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Abstract

Research into the basic effects and therapeutic applications of psychedelic drugs has grown considerably in recent years. Yet, pressing questions remain regarding the substances’ lasting effects. Although individual studies have begun monitoring sustained changes, no study to-date has synthesized this information. Therefore, this systematic review aims to fill this important gap in the literature by synthesizing results from 34 contemporary experimental studies which included classic psychedelics, human subjects, and follow-up latencies of at least two weeks. The bulk of this work was published in the last five years, with psilocybin being the most frequently administered drug. Enduring changes in personality/attitudes, depression, spirituality, anxiety, wellbeing, substance misuse, meditative practices, and mindfulness were documented. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were related to these long-term changes in psychological functioning. Finally, with proper screening, preparation, supervision, and integration, limited aversive side effects were noted by study participants. Future researchers should focus on including larger and more diverse samples, lengthier longitudinal designs, stronger control conditions, and standardized dosages.

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... In modern studies, considering dosage and setting as well as excluding those with predispositions toward psychotic conditions has resulted in a high degree of safety and generally positive outcomes. 39 However, if the medicalization of psychedelic drugs is to continue its expansion, it is imperative that researchers and clinicians develop more specific criteria to predict the valence of acute effects for any one given individual. Moreover, improved screening methods for psychedelic treatment should reduce adverse reactions and time spent on ineffective treatments. ...
... The researchers first found that baseline measures of conscientiousness were strongly correlated with acute changes in suggestibility (r = 0.89). 51 Given that suggestibility has been argued to be one factor underlying the drugs' transdiagnostic benefits, 39 baseline measures of conscientiousness could be an important predictor to include when screening participants. The authors also found that predrug mental imagery ability was positively correlated with acute increases in vividness of mental imagery (r = 0.72). ...
... 66 Critically, across several studies and research groups, absorption was a replicable predictor of mystical-type experiences. 40,46,47,54 Given the role of mystical-type experiences in facilitating therapeutic changes with psychedelics, 39 it appears the trait of absorption may be an important variable to consider when evaluating if psychedelics are likely to be an effective treatment for an individual. Moreover, absorption has been shown to be related to 5-HT2AR binding potential, 67 which is consistent with recent research indicating that 5-HT2AR binding potential may be a biomarker for predicting psychedelic drug effects. ...
Article
Psychedelic drugs are increasingly being incorporated into therapeutic contexts for the purposes of promoting mental health. Yet, they can also induce adverse reactions in some individuals, and it is difficult to predict pre-treatment who is likely to experience positive or adverse acute effects. Although consideration of setting, dosage, and excluding individuals with psychotic predispositions has thus far led to a high degree of safety, it is imperative researchers develop a more nuanced understanding of how to predict individual reactions. To this end, the current systematic review coalesced the results of 14 studies that included baseline states or traits predictive of the acute effects of psychedelics. Individuals high in the traits of absorption, openness, and acceptance as well as a state of surrender were more likely to have positive and mystical-type experiences, whereas those low in openness and surrender, or in preoccupied, apprehensive, or confused psychological states were more likely to experience acute adverse reactions. Participant sex was not a robust predictor of drug effects, but 5-HT2AR binding potential, executive network node diversity, and rACC volume may be potential baseline biomarkers related to acute reactions. Lastly, increased age and experience with psychedelics were individual differences related to generally less intense effects, indicating users may become slightly less sensitive to the effects of the drugs after repeated usage. Although future well-powered, placebo-controlled trials directly comparing the relative importance of these predictors is needed, this review synthesizes the field's current understanding of how to predict acute reactions to psychedelic drugs.
... The purpose of this essay is to draw attention to emerging research on psychedelic-assisted therapy as a potential mechanism to foster long-term behavioral change and aid in the desistance process (Aday et al., 2020;Griffiths et al., 2008Griffiths et al., , 2011MacLean et al., 2011). In doing so, the following sections (1) define psychedelic-assisted therapy, (2) introduce criminologists to historical and contemporary research on psychedelic therapy as means to induce positive behavioral change, (3) highlight the relevance of psychedelic-assisted therapy to existing criminological theories of desistance, namely those pointing to cognitive shifts and identity transformation as essential to the desistance process, and (4) document the potential challenges and ethical issues with the implementation of psychedelic-assisted therapy among criminal justice populations. ...
... The history of psychedelic drug use among human populations for healing purposes dates back hundreds of years (Aday et al., 2020;Jay, 2019). Contemporary psychedelic-assisted therapy refers to the clinical implementation of psychedelic substances in conjunction with a psychotherapeutic intervention. ...
... The mechanism behind these benefits for dramatic behavioral change lies in evidence suggesting that psychedelicassisted therapy can engender profound experiences which facilitate long-lasting positive changes in attitudes, mood, altruism, behavior, psychological functioning, life satisfaction, and key personality domains such as openness (Griffiths et al., 2008MacLean et al., 2011). Moreover, findings from studies have also demonstrated that the positive and long-lasting changes often result from just a single dose of a psychedelic substance (Aday et al., 2020;Griffiths et al., 2006;Krebs & Johansen, 2012;MacLean et al., 2011), suggesting that such interventions may be more efficient, low cost, and long-lasting than many existing criminal justice interventions. ...
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Before conducting research in an Indigenous community, a researcher, especially a non-Indigenous researcher, must recognize and acknowledge not only the historical impact research has had on Indigenous communities but the current impacts that arise when research is conducted in Indigenous communities. Specifically, one must consider settler colonialism and its continuing impact on Indigenous communities today. Professor of Indigenous Education Linda Tuhiwai Smith (2012) states: “The word itself, ‘research’, is probably one of the dirtiest words in the Indigenous world’s vocabulary”. Smith continues by linking research and Western imperialism and colonialism together, with research being a tool for imperialism and colonialism. Therefore, it is critical to identify how research and its processes have been used to justify the dehumanization of Indigenous people in order to gain and maintain power over Indigenous communities. Researchers must ensure that their research does not perpetuate unequal power dynamics and is based on a collective process. Suggestions for best practices for working with Indigenous people/communities are presented below.
... 17,47 It should be noted, however, that there are several limitations to much of the current research, including unstandardized dosages, homogenous samples, expectancy effects, and small sample sizes. 23 In addition, while psychedelics are non-toxic (i.e., do not damage mammalian organ systems) 48 and have low potential for abuse, 49 the drugs are not risk-free as they can lead to psychologically challenging experiences for some individuals. 50 Even with robust therapeutic support, up to a third of participants experience transient fear or panic at some point during high-dose sessions. ...
... Next, it may be useful to directly compare the effect sizes between research integrating psychedelics or VR into therapy (Table 2). Aday et al. 23 compiled the effect sizes for long-term changes in depression after psychedelic-assisted psychotherapy, and found that η p 2 ranged from 0.32 to 0.70, Hedges' g from 0.7 to 3.2, and Cohen's d from 0.82 to 2.3. Li and colleagues reviewed the research on VR therapy for depression and found an average Cohen's d of 0.67, 59 but this average was derived from just two studies. ...
Article
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Psychedelic drugs and virtual reality (VR) each have the capacity to disrupt the rigidity and limitations of typical conscious experience. This article delineates the parallels among psychedelic and VR states as well as their potential synergistic applications in clinical and recreational settings. Findings indicate that, individually, psychedelics and VR are used in analogous ways to alter sensory experience and evoke awe. They are also both used in tandem with traditional therapies to treat a variety of mood disorders; their shared capacity to transiently alter perspective and disrupt rigid patterns of mental experience may underly their analogous and transdiagnostic therapeutic uses. In terms of their combined applications, a number of recreational users currently utilize psychedelics and VR together to enhance their experience. We propose that VR may be a useful tool for preparing hallucinogen-naïve participants in clinical trials for the sensory distortions experienced in psychedelic states. Given the critical role of “setting” in psychedelic treatment outcomes, we also detail how VR could be used to optimize the environment in psychedelic sessions. Finally, we provide considerations for future studies and detail how advancements in psychedelic and VR research can inform one another. Collectively, this article outlines a number of connections between psychedelics and VR, and, more broadly, is representative of growing scientific interest into the interactions among technology, psychopharmacology, and mental health.
