Article

Seeing without self: Discovering new meaning with psychedelic-assisted psychotherapy

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

New research in psychedelic-assisted psychotherapy merits a reexamination of the neurobiology and phenomenology of psychedelic states. First person accounts of psychedelic-assisted psychotherapy are used to re-conceptualize the ego boundary as a defense mechanism which regulates the significance that objects hold for the self. Therapeutic action is attributed to ego dissolution, which enables subjects to see new significance in things. This process coincides neurobiologically with uncoupling certain midline cortical structures, and psychodynamically, with deactivating defense mechanisms which mitigate the threat of losing the loved object. It also enables the dreamlike imagery, symbols, and metaphor of the primary process, a regression to earlier ways of relating to objects, and feelings of love and connectivity. The process supports Freud's ideas about the oceanic mode of relating to the world existing alongside the narrower, mature ego feeling. The former is better suited for finding meaning in life, while the latter is better suited for survival. The noetic quality of the psychedelic state derives from an unconscious recognition that experiences without character defenses feel more genuine than others, and conform to earlier ways of feeling and thinking. The accessibility of the primary process makes psychedelic-assisted psychotherapy transformative, not just informative. An analogy is drawn to Fonagy's developmental model of mentalization. Absent the defensive, self-critical lens of a prior self-concept, psychedelic-assisted psychotherapy serves as an ideal paradigm for the transformative experience of seeing oneself through the eyes of another, leading to greater self-acceptance. Flight instructions for navigating this royal road to the unconscious are considered.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Psilocybin-induced mystical experiences induce personal and spiritual significance which account for long-term enhancements in openness, positive attitudes, and prosocial behaviors (Griffiths et al., 2018;Griffiths, Richards, McCann, & Jesse, 2006;MacLean, Johnson, & Griffiths, 2011), are related to increased alcohol and smoking abstinence (Bogenschutz et al., 2015;Johnson, Garcia-Romeu, & Griffiths, 2017) and reduced anxiety and depression in patients with life-threatening cancer Ross et al., 2016). Ego-dissolution might support an altered perspective on the self and increased self-acceptance (Fischman, 2019). A 'psychedelic peak experience', including egodissolution, transcendence of time and space, and meaningful insights, was suggested as an important mechanism in LSD-assisted psychotherapy (Gasser, Kirchner, & Passie, 2015). ...
... Beyond that, the correlations of aberrant salience with mystical experiences and ego-dissolution might point to common mechanisms for psychotic, therapeutic and psychedelic experiences. Specifically, LSD-induced aberrant salience might increase significance attribution and reduce ego boundaries and defense mechanisms, allowing for therapeutic changes in perspectives and attitudes (Fischman, 2019). Similarly, aberrant salience exerts a modulatory role within psychotic experiences related to cannabis use and self-concept clarity (Cicero, Docherty, Becker, Martin, & Kerns, 2015;O'Tuathaigh et al., 2020). ...
Article
Background For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. Methods In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 μg d -lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined. Results LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience. Conclusions The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.
... Psychedelics may function by dramatically reducing or shifting an individual's defense mechanisms (Fischman, 2019). This can be useful for understanding both a patient's distress during a psychedelic experience and their subsequent alleviation of symptoms. ...
Article
Full-text available
Psychedelic Harm Reduction and Integration (PHRI) is a transtheoretical and transdiagnostic clinical approach to working with patients who are using or considering using psychedelics in any context. The ongoing discussion of psychedelics in academic research and mainstream media, coupled with recent law enforcement deprioritization of psychedelics and compassionate use approvals for psychedelic-assisted therapy, make this model exceedingly timely. Given the prevalence of psychedelic use, the therapeutic potential of psychedelics, and the unique cultural and historical context in which psychedelics are placed, it is important that mental health providers have an understanding of the unique motivations, experiences, and needs of people who use them. PHRI incorporates elements of harm reduction psychotherapy and psychedelic-assisted psychotherapy, and can be applied in both brief and ongoing psychotherapy interactions. PHRI represents a shift away from assessment limited to untoward outcomes of psychedelic use and abstinence-based addiction treatment paradigms and toward a stance of compassionate, destigmatizing acceptance of patients' choices. Considerations for assessment, preparation, and working with difficult experiences are presented.
