in which Palestinians and Israelis drink ayahuasca together have been investigated. The overarching question guiding this inquiry was how psychedelics might contribute to processes of peacebuilding, and in particular how an intercultural context, embedded in a protracted conflict, would affect the group’s psychedelic process in a relational sense. Analysis of the interviews was based on grounded theory. Three relational themes about multilocal participatory events which occurred during ayahuasca rituals have emerged from the interviews: 1) Unity-Based Connection – collective events in which a feeling of unity and ‘oneness’ is experienced, whereby participants related to each other based upon a sense of shared humanity, and other social identities seemed to dissolve (such as national and religious identities). 2) Recognition and Difference-Based Connection – events where a strong connection was made to the other culture. These events occurred through the expression of the other culture or religion through music or prayers, which resulted in feelings of awe and reverence 3) Conflict-related revelations – events where participants revisited personal or historical traumatic elements related to the conflict, usually through visions. These events were triggered by the presence of ‘the Other,’ and there was a political undertone in those personal visions. This inquiry has revealed that psychedelic ceremonies have the potential to contribute to peacebuilding. This can happen not just by ‘dissolution of identities,’ but also by providing a space in which shared spiritual experiences can emerge from intercultural and interfaith exchanges. Furthermore, in many cases, personal revelations were related to the larger political reality and the history of the conflict. Such processes can elucidate the relationship between personal psychological mental states and the larger sociopolitical context.
... In addition, intermediary and high-level association networks (the default, frontoparietal control, dorsal attention, and salience networks) all exhibited trends towards increased 'visualness' in the LSD state. While speculative, this pattern of increased cross-talk between visual regions and regions subserving abstract cognitive processing may relate to the vivification of eyes-closed imagery that is characteristic of the psychedelic experience (Carhart-Harris, Muthukumaraswamy, et al., 2016;Kraehenmann et al., 2017;Roseman, 2018). Consistent with this idea, we observed a significant relationship between the 'visualness' of clusters in the superior temporal gyrus and superior-medial somatosensory cortex and complex imagery in the LSD state. ...
LSD and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to pharmacological resting-state fMRI data to assess cortical organization in the LSD and psilocybin state. Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes: default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping confirmed that this was underpinned by increased unimodal-transmodal crosstalk. In addition, LSD-dependent principal gradient changes tracked changes in self-reported ego-dissolution. Results involving the second and third gradient, which respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to a pharmacological manipulation, specifically highlighting an important relationship between cortical organization and serotonergic modulation.
The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.
Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively. Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a “mystical-type experience” had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., “challenging experience” and “visual effects”, did not influence the change in well-being after the psychedelic experience. Having “clear intentions” for the experience was conducive to mystical-type experiences. Having a positive “set” as well as having the experience with intentions related to “recreation” were both found to decrease the likelihood of having a challenging experience. The baseline trait “absorption” and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed that baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.
Winkelman’s newest edition of Shamanism provides an extensive revision of Shamanism (2000) and extends our understanding of the evolutionary origins of humanity’s first spiritual, healing and consciousness traditions. Shamanism A Biopsychosocial Paradigm of Consciousness and Healing (2010) addresses: cross-cultural perspectives on the nature of shamanism; biological perspectives on alterations of consciousness; mechanisms of shamanistic healing; and the evolutionary origins of shamanism. It presents the shamanic paradigm as a biopsychosocial framework for explaining human evolution through group rituals that provided bases for enhanced group functioning.
The new subtitle emphasizes that what has been conventionally considered a spiritual practice has ancient biological, social and psychological roots. This book distinguishes itself by: 1) addressing shamanism in cross-cultural perspective; 2) explaining the biological roots of shamanism; and 3) providing biological and social evolutionary models of the development of shamanistic healing practices. These approaches illustrate why shamanism was central to ancient societies and provides healing in the modern world. Analysis of the relationship of shamanic ritual to primate rituals reveals the phylogenetic origins of shamanic ritual and illustrates why shamanism must be central to explanation of humanity’s religious impulses.
1. Provides a cross-cultural and biological perspective on the nature of shamanism
2. Presents a shamanic paradigm for interpretation of shamanism in the past
3. Develops biological models to explain shamanic universals
4. Illustrates the biological bases of shamanic alterations of consciousness and healing practices
5. Develops an evolutionary model of shamanic practices
6. Provides a general foundation for understanding the biological bases of religion
Endorsements:
“Winkelman’s Shamanism has replaced Mircea Eliade’s classic text as the most authoritative and innovative book on the topic. Winkelman demonstrates shamanism’s adaptive functions and why its study must be central to any comprehensive explanation of humanity’s origins.”