... Research continues to positively demonstrate the potential of entheogens and psychedelics for human health and emotional wellbeing (Gandy, 2019;Griffiths et al., 2016;Ross et al., 2016). Furthermore, physiological risks associated with traditional entheogens currently used in Canada (Psilocybin, Ayahuasca, Peyote) appear to be minimal, with the exception of use with contraindicated medications, as they possess few side effects, have low toxicity, and are nonaddictive (e.g., Aday et al., 2020;Johansen & Krebs, 2015). Nevertheless, these substances can profoundly alter mood and perceptions. ...
... Residual adverse effects can include lasting painful emotional experiences (so-called "bad trips," or painful, disorienting "flashbacks"), depression, and even psychotic states with delusions and hallucinations, although some studies contradict these assertions (Aday et al., 2020;Johnson et al., 2008;Matefy, 1974). These experiences can be understood as arising from internal psychospiritual experiences, and due to a lack of skilled and experienced guidance or supervision, these experiences remain misunderstood, unresolved, and unintegrated. ...
Article
After decades of prohibition, scientific and academic inquiry into the psychedelic sciences has been reignited in the West. Alongside research, clinicians are being permitted to study the effects of psychedelic substances in humans, and the door has been opened to deliver psychedelic-assisted therapies for mental health needs. However, despite excitement for the professional use of psychedelics, there are few, if any, overarching principles regulating such studies and treatment approaches in Canada. To this end, experts in religious studies, psychiatry, clinical psychology, palliative care, anthropology, ethics, and legal studies assembled to assess the developing situation and form recommendations, as an initial step in laying the groundwork for therapeutic, spiritual, and research involvement/activities with psychedelics. This paper reviews the historical context of entheogens in indigenous traditions; a current view of the field in Canada; potential risks associated with psychedelic use; recommendations regarding ethical guidelines and education and training; and criteria for credentialing in psychedelic-assisted therapies. These recommendations comprise the first step in an essential process to connect science, education, varied entheogen and psychedelic practices and our government. The professional recommendations of the committee culminate in advising the creation of a National Advisory Council, adjunct to the Office of Controlled Substances, Health Canada, and a Credentialing Council adjunct to the National Advisory Council. These councils would advise on sustainability and management of entheogenic plants, and education, training, core clinical competencies, ethical codes of conduct, and credentialing for clinicians and practitioners seeking to provide psychedelic treatment to clients.
... These narrative reviews consistently suggest psychedelics can be safely administered (i.e. adverse effects are minimal and transient) and may reduce depression and anxiety symptoms (Muttoni, Ardissino, & John, 2019), provide psychological benefits in the context of life-threatening disease (Reiche et al., 2018), and induce mystical experiences associated with enduring changes in personality and attitudes (Aday, Mitzkovitz, Bloesch, Davoli, & Davis, 2020). Despite several well-conducted systematic reviews, only two quantitative reviews (i.e. ...
... The search was conducted between October 23rd and 31st, 2019. In addition, we hand searched recent systematic reviews (Aday et al., 2020;Bouso, dos Santos, Alcázar-Córcoles, & Hallak, 2018;dos Santos et al., 2018;Jungaberle et al., 2018;Muttoni et al., 2019;Reiche et al., 2018;Reiff et al., 2020;Schenberg, 2018). ...
Article
Background: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias. Methods: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain. Results: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects. Conclusions: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.
... 3-4), which is consistent with numerous other studies exploring ibogaine (Naranjo, 1969(Naranjo, , 1974Lotsof and Alexander, 2001;Schenberg et al., 2014;Heink et al., 2017;Camlin et al., 2018;Rodger, 2018) and other hallucinogens' effects, such as DMT, LSD, as well as mescaline (Hood, 1975;Griffiths et al., 2008;MacLean et al., 2011). For an up-todate review of long-term effects associated to psychedelic drugs consumption, see Aday et al. (2020). ...
... Positive changes in attitudes and behaviors, increased positive coping, prosociality, and empathy. Negative long-term changes at the neurological, personality, molecular, and psychological level (see Aday et al., 2020). ...
Article
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The concept of transformative experience (TE) has been widely explored by several disciplines from philosophy to neurobiology, and in different domains, from the spiritual to the educational one. This attitude has engendered heterogeneous models to explain this phenomenon. However, a consistent and clear understanding of this construct remains elusive. The aim of this work is to provide an initial comprehensive interdisciplinary, cross-domain, up-to-date, and integrated overview on the concept of TEs. Firstly, all the models and theories on TEs were reviewed to extract and analyze TEs’ main components emerging from different disciplines. Then, this preliminary analysis was integrated with an in-depth examination of redundancies and particularities across domains and disciplines, to provide an integrated theoretical framework of TEs and a preliminary interdisciplinary operational definition of TEs. This examination, in turn, can help organize current research and theories, thus providing suggestions for operationalizing TEs as well as encouraging new interdisciplinary research endeavors.
... A growing body of evidence suggests that long-term changes in psychological functioning might indeed be observed even after a single psychedelic experience and that these changes are mostly beneficial (review from the study by Aday et al., 2020). Healthy participants who received a single dose of psilocybin in the research context reported an increase in well-being and quality of life lasting from several days to months (Griffiths et al., 2008;Uthaug et al., 2018Uthaug et al., , 2019. ...
... Classic psychedelics are able to cause robust changes in perception, cognition, and brain activity (review of the study by Vollenweider and Preller, 2020), and a growing body of evidence indicates that that even a single psychedelic experience might cause lasting psychological effects (review of the study by Aday et al., 2020). It is thus conceivable that using psychedelics frequently in a naturalistic setting is also related to persistent changes in psychological functioning. ...
Article
Background: Psychedelics are able to acutely alter emotional reactivity and self-consciousness. However, whether the regular naturalistic use of psychedelics can be linked to more persistent trait-level changes in these domains remains an open question. Aim: To test the hypotheses that (1) using psychedelics is related to higher positive and lower negative emotional reactivity; and (2) an adaptive pattern of self-consciousness, including diminished public self-consciousness and rumination, and increased reflection and self-awareness; and (3) these relations are mediated by the intensity of past ego-dissolution and mystical experiences. Method: An online survey including questions about the history of psychoactive substance use; questionnaires measuring trait levels of emotional reactivity and self-consciousness; questionnaires for retrospective assessment of ego-dissolution and mystical experiences. Data collected from 2516 participants (1661 psychedelics users) were analyzed using robust linear regression and mediation analysis. Results: A higher number of lifetime uses of psychedelics predicted greater positive and lower negative emotional reactivity; also, in the domain of self-consciousness, it predicted greater reflection and internal state awareness, and reduced rumination tendency and public self-consciousness. Finally, the intensity of past mystical and ego-dissolution experiences mediated almost all the observed relationships between the lifetime number of psychedelics uses and psychological variables. Conclusions: Lifetime psychedelics use predicts an adaptive pattern of trait-level emotional reactivity and self-consciousness. Ego-dissolution and mystical experiences are essential in understanding the long-lasting psychological effects of psychedelics use. Our findings might potentially explain previous observations of increased well-being in psychedelics users.
... A growing body of evidence suggests that long-term changes in psychological functioning might indeed be observed even after a single psychedelic experience and that these changes are mostly beneficial (review from the study by Aday et al., 2020). Healthy participants who received a single dose of psilocybin in the research context reported an increase in well-being and quality of life lasting from several days to months (Griffiths et al., 2008;Uthaug et al., 2018Uthaug et al., , 2019. ...