... An enhanced sense of meaning is perhaps the overriding hallmark of the psychedelic experience, even above mystical phenomena and visual alteration [49][50][51][52][53]. This is best exemplified by the "noetic quality" of psychedelic mystical experiences. ...
Article
Psychedelics have shown great promise in modern clinical trials for treating various psychiatric conditions. As a transdiagnostic treatment that exerts its effects through subjective experiences that leave enduring effects, it is akin to psychotherapy. To date, there has been insufficient discussion of how psychedelic therapy is similar to and different from conventional psychotherapy. In this article, we review the shared features of effective conventional psychotherapies and situate therapeutic psychedelic effects within those. We then discuss how psychedelic drug effects might amplify conventional psychotherapeutic processes—particularly via effects on meaning and relationship—as well as features that make psychedelic treatment unique. Taking into account shared features of conventional psychotherapies and unique psychedelic drug effects, we create a framework for understanding why psychedelics are likely to be effective with very diverse types of psychotherapies. We also review the formal psychotherapies that have been adjunctively included in modern psychedelic trials and extend the understanding of psychedelics as psychotherapy towards implications for clinical ethics and trial design. We aim to provide some common conceptual vocabulary that can be used to frame therapeutic psychedelic effects beyond the confines of any one specific modality.
Article
Full-text available
Participants in MDMA- and psychedelic-assisted psychotherapy often emerge from these treatments with new beliefs about themselves and the world. Studies have linked changed beliefs with mystical experiences reported by some participants during drug sessions. While there has been some debate about the epistemic value of drug-induced mystical experiences, and about the need for consent to treatments that may alter metaphysical beliefs, less attention has been given to the sense of authenticity that attends these experiences. In this paper, I consider the intersubjective context in which these changed beliefs arise. I suggest that the sense of authenticity people experience with MDMA- and psychedelic-assisted psychotherapy derives from a simultaneous feeling of knowing and being known. The medications used in these treatments reduce the defensive barriers which ordinarily prevent powerful feelings from being intersubjectively shared, allowing the subject to experience knowing and being known with the therapist and/or internalized or imagined others. In explaining this thesis, I discuss Ratcliffe's “existential feeling;” ipseity in incipient psychosis and psychedelic states; Winnicott's notions of the True Self, omnipotence, creativity, and transitional phenomena; implicit relational knowing and moments of meeting; infant-mother dyad research; predictive processing and the relaxed beliefs model of psychedelic action; the role of the “partner in thought” in knowing and feeling known. I propose that a “transitional space” model of MDMA- and psychedelic-assisted psychotherapy is well-suited for working through “not-me” or dissociated experience
Article
Full-text available
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.
Article
In this paper I offer an overview of the possible links between psychoanalytical metapsychology and contemporary work in neuroscience concerning entropy and the free energy principle. After briefly describing the theory of living systems put forward by the neuroscientist Karl Friston based on the notion of entropy, we sum up the use of the notion of free energy by Friston and Freud. I then analyze how these notions improve the intelligibility of psychic functioning and can be associated with several psychoanalytical concepts, in particular the death drive. I approach from the same perspective the regulation of free energy associated with psychic envelopes and early intersubjectivity. It thus appears that the psychic apparatus can be considered at its different levels, from the most primary to the most secondary, as having the essential function of reducing entropy and free energy. Various forms of "failure" of this process of linking, regulation and transformation of energy within the psychic apparatus could be considered as the origin of different psychopathological manifestations as suggested in the last part of this paper.
