Article

Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression

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Abstract

Objective: To identify patients’ perceptions of the value of psilocybin as a treatment for depression. Method: Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments. Results: Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance. Conclusions: These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.

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... People often describe this experience as one of the most meaningful and transformative ones in their lives . The experience is often imbued with feelings of intense love and connectedness -directed at close others, humanity, and the world at large (Carhart- Watts et al., 2017) -and a greater ability to engage with an expanded repertoire of emotions, including previously repressed distressing emotions, such as grief (Belser et al., 2017). People also report gaining new perspectives and deeper insight (e.g., into their habitual thoughts and coping methods), experience emotional breakthroughs (Roseman et al., 2019), or other sudden gains in clinically relevant phenomena (e.g., a shift in self-perception that reduces selfcriticism and increases self-compassion, Lafrance et al., 2017;see Breeksema et al., 2020, for a review). ...
... The way people process and integrate their psychedelic experiences depends on the interpretive lens provided by their preexisting metaphysical or religious beliefs (Granqvist, 2020), though this processing may also be affected by psychedelics (e.g., moving people from materialist to non-materialist beliefs; Timmermann et al., 2021). Whether or not interpreted religiously, RSMEs, especially those Stace (1960) called extrovertive states, are associated with relational themes associated with attachment, such as a sense of connection and unity (Granqvist, 2020;Griffiths et al., 2018;Watts et al., 2017;Yaden et al., 2017). ...
... While internal stimuli may retain their painful quality, with adjacent psychological support, psychedelics can be used to address and overcome experiential avoidance and to enable a closer contact with inner experiences and deeper processing of all types of feeling states. Over time, these improvements in mindfulness-related phenomena may improve distress tolerance and behavioral activation for valued ends (Watts et al., 2017). ...
... Psilocybin treatment has had encouraging results in terms of efficacy, in medium and large doses, especially with adjunctive therapy and careful observation during therapeutic dosing [17,22,23,25,26]. In many studies, the safety and toxicity of psilocybin have been primary goals to show that it is a safe and valid therapeutic alternative to other forms of psychiatric medications. ...
... Psilocybin dosing was done with patients who have depression, anxiety, and/or substance use disorder, with most being resistant to at least one other first-line treatment. The current open-label trials have shown a pervasive pattern of individuals not only not needing to take psilocybin everyday, differing from other forms of treatment, but that many patients achieve remission to their condition for a period of time after completion [12,23,25,26]. The need for further research is indicated with more conservative measures and controls and should be attempted to rule out any confounds. ...
... The need for further research is indicated with more conservative measures and controls and should be attempted to rule out any confounds. Different treatment regimens to determine the best way to apply psilocybin in a clinical setting is the next step suggested in other studies [24,25]. The other potentially positive effect of psilocybin use is indicating what part of the mechanism of action in conjunction with therapy helps create remission. ...
... It has been referred to by different names from oceanic boundlessness (OBN; Dittrich, 1998) to unitive experience to oneness (Hayes et al., 2020). Use of the term "connectedness" to refer to this phenomenon, as proposed by Watts et al. (2017), seems particularly useful for clinically-oriented psychedelic research as it stands in opposition to disconnectedness, a detrimental state commonly reported by depressed patients before undergoing psychedelic therapy . Secondly, the related Watts Connectedness Scale (Watts et al., 2022) distinguishes between three distinct kinds of connectedness: with self, with others, and with the world. ...
... Participants reported many lasting effects of the experience, e.g., love for nature, sense of responsibility for others' wellbeing or for the Earth. Watts et al., (2017) Qualitative. Clear guiding questions for the interviews stated in the paper. ...
... Different types of connectedness were reported across the included papers, usually several kinds within a study. Thus, a sense of unity with others during the experience was mentioned in four papers (Agin-Liebes, Ekman, et al., 2021;Amada et al., 2020;Belser et al., 2017;Watts et al., 2017). Among them, Agin-Liebes, Ekman, et al. (2021) was the only study where the psychedelic sessions were carried out in group setting which enabled the experience of connectedness with other cohort members. ...
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Background and aims Despite promising findings indicating the therapeutic potential of psychedelic experience across a variety of domains, the mechanisms and factors affecting its efficacy remain unclear. The present paper explores this by focusing on two psychedelic states which have been suggested as therapeutically significant in past literature: ego-dissolution and connectedness. The aim of the study is to investigate the impact of ego-dissolution and connectedness on the therapeutic effects of the psychedelic experience. Methods The investigation was carried out as a mixed methods systematic review, with the data from four databases analysed thematically and results presented through narrative synthesis. Results The analysis and synthesis of findings from 15 unique studies ( n = 2,182) indicated that both ego-dissolution and connectedness are associated with a higher chance of improvement following a psychedelic experience. However, there seem to be differences in the way the two experiences affect individuals psychologically. Ego-dissolution appears to trigger psychological change but does not typically exceed the psychedelic experience in its duration, while connectedness can be more sustained and is associated with several positive, potentially therapeutic feelings. Conclusions Moreover, the findings of this review have implications for further theory-building about the mechanisms which enable therapeutic effects in psychedelic experience. This in turn might lead to improved models for psychedelic therapy practice. Emphasis on ego-dissolution during the preparation phase and on connectedness during integration is one suggestion presented here, alongside overarching implications for the mental health debate and general practice.
... More overtly, long-term follow-up interviews in patients with treatment-resistant depression (TRD) after psilocybin-assisted therapy display many themes consistent with broaden-and-build theory (Watts et al., 2017). Themes of reconnecting to past activities or starting new ones and "discovering new values/perspectives" were noted, suggesting increases in thought-action repertoire. ...