... Classic psychedelics are able to cause robust changes in perception, cognition, and brain activity (review of the study by Vollenweider and Preller, 2020), and a growing body of evidence indicates that that even a single psychedelic experience might cause lasting psychological effects (review of the study by Aday et al., 2020). It is thus conceivable that using psychedelics frequently in a naturalistic setting is also related to persistent changes in psychological functioning. ...
Preprint
Background: Psychedelics are able to acutely alter emotional reactivity and self-consciousness. However, whether regular, naturalistic use of psychedelics can be linked to more persistent, trait-level changes in these domains remains an open question.Aim: To test three hypotheses: i) psychedelics use is related to higher positive and lower negative emotional reactivity; ii) psychedelics use is related to enhanced inward-focused self-consciousness and diminished outward-focused self-consciousness; iii) these relations are mediated by the intensity of past ego-dissolution and mystical experiences.Methods: Data from 2,516 participants (1,661 psychedelics users) were collected via an online survey. The survey included questions about the history of psychoactive substance use, questionnaires measuring trait-levels of emotional reactivity and self-consciousness, and questionnaires for retrospective assessment of ego-dissolution and mystical experiences. Data were analyzed using robust linear regression and mediation analysis.Results: First, a higher number of lifetime psychedelic experiences predicted greater positive and lower negative emotional reactivity. Second, in the domain of self, it predicted greater reflection and internal self-awareness, and reduced rumination tendency and public self-consciousness. Finally, intensity of past mystical and ego-dissolution experiences mediated almost all observed relationships between the lifetime psychedelics use and psychological variables. Conclusions: Lifetime psychedelics use predicts an adaptive pattern of trait-level emotional reactivity and self-consciousness. The past ego-dissolution and mystical experiences are essential in understanding the long-lasting psychological effects of psychedelics use. Our findings might potentially explain previous observations of increased well-being in psychedelics users.
... Unpleasant emotional experiences, sometimes known as bad trips in their extreme form, are a well-known feature of psychedelic use, and up to a third of patients report fear or anxiety during psychedelic-assisted therapy. 23 However, this is almost exclusively managed via support from session facilitators, though benzodiazepines are available for management as well. To reduce the risk of acute psychosis or mania during sessions, present studies exclude individuals with a prior diagnosis or first-degree family history of manic episode or psychotic disorder. ...
... Some psilocybin trial participants have noted anxiety and depression in the weeks after sessions, though these effects resolved within 1 month. 23 In a 2020 long-term follow-up study of participants from MDMA-assisted therapy trials, 3.1% reported harms at a 12-month follow-up, with the most commonly reported harm being worsened mood. None of these reported harms were severe and all participants reporting them also experienced at least 1 intervention benefit. ...
Article
Background Psychedelic compounds such as LSD, psilocybin and MDMA share a long and complex history with psychiatry. A half century ago psychedelics were widely employed by psychiatrists in investigational and clinical settings, with studies demonstrating promising findings for their use in the treatment of mental illness and substance use disorders. However, concerns were also raised about their abuse potential, as well as other adverse effects. Due to these worries and psychedelics’ association with the counterculture movement, psychedelics were largely outlawed in the United States in 1970, bringing research on their therapeutic potential to a halt. However, in recent years a resurgence of psychedelic research has revealed compelling, though early, evidence for the use of psychedelic-assisted therapy in treating alcohol use disorder, nicotine use disorder, posttraumatic stress disorder and depression. Objective Here we provide an overview of psychiatry’s complicated relationship with psychedelics, while reviewing contemporary findings on psychedelic-assisted therapy, safety of psychedelic-assisted therapy and risks of non-medical use. We also make the case that psychiatry should consider preparing now for the possibility of Food and Drug Administration (FDA) approval of psychedelic-assisted therapies in the near future. We conclude by discussing how growing societal interest in psychedelics could impact the work of C-L psychiatrists, while also exploring how C-L psychiatrists might contribute to future delivery of psychedelic treatments. Conclusions Despite past concerns about psychedelics, current data indicate psychedelic-assisted therapy may potentially reduce suffering due to mental illness and addiction if administered thoughtfully and cautiously by trained professionals in medical settings.
... The largest body of research on use of psychedelics in the context of psychotherapy is on psilocybin, and clinical trials of psilocybin therapy have provided evidence for its effectiveness in addressing cancer-related anxiety and depression, treatment-resistant depression, major depressive disorder, and substance misuse (Agin-Liebes et al. 2020;Bogenschutz et al. 2015Bogenschutz et al. , 20182018;Davis et al. 2020;Griffiths et al. 2016;Johnson and Griffiths 2017;Luoma, Chwyl, Davis, Bathje, & Lancelotta, 2020;Swift et al. 2017). Psilocybin therapy appears to produce benefits in mental health functioning in part because it allows for increased self-awareness, psychological flexibility, and deeply meaningful experiences that are often described as "mystical" or "spiritual" (Aday et al. 2020;Davis et al. 2020;Griffiths et al. 2006). In addition to acute improvements in mental health functioning, the long-term effects of psilocybin have reportedly included an increase in wellbeing and optimism, and a continued decrease in mental health symptoms, for up to 4.5 years after psilocybin treatment (Agin-Liebes et al. 2020;Carhart-Harris et al. 2017;Johnson and Griffiths 2017; Although the US Food and Drug Administration (FDA) has granted "Breakthrough Therapy Status" to two organizations conducting large multi-site trials with this drug (Compass Pathways 2018; Usona Institute 2020), psilocybin remains a schedule I drug. ...
... This paper reports on the results of a quasiexperimental survey study designed to assess psychologists' attitudes toward psychedelics generally, and psilocybin specifically because of its likelihood of being the first drug to be approved for therapeutic use. Because one of the hallmark effects of psilocybin is the mystical or spiritual experience (Aday et al. 2020;Davis et al. 2020;Griffiths et al. 2006), we sought to explore whether attitudes and beliefs about such experiences varied as a function of whether they were (or would be) occasioned naturally (e.g., via meditation or a religious event) or whether they were (or would be) occasioned by psilocybin. Specifically, the present study was designed to examine (1) whether beliefs about working with a client who had a recent spiritual/mystical experience varies as a function of whether these experiences are occasioned by psilocybin or a religious/spiritual event; ...
Article
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Psychologists are a vital component of mental health treatment and their perceptions of psychedelic-assisted therapy are critical for future implementation. This cross-sectional quasi-experimental electronic survey study explored the attitudes about psychedelics used in treatment among 366 clinical psychologists in the United States. Participants expressed cautiously favorable attitudes toward therapeutic psychedelic experiences but indicated concern about possible psychiatric and neurocognitive risks. Most participants indicated that they lack an understanding of the full range of effects of psychedelics, would need to seek out additional consultation, and endorsed positive beliefs in the potential of psychedelic treatment and the need for further research. Overall, this research identified the need to increase education and training about psychedelics for psychologists in order to help increase knowledge and reduce stigma about psychedelic therapies. ARTICLE HISTORY
... Immediate response to treatment with potential long-term effects [57][58] The therapeutic effect diminishes with the withdrawal of substances ...
... The therapeutic effect may persist without continuous application [25,[57][58] Co-treatment regimens with (other) psychotherapists possible, not mandatory ...