Article
Résumé Objectif Cet article propose une revue de littérature concernant les psychédéliques dits classiques (LSD, psilocybine, DMT et mescaline) et, plus précisément, leur utilisation en psychothérapie dans le champ de la dépression, du point de vue des processus de symbolisation. Méthode Après quelques éléments introductifs portant sur la dépression, nous décrivons les principales caractéristiques des psychothérapies assistées par psychédélique et les résultats des essais cliniques modernes. Nous en présentons ensuite la phénoménologie et en proposons un éclairage théorique au croisement des neurosciences et de la psychanalyse, avant de conclure sur les perspectives ouvertes par cette thérapie. Résultats Les résultats déjà obtenus suggèrent qu’une seule dose, prise dans un environnement étayant, peut être suffisante pour produire des effets thérapeutiques significatifs et objectivables dès la prise de psychédéliques et au moins six mois après celle-ci. La réponse clinique dépend de l’intensité phénoménologique initiale de l’expérience et de la capacité du sujet à laisser advenir des reviviscences traumatiques. Elle dépend également de la présence et de l’intensité de vécus de nature mystique caractérisés par un sentiment de dissolution du moi et d’unité avec le monde. Discussion La thérapie assistée par psychédéliques semble favoriser l’émergence des processus primaires et la levée des mécanismes de défense. Les psychédéliques catalyseraient ainsi la relance des processus de symbolisation, favorisant notamment l’intégration de certains conflits psychiques ainsi que le remaniement de relations d’objets pathogènes. Sur le plan neurobiologique, ces processus seraient sous-tendus par une diminution de l’activité du réseau du mode par défaut – parfois considéré comme lié à certaines fonctions du Moi – associée à une dimension entropique du fonctionnement cérébral. Ces différents éléments participeront d’une diminution de la symptomatologie dépressive, en particulier des ruminations. Ces effets thérapeutiques nécessitent néanmoins un cadre clinique particulièrement contenant et un positionnement clinique plus engagé qu’à l’accoutumée afin d’accompagner dans les meilleures conditions ces potentiels effets de transformation psychique. Conclusions Les études déjà menées sur cette thématique soulignent le caractère très prometteur des psychédéliques dans la prise en charge de la dépression et de ses formes résistantes. Ces substances semblent opérer comme un catalyseur des processus de symbolisation qui nécessite néanmoins, pour se déployer pleinement, un accompagnement psychothérapique plus global à la croisée de la psychiatrie, la psychologie clinique, des neurosciences et de la psychanalyse.
Article
The recent renaissance in research on psychedelic-assisted psychotherapy is showing great promise for the treatment of many psychiatric conditions. Interestingly, therapeutic outcomes for patients undergoing these treatments are predicted by the occurrence of a mystical experience-an experience characterised in part by a sense of profound meaning. This has led to hypotheses that psychedelic-assisted psychotherapy is therapeutic because it enhances perception of meaning, and consequently leads to a meaning response (a therapeutic mechanism that has been well described in the philosophical literature on the placebo effect). The putative mechanism of action of psychedelics as meaning enhancers raises normative ethical questions as to whether it can be justified to pharmacologically increase the perception of meaning in order to heal patients. Using the perspectives of hedonistic moral theories, this paper argues that if psychedelics operate as meaning enhancers, psychedelic-assisted psychotherapy can be ethically justified. An anti-hedonistic objection is presented by applying Robert Nozick's Experience Machine thought experiment to the case of psychedelic-assisted psychotherapy. However, it is argued that this objection falls short for two reasons. First, even if pleasure and pain are not the only consequences which have moral value they are not morally irrelevant, therefore, therapeutic meaning enhancement can still be justified in cases of extreme suffering. Second, it is possible that psychedelic states of consciousness do not represent a false reality, hence their therapeutic meaning enhancement is not problematic according to Nozick's standards.