– Stanley Krippner, Professor of Psychology, Saybrook University
“The second edition of Winkelman’s Shamanism is a must read for any serious student of shamanism or the evolution of religious systems.”
– Charles D. Laughlin, co-author of Brain, Symbol, and Experience
“Shamanism breaks new ground in our understanding of the origins of religion, and the qualities that uniquely make us human. Essential reading for anyone interested in shamanism, human evolution, the origin of religion, and traditional healing practices.”
– David S. Whitley, author of Cave Paintings and the Human Spirit
“Shamanism explores how the development of shamanic rituals was a key factor in human evolution.”
– Paul Devereux, founding co-editor, Time & Mind – The Journal of Archaeology, Consciousness & Culture
Psychedelic drugs are making waves as modern trials support their therapeutic potential and various media continue to pique public interest. In this opinion piece, we draw attention to a long-recognised component of the psychedelic treatment model, namely ‘set’ and ‘setting’ – subsumed here under the umbrella term ‘context’. We highlight: (a) the pharmacological mechanisms of classic psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe render their effects exceptionally sensitive to context, (b) a study design for testing assumptions regarding positive interactions between psychedelics and context, and (c) new findings from our group regarding contextual determinants of the quality of a psychedelic experience and how acute experience predicts subsequent long-term mental health outcomes. We hope that this article can: (a) inform on good practice in psychedelic research, (b) provide a roadmap for optimising treatment models, and (c) help tackle unhelpful stigma still surrounding these compounds, while developing an evidence base for long-held assumptions about the critical importance of context in relation to psychedelic use that can help minimise harms and maximise potential benefits.
Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value.
Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest.
Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).
Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.
Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797
Sacred Knowledge is the first well-documented, sophisticated account of the effect of psychedelics on biological processes, human consciousness, and revelatory religious experiences. Based on nearly three decades of legal research with volunteers, William A. Richards argues that, if used responsibly and legally, psychedelics have the potential to assuage suffering and constructively affect the quality of human life. Richards’s analysis contributes to social and political debates over the responsible integration of psychedelic substances into modern society. His book serves as an invaluable resource for readers who, whether spontaneously or with the facilitation of psychedelics, have encountered meaningful, inspiring, or even disturbing states of consciousness and seek clarity about their experiences. Testing the limits of language and conceptual frameworks, Richards makes the most of experiential phenomena that stretch our conception of reality, advancing new frontiers in the study of belief, spiritual awakening, psychiatric treatment, and social well-being. His findings enrich humanities and scientific scholarship, expanding work in philosophy, anthropology, theology, and religious studies and bringing depth to research in mental health, psychotherapy, and psychopharmacology.
Hallucinations possess two main components: (i) a sensory content; (ii) a sense that the sensory content is real. Influential models of schizophrenic hallucination claim that both the sensory content and the sense of reality can be explained in terms of metacognitive dysfunction. This chapter assesses whether such a claim holds for schizophrenic and drug-induced hallucinations; it further attempts to determine the actual role of metacognition in hallucination and how this role is liable to vary across cultures. It is first argued that the notion of sense of reality is heterogeneous and should therefore be divided into distinct kinds. Next, some monitoring-based models of hallucination are presented, and it is shown that they fail to explain important aspects of hallucinations. It is subsequently suggested that the main mechanisms of serotoninergic hallucinogens are not metacognitive, whereas those of anticholinergic hallucinogens importantly tap into subpersonal metacognitive processes. Finally, after specific consideration of the use of ayahuasca across different Amazonian indigenous groups, it is proposed that the metacognitive properties of hallucinogenic experiences can be variously exploited or ignored depending on cultural expectations.
The entropic brain hypothesis proposes that within upper and lower limits, after which consciousness may be lost, the entropy of spontaneous brain activity indexes the informational richness of conscious states. Here the hypothesis is revisited four years on from its original publication. It is shown that the principle that the entropy of brain activity is elevated in the psychedelic state is increasingly well supported by separate and independent studies and analyses, and evidence for greater brain criticality under psychedelics is also highlighted. It is argued that heightened brain criticality enables the brain to be more sensitive to intrinsic and extrinsic perturbations which may translate as a heightened susceptibility to “set” and “setting”. This updated version of the original entropic brain hypothesis now offers more concrete information on specific measures of brain entropy and suggests new studies to scrutinise it further, as well as examine its utility for describing and informing the treatment of psychiatric and neurological conditions such as depression and disorders of consciousness.
This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.