Article
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), or dimethyltryptamine (DMT), as well as psychoactive drugs that trigger phenomenologically- related experiences like 3,4-methylenedioxymethamphetamine (MDMA) and ketamine, belong to the most promising treatment approaches in contemporary psychiatry. Psychedelic-assisted psychotherapy is not only a new treatment paradigm in psychopharmacology, but it also requires a redefinition of psychotherapeutic processes and the contextualization of psychopharmacological interventions within a new treatment infrastructure. Crucial for future practice and research in the field are (1) informed patient referral and co-treatment practices, (2) screening (e. g., choosing the right patients for these therapies), (3) the dosing preparation sessions, (4) the assisted dosing sessions as well as after-care procedures such as (5) psychological integration and (6) supporting the development of structured patient communities. Definition of future treatment delivery infrastructures and requirements for therapist training are further challenges for research and practice. Finally, the implementation of psychedelic-assisted psychotherapy in routine mental health care must be embedded into public communication about the potential and risks of these innovative therapeutic approaches. This paper provides a synopsis of challenges for practitioners, researchers, and regulators to be addressed in the approval processes of psychedelics. Publication History Received: 15 February 2021 Received: 06 April 2021 Accepted: 13 April 2021 Publication Date: 12 May 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
... Several studies-many, admittedly, small and preliminary-have reported lasting psychological benefits resulting from one to three administrations of a psychedelic. These benefits encompass reductions in symptoms of anxiety, depression, and addiction, and positive personality change and increases in self-reported well-being in mentally healthy volunteers (Aday et al. 2020). These findings cannot yet be regarded as conclusive. ...
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In this précis I summarise the main ideas of my book Philosophy of Psychedelics . The book discusses philosophical issues arising from the therapeutic use of classic psychedelic drugs such as psilocybin and LSD. The book is organised around what I call the Comforting Delusion Objection to psychedelic therapy: the concern that this novel and promising treatment relies essentially on the induction of non-naturalistic metaphysical beliefs, rendering it epistemically (and perhaps, therefore, ethically) objectionable. In the book I develop a new response to this Objection which involves showing that a popular conception of psychedelics as agents of insight and spirituality is both consistent with a naturalistic worldview and plausible in light of current scientific knowledge. Exotic metaphysical ideas do sometimes come up, but they are not, on closer inspection, the central driver of change in psychedelic therapy. Psychedelics cause therapeutic benefits by altering the sense of self, and changing how people relate to their own minds and lives--not by changing their beliefs about the ultimate nature of reality. Thus, an "Entheogenic Conception" of psychedelics as agents of insight and spirituality can be reconciled with naturalism (the philosophical position that the natural world is all there is). Controlled psychedelic use can lead to genuine forms of knowledge gain and spiritual growth--even if no Cosmic Consciousness or divine Reality exists.
... Such evidence has inherent value in advancing scientific understanding of spiritual and religious variation. Second, such evidence could connect cannabis to a growing literature suggesting that major psychedelics can advance spiritual pursuit (e.g., Aday et al. 2020). Entheogens offer the ability to democratize access to primary spiritual experience, leading to experiential confirmation of belief among the religious, newfound belief in the Divine among hard-core materialists, reduced suicidality, and long-term positive changes in attitudes, behavior, and even core personality traits (Griffiths et al. 2018;Hendricks et al. 2015;Roberts 2014). ...
Article
Like many mind-altering plants, cannabis has been part of spiritual practices for thousands of years. It has deep roots in Hinduism, Islam, Rastafarianism, and indigenous traditions in Asia, Africa, and elsewhere. Yet almost no attention has been given to how contemporary adults employ it spiritually. A sample of 1087 participants (mean age = 38.9) completed an online survey assessing their use of cannabis and other substances, as well as spiritual and psychological characteristics. Spiritual benefit from cannabis was reported by 66.1% of the sample, and 5.5% reported it had sometimes been a spiritual hindrance. A MANOVA showed that those who reported spiritual benefit differed significantly from those who did not on several outcome variables, and a post hoc descriptive discriminant analysis revealed that expansiveness motivation, non-theistic daily spiritual experience, meditation frequency, and two mindfulness facets contributed most to differentiating the two groups. The majority of the sample (63%) was free of cannabis use disorder. Compared to disordered groups, the non-disordered group was significantly older and scored lower on experiential avoidance, psychological distress, and several motives for use. Results suggest that spiritual motives for cannabis use may be widespread. Implications for future research on spiritual use of cannabis are discussed.
... The mechanism behind these benefits for dramatic behavioral change lies in evidence suggesting that psychedelicassisted therapy can engender profound experiences which facilitate long-lasting positive changes in attitudes, mood, altruism, behavior, psychological functioning, life satisfaction, and key personality domains such as openness (Griffiths et al., 2008MacLean et al., 2011). Moreover, findings from studies have also demonstrated that the positive and long-lasting changes often result from just a single dose of a psychedelic substance (Aday et al., 2020;Griffiths et al., 2006;Krebs & Johansen, 2012;MacLean et al., 2011), suggesting that such interventions may be more efficient, low cost, and long-lasting than many existing criminal justice interventions. ...
... The evidence to date suggests that classic psychedelics have immunomodulatory and anti-inflammatory properties (Flanagan and Nichols, 2018;Frecska et al., 2016;Nichols, 2009;Szabo, 2015Szabo, , 2019; carry low risk of adverse effects when administered by health professionals in a safe and supportive environment (Nutt and Carhart-Harris, 2020;Nutt et al., 2010;Rucker et al., 2018); and can be effective in the treatment of depression, anxiety and addiction (Aday et al., 2020;Carhart-Harris et al., 2016, 2018Davis et al., 2020;Goldberg et al., 2020;Johnson et al., 2014;Krebs and Johansen, 2012;Luoma et al., 2020). For example, patients with treatment-resistant depression experienced reductions in depressive symptoms after two oral doses of psilocybin. ...
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Background In recent years, there has been significant research on the mental health effects of classic psychedelic use, but there is very little evidence on how classic psychedelics might influence physical health. Aims The purpose of the present study was to investigate the associations between lifetime classic psychedelic use and markers of physical health. Methods Using data from the National Survey on Drug Use and Health (2015-2018) with 171,766 (unweighted) adults aged 18 or above in the United States, the current study examined the associations between lifetime classic psychedelic use and three markers of physical health (self-reported overall health, body mass index, and heart condition and/or cancer in the past 12 months) while controlling for a range of covariates. Results Respondents who reported having tried a classic psychedelic at least once in their lifetime had significantly higher odds of greater self-reported overall health and significantly lower odds of being overweight or obese versus having a normal weight. The association between lifetime classic psychedelic use and having a heart condition and/or cancer in the past 12 months approached conventional levels of significance, with lower odds of having a heart condition and/or cancer in the past 12 months for respondents who had tried a classic psychedelic at least once. Conclusion The results of the present study suggest that classic psychedelics may be beneficial to physical health. Future research should investigate the causal effects of classic psychedelics on physical health and evaluate possible mechanisms.
... That said, there were no differences in amount of generated ideas or associations in total, or how original responses were. It should also be noted that the effect size on number of novel ideas was moderate (d = 0.52), however, is in accordance with other studies that have found persisting changes in aspects related to DT at various time points relative to consumption of a range of psychedelic drugs (see Aday et al. 71 for a review). ...
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Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking. Acutely, psilocybin increased ratings of (spontaneous) creative insights, while decreasing (deliberate) task-based creativity. Seven days after psilocybin, number of novel ideas increased. Furthermore, we utilized an ultrahigh field multimodal brain imaging approach, and found that acute and persisting effects were predicted by within- and between-network connectivity of the default mode network. Findings add some support to historical claims that psychedelics can influence aspects of the creative process, potentially indicating them as a tool to investigate creativity and subsequent underlying neural mechanisms. Trial NL6007; psilocybin as a tool for enhanced cognitive flexibility; https://www.trialregister.nl/trial/6007.
... Psychedelic and mindfulness-based interventions have both been shown independently to improve mental health and psychological wellbeing. 1,2 While distinct, both psychedelics and mindfulness are associated with a range of similar phenomenological, psychological, and neurobiological changes. 3,4 These similarities reflect potential compatibility as combined interventions. ...