Article
Full-text available
This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that-via their entropic effect on spontaneous cortical activity-psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. SIGNIFICANCE STATEMENT: Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of how psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, hierarchical predictive coding, with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
Article
Full-text available
From the beginning of therapeutic research with psychedelics, music listening has been consistently used as a method to guide or support therapeutic experiences during the acute effects of psychedelic drugs. Recent findings point to the potential of music to support meaning-making, emotionality, and mental imagery after the administration of psychedelics, and suggest that music plays an important role in facilitating positive clinical outcomes of psychedelic therapy. This review explores the history of, contemporary research on, and future directions regarding the use of music in psychedelic research and therapy, and argues for more detailed and rigorous investigation of the contribution of music to the treatment of psychiatric disorders within the novel framework of psychedelic therapy.
Article
Full-text available
Background: Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. Aims: The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Methods: Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. Results: Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. Conclusions: The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.
Article
Full-text available
A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants’ personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.
Article
Full-text available
The article The hidden therapist: evidence for a central role of music in psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris, was originally published electronically on the publisher's internet portal.
Article
Full-text available
Past research has demonstrated to the ability of psychedelics to enhance suggestibility, and pointed to their ability to amplify perception of meaning. This paper examines the existing evidence for the meaning-enhancing properties of psychedelics, and argues that the tendency of these agents to enhance the perception of significance offers valuable clues to explaining their reported ability to stimulate a variety of therapeutic processes, enhance creativity, and instigate mystical-type experiences. Building upon previous research, which suggested the potential role of psychedelic meaning-enhancement in enhancing placebo response, the paper explores the mechanisms by which the meaning-amplifying properties of psychedelics might also play a role in enhancing creativity, as well as in effecting mystical-type experiences. The wider social and public-health implications of this hypothesis are discussed, and suggestions are made as to the various ways in which scientific understanding of the meaning-enhancing properties of psychedelics might be advanced and utilized.
Article
Full-text available
How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.
Article
Full-text available
Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking – an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness.
Article
Full-text available
RationaleLysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality. Methods We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI). ResultsOn the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found. Conclusions In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects. Trial registrationRegistration identification number: NCT01878942.
Article
Full-text available
Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.
Article
Full-text available
Users of psychedelic drugs often report that their sense of being a self or ‘I’ distinct from the rest of the world has diminished or altogether dissolved. Neuroscientific study of such ‘ego dissolution’ experiences offers a window onto the nature of self-awareness. We argue that ego dissolution is best explained by an account that explains self-awareness as resulting from the integrated functioning of hierarchical predictive models which posit the existence of a stable and unchanging entity to which representations are bound. Combining recent work on the ‘integrative self' and the phenomenon of self-binding with predictive processing principles yields an explanation of ego dissolution according to which self-representation is a useful Cartesian fiction: an ultimately false representation of a simple and enduring substance to which attributes are bound which serves to integrate and unify cognitive processing across levels and domains. The self-model is not a mere narrative posit, as some have suggested; it has a more robust and ubiquitous cognitive function than that. But this does not mean, as others have claimed, that the self-model has the right attributes to qualify as a self. It performs some of the right kinds of functions, but it is not the right kind of entity. Ego dissolution experiences reveal that the self-model plays an important binding function in cognitive processing, but the self does not exist.