Article
Psychedelic and mindfulness interventions have been shown to improve mental ill-health and wellbeing, with a range of clinical processes and effects in common. However, each appear to contain specific challenges in the context of mental health treatment. In this Perspective, we focus on a set of distinct affordances, “useful differences”, within psychedelic and mindfulness interventions that might address common challenges within the other intervention. Accordingly, we propose a set of applied synergies, indicating specific ways in which these two promising interventions might be combined for greater benefit. Metaphorically, on the journey toward mental health and wellbeing, we propose that psychedelic treatments may serve the role of Compass (initiating, motivating, and steering the course of mindfulness practice), with mindfulness interventions serving the role of Vehicle (integrating, deepening, generalizing, and maintaining the novel perspectives and motivation instigated by psychedelic experience). We outline a set of testable hypotheses and future research associated with the synergistic action of psychedelic and mindfulness interventions toward improved clinical outcomes.
... Serotonergic psychedelics (a subset of 5-HT 2A receptor agonists) are capable of inducing remarkable changes in perception, affect, self-awareness and cognition (Nichols, 2016). Some of the effects elicited by psychedelics are long-lasting, for instance, changes in personality traits and improvements in the symptoms of certain mental health conditions (Bouso et al., 2018;Aday et al., 2020;Nutt and Carhart-Harris, 2021). After decades of neglect, psychedelics have resurfaced into the mainstream of human neuroscience and psychiatry, a revolution spearheaded by neuroimaging studies in healthy volunteers (Dos Santos et al., 2016) and clinical research that supports the efficacy of these drugs for the treatment of depression (Carhart- Harris et al., 2016;Palhano-Fontes et al., 2019;Davis et al., 2020), substance abuse , and existential anxiety (Grob et al., 2011;Griffiths et al., 2016), among other uses. ...
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N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. We combined wireless electroencephalography and source imaging to map changes in neural oscillations elicited by inhaled DMT. Furthermore, we found that the power of frontal and temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. Finally, we established the robustness of these results using a machine learning model for regression trained and tested following a cross-validation procedure. Our results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. We also suggest that priming subjects to reduce their theta power before administration of a serotonergic psychedelic could enhance the likelihood of inducing mystical-type experiences, leading to sustained positive effects in well-being and improving the outcome of therapeutic interventions.
... Self-experiments were included because they were representative of this early period of research and they can be used to provide qualitative information which statistical analyses cannot; however, conclusions from this research can be limited by concerns about ethics, experimenter biases, and generalizability. Other limitations include unstandardized dosages and a lack of direct comparisons between different psychedelic drugs-problems that persist in psychedelic science today (Aday et al. 2020c). Additionally, although researchers today have developed perceptual rating scales with components that parse the constitutive components of the experience (e.g., Strassman et al. 1994), this was typically not the case with earlier research and scales often varied across research groups. ...
Article
Psychedelic drugs are well-known for transiently altering perception, and in particular, for their visual effects. Although scientific interest into the substances’ effects on perception increased during the first era of psychedelic research during the early to mid-20th century, there is currently no source where these findings have been synthesized. In addressing this gap, the current narrative review found that psychedelics were examined for their influences across all levels of the visual system (e.g., retinal, cortical, subcortical, simple visual processing, complex imagery, hallucinations). Psychedelics were also shown to affect auditory discrimination/generalization, neural correlates of auditory processing, and led to auditory hallucinations in subsets of participants. Several studies demonstrated that psychedelics can distort representations of body schema and time perception. Concerns regarding methodological standards of this era are a limitation to the findings and are discussed. Collectively, this review preserves and increases the accessibility of the work done by pioneering psychedelic/perception researchers, synthesizes findings, and critically analyzes areas of discrepancy to inform future studies.
... Results first confirmed that psychedelics lead to a reduction in depression and anxiety (Aday et al., 2020;Luoma et al., 2020;Muttoni et al., 2019;Romeo et al., 2020;Wheeler & Dyer, 2020) that is predicted by the magnitude of psychological insights, and to a lesser degree, by the mystical-type experience that occurred during the psychedelic session (Davis, Averill, et al., 2020;. Moreover, results also showed that psychedelic sessions are followed by inter-correlated changes in self-rumination and self-compassion. ...
Article
Psychedelic experiences can be associated with psychological health improvements, such as decreased depression, anxiety and stress (DAS). Indices indicate that mystical experience and psychological insights, two consistent phenomena of the psychedelics experience, could operate a shift from self-rumination toward self-compassion. Therefore, the present study tests the hypothesis that changes in self-rumination and self-compassion mediate the effects of mystical experience and psychological insights on decreases in DAS following a psychedelic experience. Online questionnaires were completed by individuals who reported having had a significant psychedelic experience (n = 164). We observed significant decreases in DAS after the psychedelic experience. We also observed a significant decrease in self-rumination and increase in self-compassion after the psychedelic experience. A regression analysis showed that the level of psychological insights experienced during the psychedelic session was significantly associated with decrease in DAS. A mediation analysis revealed that decreases in self-rumination and increases in self-compassion partially mediated the effect of psychological insights on decreases in DAS. Although there was an increase in self-reflection following the psychedelic experience, it was not associated with decreases in DAS. This suggests that decreases in self-rumination and increases in self-compassion may be partial mediators of the effects of psychedelics on DAS. Self-compassion shared similarities with psychological flexibility, and self-compassion focused therapies have been shown efficient to decrease DAS. Therefore, we propose that our results bring additional support for the use of contextual behavioral science and related third waves cognitive-behavioral therapies to get the best benefits of psychedelic effects in the context of psychedelic-assisted therapy.
... Similar reductions in depression symptoms have been described with ayahuasca, a brew containing DMT from the Psychotria viridis plant and monoamine oxidase inhibitors from the Banisteriopsis caapi vine (19)(20)(21). In fact, recent systematic reviews have reported signi cant, rapid and sustained reductions in depressive symptoms in all modern trials which utilise either psilocybin or ayahuasca (22,23). Psychedelic therapy offers several advantages over conventional anti-depressant treatment. ...
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Background There is currently renewed interest in the use of psychedelic therapy in the treatment of psychiatric disorders, including depression. The proposed systematic review will aim to identify, evaluate and summarise the psychological processes of change underlying psychedelic therapy for depression in the current literature and consider the implications these processes may have on the psychotherapy component of treatment. Methods Scopus, PsycINFO, PubMed and Web of Science databases will be searched using relevant terms. Studies will be included if they discuss the use of a classic psychedelic to treat depression symptomology in an adult population and report or propose psychological processes responsible for depression symptom change. Two authors will independently screen articles, complete quality assessment tools and conduct data extraction. Empirical and non-empirical research will be extracted and synthesised separately. A narrative synthesis approach will be used to report psychological processes identified in the literature. DiscussionThis systematic review will be the first to collate available evidence on the psychological processes associated with psychedelic therapy for depression. The preliminary nature of this research field is expected to result in the review having several limitations, namely heterogeneity between studies and a lack of empirical research. We intend for this review to present the current state of the literature, identify gaps and generate candidate variables that warrant further investigation. Systematic Review RegistrationPROSPERO CRD42020197202
... A series of 12 relevant articles were localized in a book about microdosing psychedelics (n = 4), [27][28][29][30][31][32][33][34] and a review paper describing the long-term effects of psychedelics (n = 1) and in my personal database (n = 7) was added. 35 The oldest articles (n = 4) were harvested from the bibliographic database of the Multidisciplinary Association for Psychedelic Studies (https://maps.org/resources/ psychedelic-bibliography), the rest (n = 8) via google scholar; 10 papers were excluded as they were based on claims of microdosers and not experimental research. ...