Article
Full-text available
There is converging evidence that high doses of hallucinogenic drugs can produce significant alterations of self-experience, described as the dissolution of the sense of self and the loss of boundaries between self and world. This article discusses the relevance of this phenomenon, known as “drug-induced ego dissolution (DIED)”, for cognitive neuroscience, psychology and philosophy of mind. Data from self-report questionnaires suggest that three neuropharmacological classes of drugs can induce ego dissolution: classical psychedelics, dissociative anesthetics and agonists of the kappa opioid receptor (KOR). While these substances act on different neurotransmitter receptors, they all produce strong subjective effects that can be compared to the symptoms of acute psychosis, including ego dissolution. It has been suggested that neuroimaging of DIED can indirectly shed light on the neural correlates of the self. While this line of inquiry is promising, its results must be interpreted with caution. First, neural correlates of ego dissolution might reveal the necessary neurophysiological conditions for the maintenance of the sense of self, but it is more doubtful that this method can reveal its minimally sufficient conditions. Second, it is necessary to define the relevant notion of self at play in the phenomenon of DIED. This article suggests that DIED consists in the disruption of subpersonal processes underlying the “minimal” or “embodied” self, i.e., the basic experience of being a self rooted in multimodal integration of self-related stimuli. This hypothesis is consistent with Bayesian models of phenomenal selfhood, according to which the subjective structure of conscious experience ultimately results from the optimization of predictions in perception and action. Finally, it is argued that DIED is also of particular interest for philosophy of mind. On the one hand, it challenges theories according to which consciousness always involves self-awareness. On the other hand, it suggests that ordinary conscious experience might involve a minimal kind of self-awareness rooted in multisensory processing, which is what appears to fade away during DIED.
Article
Full-text available
The psychological mechanisms of action involved in psilocybin-assisted psychotherapy are not yet well understood. Despite a resurgence of quantitative research regarding psilocybin, the current study is the first qualitative study of participant experiences in psilocybin-assisted psychotherapy. Semistructured interviews were carried out with 13 adult participants aged 22 to 69 years (M = 50 years) with clinically elevated anxiety associated with a cancer diagnosis. Participants received a moderate dose of psilocybin and adjunctive psychotherapy with an emphasis on the process of meaning-making. Verbatim transcribed interviews were analyzed by a five-member research team using interpretative phenomenological analysis. General themes found in all or nearly all transcripts included relational embeddedness, emotional range, the role of music as conveyor of experience, meaningful visual phenomena, wisdom lessons, revised life priorities, and a desire to repeat the psilocybin experience. Typical themes found in the majority of transcripts included the following: exalted feelings of joy, bliss, and love; embodiment; ineffability; alterations to identity; a movement from feelings of separateness to interconnectedness; experiences of transient psychological distress; the appearance of loved ones as guiding spirits; and sharing the experience with loved ones posttreatment. Variant themes found in a minority of participant transcripts include lasting changes to sense of identity, synesthesia experiences, catharsis of powerful emotion, improved relationships after treatment, surrender or “letting go,” forgiveness, and a continued struggle to integrate experience. The findings support the conclusion that psilocybin-assisted psychotherapy may provide an effective treatment for psychological distress in cancer patients. Implications for theory and treatment are discussed.
Article
Full-text available
RationaleAccumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming. Objectives This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire. ResultsLSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin. ConclusionsLSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.
Article
Full-text available
Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595
Article
Full-text available
Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial registration: ClinicalTrials.gov Identifier: NCT00957359.
Article
Full-text available
Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment.
Article
Full-text available
Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.
Article
Full-text available
Viewing the Earth from space has often prompted astronauts to report overwhelming emotion and feelings of identification with humankind and the planet as a whole. In this article, we explore this experience, known as the “overview effect.” We examine astronaut accounts of the overview effect and suggest existing psychological constructs, such as awe and self-transcendent experience, that might contribute to a psychological understanding of this experience. We argue that the overview effect suggests directions for future research on altered states of consciousness in new contexts, with potential implications for better understanding well-being in isolated, confined, extreme (ICE) environments such as space flight.
Article
Full-text available
The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest, but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified ‘core-self’ DMN regions — in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule — using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity, and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes, and extend our understanding of their functionally specialized roles.
Article
Full-text available
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybinassisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network. © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Article
Full-text available
While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the Experience Sampling Method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with First-Episode Psychosis (FEP), 46 individuals with an At-Risk Mental State (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all three groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ2=6.3, p=0.044), activities (χ2=6.7, p=0.036), and areas (χ2=9.4, p=0.009) and enhanced threat anticipation (χ2=9.3, p=0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ2=5.7, p=0.058) and aberrantly salient experiences (χ2=12.3, p=0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder.
Article
Full-text available
We propose a new account of how self-reference affects information processing. We report evidence that self-reference affects the binding of memory to source, the integration of parts into perceptual wholes, and the ability to switch from a prior association to new associations. Self-reference also influences the integration of different stages of processing, linking attention to decision making, and affects the coupling between brain regions mediating self-representation and attention to the environment. Taken together, the data suggest that self-reference acts as a form of 'integrative glue' which can either enhance or disrupt performance, depending on the task context. We discuss the implications for understanding the self, and future directions for research.
Article
Full-text available
There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.
Article
Full-text available
During the last years, considerable progress has been made toward understanding the neuronal basis of consciousness by using sophisticated behavioral tasks, brain-imaging techniques, and various psychoactive drugs. Nevertheless, the neuronal mechanisms underlying some of the most intriguing states of consciousness, including spiritual experiences, remain unknown. To elucidate state of consciousness-related neuronal mechanisms, human subjects were given psilocybin, a naturally occurring serotonergic agonist and hallucinogen that has been used for centuries to induce spiritual experiences in religious and medical rituals. In this double-blind, placebo-controlled study, 50 healthy human volunteers received a moderate dose of psilocybin, while high-density electroencephalogram (EEG) recordings were taken during eyes-open and eyes-closed resting states. The current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions were computed and correlated with psilocybin-induced altered states of consciousness. Psilocybin decreased the current source density of neuronal oscillations at 1.5-20 Hz within a neural network comprising the anterior and posterior cingulate cortices and the parahippocampal regions. Most intriguingly, the intensity levels of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, the parahippocampus, and the lateral orbitofrontal area. These results provide systematic evidence for the direct association of a specific spatiotemporal neuronal mechanism with spiritual experiences and enhanced insight into life and existence. The identified mechanism may constitute a pathway for modulating mental health, as spiritual experiences can promote sustained well-being and psychological resilience.
Chapter
Full-text available
This chapter reviews the potential of a treatment approach that uses psilocybin, a novel psychoactive drug, to ameliorate the psychospiritual distress and demoralization that often accompany a life-threatening cancer diagnosis. The focus of cutting-edge research beginning in the 1950s, the investigation of classic hallucinogens had a major impact on the evolving field of psychiatry, contributing to early discoveries of basic neurotransmitter systems and to significant developments in clinical psychopharmacology. While published reports of therapeutic breakthroughs with difficult-to-treat and refractory patient populations were initially met with mainstream professional enthusiasm, by the late 1960s and early 1970s the growing association of hallucinogens with widespread indiscriminate use led to the temporary abandonment of this promising psychiatric treatment model. After a hiatus lasting several decades, however, regulatory and scientific support has grown for the resumption of clinical research investigations exploring the safety and efficacy of a treatment model utilizing the classic hallucinogen, psilocybin, in a subject population that had previously demonstrated positive therapeutic response, patients with existential anxiety due to a life-threatening cancer diagnosis.
Article
Full-text available
The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.
Article
The decade of the 1950s is well known among historians of psychiatry for the unprecedented shift toward psychopharmacological solutions to mental health problems. More psychiatric medications were introduced than ever before or since (Healy, 2002). While psychiatric researchers later credited these drugs, in part, for controlling psychotic, depressive, and anxious symptoms—and subsequently for emptying decaying psychiatric institutions throughout the Western world—psychiatrists also produced a number of other theories that relied on a more delicate and nuanced blending of psychotherapy and psychopharmacology. Canadian-based researchers were at the forefront of experiments combining mescaline, LSD, and psychoactive substances later described as “psychedelics.” From a relatively isolated setting on the Canadian prairies, in one of the most notorious mental hospitals in North America, this blending of traditions generated a unique approach. A close look at the correspondence between the psychiatrist Humphry Osmond and his friend, the writer Aldous Huxley, who shared interests in psychoactive substances and their effects on perception, and the stimulation of empathy, gives us an opportunity to explore how they developed their psychedelic approach to therapy in the 1950s. The combination of working in an isolated hospital, far from the main research powers in North America, produced a sense of regional incubation and required Osmond to look for collaborators well beyond his own field of psychiatry.