Article
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Microdosing psychedelics is the repeated use of small doses of, for example, lysergic acid diethylamide (LSD) and psilocybin, typically for a few weeks. Despite the popular and scientific attention in recent years, and claims by users that it has therapeutic value in affective disorders like depression, little scientific knowledge is available to back this. The purpose of this review was to investigate whether there are scientific grounds to state that this practice could be helpful in the treatment of affective disorders, and safe to use repeatedly. To that end, the literature (PubMed, MedLine) was searched, looking for (controlled) experimental studies with low doses of LSD and/or psilocybin, in healthy volunteers and patient samples. After a selection process and the addition of relevant articles, 14 experimental studies entered this review. Findings show that both LSD (10–20 mcg) and psilocybin (
... Other studies have found evidence of lasting psychological benefits in healthy subjects following controlled psychedelic administration (Gandy 2019). Thus, it is a plausible scientific hypothesis that one, or very few, carefully conducted psychedelic sessions can lead reliably to psychological benefits lasting months or even years, without serious or lasting adverse effects (Aday et al. 2020). Interestingly, such lasting benefits seem to be predicted by the occurrence of a "mystical-type" experience of oneness or cosmic unity, or an experience of "psychological insight", during the drug effects (Letheby 2021). ...
Chapter
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Psychedelic ingestion and meditative practice are both ancient methods for altering consciousness that became widely known in Western society in the second half of the 20th century. Do the similarities begin and end there, or do these methods – as many have claimed over the years – share some deeper common elements? In this chapter I take a neurophilosophical approach to this question and argue that there are, indeed, deeper commonalities. Recent empirical studies show that psychedelics and meditation modulate overlapping brain networks involved in the sense of self, salience, and attention; moreover, psychedelics can occasion lasting increases in “mindfulness-related capacities” for taking a non-reactive stance on one’s inner experience (e.g. Sampedro et al. 2017). The self-binding theory of psychedelic ego dissolution (Letheby and Gerrans 2017) offers a plausible explanation of these findings: by disrupting self-related beliefs implemented in high-level cortical networks, both psychedelics and meditation can “unbind” mental contents from one’s self-model, moving these contents along the continuum from phenomenal transparency to opacity (cf. Metzinger 2003). In other words, both psychedelics and meditation can expose and weaken our foundational beliefs about our own identity, allowing us to disidentify with these beliefs and see them as “just thoughts”. There are connections between these ideas and recent arguments suggesting that psychedelic use may have epistemic benefits consistent with philosophical naturalism (Letheby 2015, 2016, 2019). I conclude with a proposal: these connections may help in thinking about the putative epistemic benefits of meditation practice from a naturalistic perspective.
... Within the United States, psilocybin is classified as a Schedule 1 substance under the Controlled Substance Act and is considered to be illegal under Federal law. Meanwhile, a growing body of research indicates that there may be a therapeutic benefit to the use of psilocybin (Aday et al. 2020b;Andersen et al. 2021;Johnson et al. 2019). ...
Article
There is a growing body of research suggesting that palliative care patients coping with existential distress may benefit from psilocybin. However, there is a large gap regarding the perceptions of palliative care providers who may provide education, counseling services, recommendations, and/or prescriptions for psilocybin if it is decriminalized, commercialized, and/or federally rescheduled and legalized. The aim of this study was to explore the experiences and perceptions of interdisciplinary palliative care providers regarding existential distress and the use of psilocybin therapy. Five (n = 5) health care providers from a hospital-based palliative care team completed a semi-structured interview related to their experiences supporting patients with existential distress and their beliefs and attitudes related to psilocybin as a possible treatment modality. A qualitative descriptive approach was used to identify key themes which included: 1) multiple barriers to addressing existential distress at the cultural, institutional/organizational, relational, and individual levels, 2) the duality and power of presence, 3) suffering as an intrinsically subjective phenomenon, and 4) uncertainty about the risks and benefits of psilocybin. To inform an inclusive, safe, and holistic approach, more research is needed regarding the possible integration of psilocybin therapy within palliative care for the treatment of existential distress.
... While many persisting psychological effects of SP use have been investigated (Aday et al., 2020), neuropsychological consequences remain underexplored. Even though acute effects of SPs include impairment of neuropsychological performance (Gouzoulis-Mayfrank et al., 2002Bouso et al., 2013;Barrett et al., 2018;Pokorny et al., 2019;Healy, 2021), so far only one systematic review has investigated persisting effects of SP use on neuropsychological functioning (Halpern and Pope, 1999). ...
Article
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Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT 2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. Results: 13 studies (N 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n 343), LSD (5 studies, n 135), and peyote (1 study, n 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p 0.03) and no differences in the others (all p > 0.05). Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.
... Early clinical studies on psilocin have shown a wide variability in drug response 35 (S12N, T25N, D48N, I197V, A230T, A447V, and H452Y) have potential actions on both receptor structure and function 36 . As shown in Figure 1, the S12N, T25N, and D48N SNPs map to the predicted N-terminal tail of the receptor; the I197V SNP resides in the fourth transmembrane helix; the A230T SNP resides in the putative second extracellular loop (ECL2); the two remaining non-synonymous SNPs (A447V and H452Y) are located within the putative C-terminal tail. ...
Preprint
Serotonin (5-Hydroxytryptamine; 5-HT) 2A receptor (5-HT 2A R) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT 2A R affect the signaling of four commonly used psychedelic drugs. We examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to S12N, T25N, D48N, I197V, A230T, A447V, and H452Y variant 5-HT 2A serotonin receptors. We found that these non-synonymous SNPs exert statistically significant, although modest, effects on the efficacy and potency of four therapeutically relevant hallucinogens. Significantly, the in vitro pharmacological effects of the SNPs drug actions at 5-HT 2A R are drug specific. Table of Contents/Abstract Graphic
... Learning more about the necessary neural or physiological bases to these experiences may help in reproducing them, but that does not relate to the doctrines that mystics espouse. 9 In addition to aiding in establishing the uniqueness of mystical experiences, the beneficial effects of meditation and psychedelics such as psilocybin and LSD in aiding such psychological problems as depression and addiction are now being demonstrated (e.g., Aday et al. 2020). Neuroscience appears to validate the positive effects of meditation and psychedelic therapy on our well-being. ...
Article
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How a positive naturalist understanding of mystical experiences is possible and how these experiences and accompanying practices can be incorporated into a secular mysticism are discussed. Philosophical issues related to such a secular mysticism are also raised: is a truly secular mysticism possible? Are mystical experiences cognitive of transcendent non-natural realities? Can secular mysticism address the issue of the possible construction of mystical experiences? Can one find meaning or a purpose to life when non-natural realities and life after death are not parts of the picture?
... Mindfulness meditation and psychedelics, for instance, both disrupt the DMN with lasting positive impacts such as reducing anxiety and addictive cravings. These transcendent states give people distance from their habitual thoughts and behavior and boost equanimity and pro-social behavior (106)(107)(108)(109)111,112). These kinds of experiences can be accessed through meditation and psychedelics, but neuroimaging and neuromodulation are identifying which parts of the brain are key to such experiences. ...
Chapter
This paper discusses the potential for brain stimulation and brain-computer interfaces to modulate moral emotions, cognition, and behavior. Links between brain structures and moral cognition began with studies of victims of brain injuries and became more precise with advances in brain imaging. In the last two decades, research has demonstrated that moral emotions and cognition can be modulated with internal and external stimulation focused on particular brain structures. Non-invasive methods of neuromodulation include focusing electrical current or magnetism through the skull, while invasive procedures include implanting electrodes, sensors, and computer chips in the brain. As brain-computer interfaces (BCIs) become smaller, safer, more powerful, and more interactive, the healthy will eventually be able to use arrays of sensors and electrodes to sense, inhibit and boost moral thoughts and emotions. Individuals with brain disorders that lead to violence and criminality, for instance, could be offered BCI therapy as an alternative to psychiatric treatment or incarceration. This essay proposes a model of six virtues that could be neuromodulation targets: self-control, caring, intelligence, positivity, fairness, and transcendence. Research on the neuromodulation of each virtue is reviewed.