Book
‘The biological birth of the human infant and the psychological birth of the individual are not coincident in time. The former is a dramatic, observable, and well-circumscribed event; the latter a slowly unfolding intra psychic process.‘Thus begins this highly acclaimed book in which the author and her collaborators break new ground in developmental psychology and present the first complete theoretical statement of the author’s observations on the normal separation-individuation process. Separation and individuation are presented in this major work as two complementary developments. Separation is described as the child’s emergence from a symbiotic fusion with the mother, while individuation consists of those achievements making the child’s assumption of his own individual characteristics. Each of the sub-phases of separation-individuation is described in detail, supported by a wealth of clinical observations which trace the tasks confronting the infant and his mother as he progresses towards achieving his own individuality.
Article
In the 20th century we thought the brain extracted knowledge from sensations. The 21st century witnessed a ‘strange inversion’, in which the brain became an organ of inference, actively constructing explanations for what’s going on ‘out there’, beyond its sensory epithelia. One paper played a key role in this paradigm shift.
Article
Five-Factor Theory provides a broad but largely blank template for causal personality research. Within Five-Factor Theory, there are three major categories of questions: (1) how do biological structures and functions lead to trait levels? (2) how do traits and the environment give rise to acquired psychological institutions? and (3) how do personality characteristics interact with specific situations to determine behaviours and reactions? Both practical and ethical issues complicate the search for the causes of trait change. Causal explanations of the development of characteristic adaptations are likely to be incomplete, because there are many different ways in which the same adaptation may be acquired. Studies of the determinants of behaviour are usually left to social, educational, or clinical psychologists—although personality psychologists may make distinctive contributions by emphasizing the role of the individual in selecting and creating situations. A causal understanding of the functioning of the personality system is possible through the integration of many lines of evidence, but it is likely to take a very long time. In the meanwhile, personality psychologists may fruitfully pursue the identification of practical causes by which individuals with a given set of traits can optimize their adaptation. Copyright © 2018 European Association of Personality Psychology
Article
Objective: To identify patients’ perceptions of the value of psilocybin as a treatment for depression. Method: Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments. Results: Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance. Conclusions: These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.
Article
One of the lawlike regularities of psychological science is that of developmental progression-an increase in sensorimotor, cognitive, and social functioning from childhood to adulthood. Here, we report a rare violation of this law, a developmental reversal in attention. In Experiment 1, 4- to 5-year-olds ( n = 34) and adults ( n = 35) performed a change-detection task that included externally cued and uncued shapes. Whereas the adults outperformed the children on the cued shapes, the children outperformed the adults on the uncued shapes. In Experiment 2, the same participants completed a visual search task, and their memory for search-relevant and search-irrelevant information was tested. The young children outperformed the adults with respect to search-irrelevant features. This demonstration of a paradoxical property of early attention deepens current understanding of the development of attention. It also has implications for understanding early learning and cognitive development more broadly.
Article
A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.
Article
Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.
Article
Presented at a conference titled “Psychedelic Science 2013,” highlighting the resumption of investigations with psychedelic substances (i.e., psilocybin, DMT, LSD, MMDA, etc.) in the United States and Europe after a dormant period of more than two decades, the author presents insights and perspectives gleaned from his 25 years of clinical research experience. After acknowledging the vastness and potential significance of this research frontier, the article focuses on the “cartography of inner space”; the unique therapeutic potential of transcendental states of consciousness; the entelechy of the interpersonally grounded psyche; the importance of integration in drug-free therapy sessions; the roles of expectation, religious education and faith; the role of music; and future research directions.
Article
Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.
Article
This paper presents an argument for research into the means of altering individual attitudes, values, and communication abilities in the direction of increased social empathy, which, in turn, would produce a more favorable environment for resolving differences and facilitate peaceful negotiations between individuals and nations. It is proposed that prior research with the drug, d-lysergic acid diethylamide (LSD), shows sufficient promise in producing relatively long-lasting changes in the above areas to merit further research. Furthermore, the use of LSD has been demonstrated to be quite safe under supervisory conditions, i.e., the guided “trip.” LSD is also nontoxic and non-addictive. A brief history of psychedelic drugs is provided along with a description of their psychological effects. Some possible modes of action are discussed. LSD and other psychedelics are seen as possible means of tapping mental resources which are not ordinarily available, but which may be of great value to the individual and ultimately to the society. No attempt is made in this paper to discuss how the use of a drug such as LSD might be implemented in international peace negotiations. It is contended, however, that results of previous experiments demonstrate increased tolerance for opposing viewpoints, increased understanding, and increased social empathy. It would be very important, based on the above findings, to explore the potential psychedelic drugs may have in reducing the threat of nuclear war. © 1985, Florida State University College of Criminology and Criminal Justice. All rights reserved.
Article
Ego-disturbances have been a topic in schizophrenia research since the earliest clinical descriptions of the disorder. Manifesting as a feeling that one's "self," "ego," or "I" is disintegrating or that the border between one's self and the external world is dissolving, "ego-disintegration" or "dissolution" is also an important feature of the psychedelic experience, such as is produced by psilocybin (a compound found in "magic mushrooms"). Fifteen healthy subjects took part in this placebo-controlled study. Twelve-minute functional MRI scans were acquired on two occasions: subjects received an intravenous infusion of saline on one occasion (placebo) and 2 mg psilocybin on the other. Twenty-two visual analogue scale ratings were completed soon after scanning and the first principal component of these, dominated by items referring to "ego-dissolution", was used as a primary measure of interest in subsequent analyses. Employing methods of connectivity analysis and graph theory, an association was found between psilocybin-induced ego-dissolution and decreased functional connectivity between the medial temporal lobe and high-level cortical regions. Ego-dissolution was also associated with a "disintegration" of the salience network and reduced interhemispheric communication. Addressing baseline brain dynamics as a predictor of drug-response, individuals with lower diversity of executive network nodes were more likely to experience ego-dissolution under psilocybin. These results implicate MTL-cortical decoupling, decreased salience network integrity, and reduced inter-hemispheric communication in psilocybin-induced ego disturbance and suggest that the maintenance of "self"or "ego," as a perceptual phenomenon, may rest on the normal functioning of these systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Article
The history of research with psychedelic drugs has produced a variety of methods for their use and conflicting claims about results. First came the wave of excitement among experimentalists in the 1950s when it was claimed that lysergic acid diethylamide (LSD) could produce a model psychosis which might be useful in understanding schizophrenia. While this promise was fading, enthusiastic reports about the possibility of LSD as an aid to psychotherapy in the treatment of alcoholism and other psychiatric disorders appeared. All these approaches were represented in 1959 at the first international conference devoted entirely to LSD.1 Since then, there have been at least five more published proceedings of such conferences on various aspects of psychedelic drugs.2-6 The most recent conference on various means of producing states of consciousness was sponsored by the Menninger Foundation and the American Association of Humanistic Psychology on April 7 to 11, 1969, in
Article
Preliminary results of a study of psychedelic therapy are reported. Patients receive LSD and mescaline in a supportive setting following intensive preparation. Subjective questionnaire data from 113 patients reveal a high frequency of claimed benefit, low frequency of negative reaction, and a high relation between claimed benefit and reported “greater awareness of ultimate reality” through the LSD experience. Clinical data on 74 cases including blind ratings of MMPI profiles substantiate the claimed improvement rate. Cases in each of five improvement categories are summarized and before, 2-mo.-after, and 6-mo.-after MMPI data are included. Total improvement rate is above 80%. Follow-ups range from 6 mo. to 2 yr.