... As research with psychedelics is expanding worldwide in clinical and nonclinical samples (for reviews, see Aday et al. 2020;Berkovitch et al. 2021;Gandy 2019;Goldberg et al. 2020;Luoma et al. 2020;Muttoni, Ardissino, and John 2019;Romeo et al. 2021Romeo et al. , 2020Sueur 2017;Wheeler and Dyer 2020), there is a need to translate and validate the instruments used for measuring the phenomenology of the psychedelic experience. An adapted version of the MEQ30 has already been validated in Finnish (Kangaslampi, Hausen, and Rauteenmaa 2020), but no version exists in French yet. ...
Article
Mystical experiences triggered by psychedelic drugs predict symptom reduction in various psychiatric disorders, and increased well-being in healthy individuals. This work aimed at validating a French version of a tool used to measure mystical experiences: the Revised Mystical Experience Questionnaire-30 items (MEQ30). Construct validity, internal consistencies, concurrent, discriminant, and predictive validities of the French MEQ30 were examined using data about the most significant psychedelic experience of 320 French individuals. Results showed that the original four-factor (i.e., mystical, positive mood, transcendence, and ineffability) structure fit the data best, with good to excellent statistical indices. Total French MEQ30 score was strongly associated with subjective ratings of the mystical (i.e., mystical, spiritual, or religious, and personally significant) and drug intensity-related qualities of the experience, but not with non-mystical (i.e., fun, inebriating, and easy) qualities. Moreover, French MEQ30 score was a significant predictor of subjective positive changes in psychological well-being, relations with self and others, feeling of proximity or connection with nature, and creativity, whereas drug intensity-related and non-mystical qualities of the experience were not, or were only weakly associated with such changes. This French version of the MEQ30 seems to be an appropriate tool for measuring mystical experiences among French speaking individuals.
... A growing body of evidence supports the potential utility of psychedelic compounds for aiding the treatment of numerous psychiatric disorders (for reviews, see Aday et al., 2020;Andersen et al., 2021;Carhart-Harris and Goodwin, 2017). Although the therapeutic promise of psychedelics is receiving growing empirical support, the mechanisms through which psychological outcomes occur are less well understood (Carhart-Harris, 2019;Nutt et al., 2020). ...
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Introduction As their name suggests, ‘psychedelic’ (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS). Methods The PIS is a six- to seven-item questionnaire that enquires about psychological insight after a psychedelic experience (PIS-6) and accompanied behavioural changes (PIS item 7). In total, 886 participants took part in a study in which the PIS and other questionnaires were completed in a prospective fashion in relation to a planned psychedelic experience. For validation purposes, data from 279 participants were analysed from a non-specific ‘global psychedelic survey’ study. Results Principal components analysis of PIS scores revealed a principal component explaining 73.57% of the variance, which displayed high internal consistency at multiple timepoints throughout the study (average Cronbach’s α = 0.94). Criterion validity was confirmed using the global psychedelic survey study, and convergent validity was confirmed via the Therapeutic-Realizations Scale. Furthermore, PIS scores significantly mediated the relationship between emotional breakthrough and long-term well-being. Conclusion The PIS is complementary to current subjective measures used in psychedelic studies, most of which are completed in relation to the acute experience. Insight – as measured by the PIS – was found to be a key mediator of long-term psychological outcomes following a psychedelic experience. Future research may investigate how insight varies throughout a psychedelic process, its underlying neurobiology and how it impacts behaviour and mental health.
... A major weakness of crossover designs, however, is the potential for carryover effects (i.e., the therapeutic benefits could "carryover" after the first treatment and misrepresent the true effect of the second treatment). Carryover effects are especially concerning in psychedelic trials because the effects of psychedelic therapy in some cases have been shown to be durable for over a year (Griffiths et al. 2008;Johnson et al. 2017; see Aday et al. 2020b for review). Thus, even a 12-month washout period is unlikely to achieve a return to pre-treatment levels on the variable of interest, which biases within-person analyses and threatens the validity of conclusions that can be drawn. ...
Article
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Rationale Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research. Objective In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research. Results Although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants’ expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies are discussed in the context of study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy. Conclusion Incorporating the recommended design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increases the ability to discern treatment-specific effects of psychedelic therapy.
... A systematic review on long-term effects of psychedelics in general included nine studies investigating psilocybin treatment in depressed patients. In the majority of patients, a short-term reduction in depressive symptoms was found, which was sustained for the follow-up period of six months, as investigated by five of the included studies [82]. Another systematic review examined the use of psychedelics for the treatment of depression and anxiety. ...
Article
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There has recently been a renewal of interest in psychedelic research on the use of psilocybin in psychiatric treatment and, in particular, for the treatment of major depressive disorder (MDD). Several state-of-the-art studies have provided new insight into the mechanisms of action of psilocybin and its therapeutic potential. Nevertheless, many questions remain unanswered. With this review, we provide an overview of the current state of research on the potential mechanisms of psilocybin, its antidepressant potential, and the associated risks and adverse effects, to provide an update on a controversial topic discussed in psychopharmacology. A database search was conducted in Medline including articles on psilocybin over the period of the last 20 years. Despite the promising progress in understanding the mechanisms of psilocybin, the exact antidepressive mechanism and the role of the psychedelic experience remain elusive. The studies included in this review found high treatment effect sizes for psilocybin as an antidepressant. However, the results must be regarded as preliminary due to several limitations. Although the current studies observed no severe adverse events, several questions regarding safety and utility remain and must be subject of future research.
... Serotonergic psychedelics (a subset of 5-HT 2A receptor agonists) are capable of inducing remarkable changes in perception, affect, self-awareness and cognition (1). Some of the effects elicited by psychedelics are long-lasting, for instance, changes in personality traits and improvements in the symptoms of certain mental health conditions (2)(3)(4). After decades of neglect, psychedelics have resurfaced into the mainstream of human neuroscience and psychiatry, a revolution spearheaded by neuroimaging studies in healthy volunteers (5) and clinical research that supports the efficacy of these drugs for the treatment of depression (6)(7)(8), substance abuse (9), and existential anxiety (10,11), among other uses. ...
Article
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N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. The present study investigated changes in neural oscillations elicited by inhaled DMT, and whether baseline electroencephalography (EEG) recordings could predict the subjective effects reported by the participants. Healthy volunteers ( N = 35) were measured with EEG before and during the acute effects of DMT consumed in a natural setting. Source-localized neural oscillations were correlated with the results of multiple questionnaires employed to assess the subjective effects of the drug. DMT resulted in a marked reduction of alpha and beta oscillations, and increased posterior spectral power in the delta, theta and gamma bands. The power of fronto-temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. The robustness of these results was supported using a machine learning model for regression trained and tested following a cross-validation procedure. These results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. They also suggest that baseline EEG screenings before administration of a serotonergic psychedelic could be useful to estimate the likelihood of inducing mystical-type experiences, previously linked to sustained positive effects in well-being and improved outcome of therapeutic interventions.
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Rationale: Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research. Objective: In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research. Results: We found that although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants’ expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies concern study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy. Conclusion: Incorporating these design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increase the ability to discern treatment-specific effects of psychedelic therapy
Article
Positive emotions feel good and build psychological, social, and biological resources (Broaden-and-Build Theory, Fredrickson, 1998, 2013). People who identify as religious or spiritual value them and report feeling them frequently. They are also prevalent in religious and spiritual practices, such as prayer, meditation, and collective worship. We review the literature on the reciprocal relationship between positive emotions and religion/spirituality and identify individual differences predicting greater positive emotions derived from engaging in religious practices. We suggest that beyond building religious/spiritual people’s well-being, positive emotions play a role in sustaining otherwise costly religious behaviors. We integrate our review in the proposed Upward Spiral Theory of Sustained Religious Practice.
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Older adulthood can be characterized by various cognitive and affective changes. In general, older adults show declines in creativity and executive functioning. They also score lower in openness to experience, empathy, and many suffer from a paucity of meaningful experiences. Further, depression, pessimism, and suicide can be major concerns for this population. Although currently there are few interventions that can effectively address these changes, recent findings from psychedelic science suggest myriad parallels between the effects of these drugs and the cognitive/affective shifts seen in older adulthood. Studies have shown that psychedelics are associated with enhanced creativity and executive functioning. They can also lead to increases in openness and empathy, and induce personally meaningful experiences. Lastly, psychedelics’ efficacy for treating mood disorders and their role in palliative care are rapidly growing areas of scientific research. In this article, we analyze findings from contemporary psychedelic studies and integrate them with research on cognitive/affective changes in older adulthood to assess whether these drugs have potential to be incorporated into older adult research. We also assess the intuitive follow-up questions of potential mechanisms of action and safety concerns. Findings indicate that psychedelics have effects on a number of cognitive/affective processes that are altered in older adulthood, and are relatively safe when used with professional preparation and supervision. Increased neuroplasticity, neurogenesis, connectedness, and mystical experiences have been argued to underlie cognitive/affective changes. However, further research is needed to overcome current experimental limitations such as generalizability, unstandardized dosages, inadequate controls, and self-selection/experimenter biases.
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Background: Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. Methods: Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). Results: Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being (r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases. Conclusions: Here we validate a six-item ‘Emotional Breakthrough Inventory’. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.
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In recent years, the study of psychedelic science has resurfaced as scientists and therapists are again exploring its potential to treat an array of psychiatric conditions such as depression, posttraumatic stress disorder, and addiction. The scientific progress and clinical promise of this movement owes much of its success to the history of indigenous healing practices; yet the work of indigenous people, ethnic and racial minorities, women, and other disenfranchised groups is often not supported or highlighted in the mainstream narrative of psychedelic medicine. The review addresses this issue directly, first by highlighting the traditional role of psychedelic plants and briefly summarizing the history of psychedelic medicine; Secondly, through exploring the historical sociocultural factors that have contributed to unequal research participation and treatment, thereby limiting the opportunities for minorities to be acknowledged for their contributions. Finally, the review provides recommendations for broadening the Western medical framework of healing to include a cultural focus and additional considerations for an inclusive approach to treatment development and dissemination for future studies.
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Creative thinking and empathy are crucial for everyday interactions and subjective well-being. This is emphasized by studies showing a reduction in these skills in populations where social interaction and subjective well-being are significantly compromised (e.g., depression). Anecdotal reports and recent studies suggest that a single administration of psilocybin can enhance such processes and could therefore be a potential treatment. However, it has yet to be assessed whether effects outlast acute intoxication. The present study aimed to assess the sub-acute effects of psilocybin on creative thinking, empathy, and well-being. Participants attending a psilocybin retreat completed tests of creative (convergent and divergent) thinking and empathy, and the satisfaction with life scale on three occasions: before ingesting psilocybin (N = 55), the morning after (N = 50), and seven days after (N = 22). Results indicated that psilocybin enhanced divergent thinking and emotional empathy the morning after use. Enhancements in convergent thinking, valence-specific emotional empathy, and well-being persisted seven days after use. Sub-acute changes in empathy correlated with changes in well-being. The study demonstrates that a single administration of psilocybin in a social setting may be associated with sub-acute enhancement of creative thinking, empathy, and subjective well-being. Future research should test whether these effects contribute to the therapeutic effects in clinical populations.
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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.
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In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices. Finally, we consider long-term outcomes of experiences of self-loss induced by meditation and psychedelics on individual traits and prosocial behavior. We call for caution regarding the problematic conflation of temporary states of self-loss with “selflessness” as a behavioral or social trait, although there is preliminary evidence that correlations between short-term experiences of self-loss and long-term trait alterations may exist.
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The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.
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Rationale Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. Objectives The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca. Results Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca. Conclusion It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.
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Background: Despite renewed interest in studying the safety and efficacy of psychedelic-assisted psychotherapy for the treatment of psychological disorders, the enrollment of racially diverse participants and the unique presentation of psychopathology in this population has not been a focus of this potentially ground-breaking area of research. In 1993, the United States National Institutes of Health issued a mandate that funded research must include participants of color and proposals must include methods for achieving diverse samples. Methods: A methodological search of psychedelic studies from 1993 to 2017 was conducted to evaluate ethnoracial differences in inclusion and effective methods of recruiting peopple of color. Results: Of the 18 studies that met full criteria (n = 282 participants), 82.3% of the participants were non-Hispanic White, 2.5% were African-American, 2.1% were of Latino origin, 1.8% were of Asian origin, 4.6% were of indigenous origin, 4.6% were of mixed race, 1.8% identified their race as "other," and the ethnicity of 8.2% of participants was unknown. There were no significant differences in recruitment methodologies between those studies that had higher (> 20%) rates of inclusion. Conclusions: As minorities are greatly underrepresented in psychedelic medicine studies, reported treatment outcomes may not generalize to all ethnic and cultural groups. Inclusion of minorities in futures studies and improved recruitment strategies are necessary to better understand the efficacy of psychedelic-assisted psychotherapy in people of color and provide all with equal opportunities for involvement in this potentially promising treatment paradigm.
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Mental disorders are rising while development of novel psychiatric medications is declining. This stall in innovation has also been linked with intense debates on the current diagnostics and explanations for mental disorders, together constituting a paradigmatic crisis. A radical innovation is psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs. Clinical results so far have shown safety and efficacy, even for “treatment resistant” conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness.
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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.
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Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.
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The revitalization of clinical trials with psychedelics has produced an array of studies investigating different combinations of therapeutic substances and diagnoses. In addition to the bureaucratic negotiations to gain approval for this research, this new wave of studies is also negotiating a new methodological landscape of clinical research. Mid-twentieth century research with drugs like LSD and psilocybin involved both case studies and double-blind studies. However, today, placebo-controlled randomized controlled trials (RCTs) are the institutional standard for research with psychopharmaceuticals. Because psychedelic therapy seeks to induce a radical change in consciousness—to make a subject feel different from her everyday self—blinding these studies using placebo controls has emerged as a methodological sticking point. However, this chapter argues, it is also a rich site for interrogating boundary work around science and psychedelics. While anthropologists have examined placebos as examples of the power of symbolic healing within Western medicine, or as ethically fraught territory of nontreatment, this chapter examines placebos as a research technique around which the scientific status of a study is negotiated. While psychedelic therapy challenges the model of pharmaceutical intervention used in psychiatry today, it must do so while also working within psychopharmacology’s evidentiary norms.
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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.
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After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased “spaciousness” or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.
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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.
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Rationale: Recent studies have supported the safety and efficacy of psychedelic therapy for mood disorders and addiction. Music is considered an important component in the treatment model, but little empirical research has been done to examine the magnitude and nature of its therapeutic role. Objectives: The present study assessed the influence of music on the acute experience and clinical outcomes of psychedelic therapy. Methods: Semi-structured interviews inquired about the different ways in which music influenced the experience of 19 patients undergoing psychedelic therapy with psilocybin for treatment-resistant depression. Interpretative phenomenological analysis was applied to the interview data to identify salient themes. In addition, ratings were given for each patient for the extent to which they expressed "liking," "resonance" (the music being experienced as "harmonious" with the emotional state of the listener), and "openness" (acceptance of the music-evoked experience). Results: Analyses of the interviews revealed that the music had both "welcome" and "unwelcome" influences on patients' subjective experiences. Welcome influences included the evocation of personally meaningful and therapeutically useful emotion and mental imagery, a sense of guidance, openness, and the promotion of calm and a sense of safety. Conversely, unwelcome influences included the evocation of unpleasant emotion and imagery, a sense of being misguided and resistance. Correlation analyses showed that patients' experience of the music was associated with the occurrence of "mystical experiences" and "insightfulness." Crucially, the nature of the music experience was significantly predictive of reductions in depression 1 week after psilocybin, whereas general drug intensity was not. Conclusions: This study indicates that music plays a central therapeutic function in psychedelic therapy.
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Rationale: Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Aim: Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). Methods: This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Results: Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. Conclusions: This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small st