... (Dass and Das, 2021, p. 67) In this quotation, despite Alpert's sense of loss of identity, he does not express feeling nonexistent as people in psychotic states often report (Parnas and Handest, 2003;Parnas et al., 2005;Sass, 2017). However, the potential role of self-presence in classic psychedelic states has largely been neglected by research, but has been hinted at in qualitative studies Watts et al., 2017). We suggest that this phenomenon be explored further, and to do so will likely require lenses other than psychoanalytic theory (i.e., ego dissolution). ...
... I had fresh insight into things. It was almost as if suddenly the scales dropped from my eyes, I could see things as they really are" (Watts et al., 2017). ...
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The extremes of human experiences, such as those occasioned by classic psychedelics and psychosis, provide a rich contrast for understanding how components of these experiences impact well-being. In recent years, research has suggested that classic psychedelics display the potential to promote positive enduring psychologic and behavioral changes in clinical and nonclinical populations. Paradoxically, classic psychedelics have been described as psychotomimetics. This review offers a putative solution to this paradox by providing a theory of how classic psychedelics often facilitate persistent increases in well-being, whereas psychosis leads down a "darker" path. This will be done by providing an overview of the overlap between the states (i.e., entropic processing) and their core differences (i.e., self-focus). In brief, entropic processing can be defined as an enhanced overall attentional scope and decreased predictability in processing stimuli facilitating a hyperassociative style of thinking. However, the outcomes of entropic states vary depending on level of self-focus, or the degree to which the associations and information being processed are evaluated in a self-referential manner. We also describe potential points of overlap with less extreme experiences, such as creative thinking and positive emotion-induction. Self-entropic broadening theory offers a heuristically valuable perspective on classic psychedelics and their lasting effects and relation to other states by creating a novel synthesis of contemporary theories in psychology. SIGNIFICANCE STATEMENT: Self-entropic broadening theory provides a novel theory examining the psychedelic-psychotomimetic paradox, or how classic psychedelics can be therapeutic, yet mimic symptoms of psychosis. It also posits a framework for understanding the transdiagnostic applicability of classic psychedelics. We hope this model invigorates the field to provide more rigorous comparisons between classic psychedelic-induced states and psychosis and further examinations of how classic psychedelics facilitate long-term change. As a more psychedelic future of psychiatry appears imminent, a model that addresses these long-standing questions is crucial.
... For example, increased AMG activation was found after treating (treatment-resistant) depression with psilocybin (Roseman et al., 2018a). This effect was attributed to acceptance and emotional reconnection reported by patients (Watts et al., 2017;Roseman et al., 2018a). Conversely, another psilocybin study associated positive mood change in healthy subjects, with decreased AMG response measured acutely (Kraehenmann et al., 2015a). ...
... Follow-up research measuring psilocybin effects 1 day after intake suggests that AMG activity increases are accompanied by decreased connectivity between the prefrontal cortex and the AMG . Although this research did not determine the direction of influence, the authors propose connectivity involving the AMG may be an important mechanism underlying previously reported therapeutic outcomes of emotional reconnection (Watts et al., 2017). ...
... The interaction between cognition and emotion may help disarm maladaptive ego defenses. In the context of psychedelic therapy, supportive preparation Neural Mechanisms of Psychedelic Ego Dissolution and prior application of behavioral therapies may also disarm maladaptive ego defenses and help guide positively felt ego dissolution and facilitate cognitiveemotional engagement , emotional reconnection (Watts et al., 2017), and a sense of being attuned with one's emotions (Roseman et al., 2018a). ...
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Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organization and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5-HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message-passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics: in particular, their influence on selfhood and subject-object boundaries—known as ego dissolution—surmised to underwrite their subjective and therapeutic effects. Agonism of 5-HT2A recep-tors, located at the apex of the cortical hierarchy, may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half-life, suggesting that psychedelics may have effects on neural plasticity that may play a role in their therapeutic efficacy. Psychologi-cally, this may be accompanied by a disarming of ego resistance that increases the repertoire of perceptual hypotheses and affords alternate pathways for thought and behavior, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging. Significance Statement——Classic psychedelics bind to serotonergic 5-HT2A receptors. Their agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy, resulting in a profound effect on information processing in the brain. Here, we synthesize an abundance of brain imaging research with pharmacological and psychological interpretations informed by the framework of predictive coding. Moreover, predictive coding is suggested to offer more sophisticated interpretations of neuroimaging find-ings by bridging the role between the 5-HT2A receptors and large-scale brain networks.
... 11 Psychedelics have been shown to reduce negative appraisals, 12 and qualitative reports from clinical research suggest a decrease in self-rumination and increase in acceptance of emotions after a psychedelic experience. 13 However, no study to date has assessed the impact of psilocybin on clinical measures of rumination and thought suppression in an RCT with blinding procedures and an established antidepressant treatment as an active comparator. Here, we bridge this gap by using the 22-item Ruminative Response Scale (RRS) 14 and 14-item White Bear Suppression Inventory (WBSI) 4 in a trial of 59 patients with MDD treated with either psilocybin therapy or escitalopram. ...
... Depressive symptoms were assessed with the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR-16). 15 The total score establishes the severity of depression, ranging from 'absent' (0-5) to 'mild' (6-10), 'moderate' (11)(12)(13)(14)(15), 'severe' (16)(17)(18)(19)(20) and 'very severe' (21)(22)(23)(24)(25)(26)(27). Treatment response at 6 weeks was defined as at least a 50% drop from baseline score on the QIDS-SR-16 (coded as 1 for response or 0 for no response). ...
... Reductions in rumination significantly correlated with reductions in depressive symptoms in both groups, and more participants in the psilocybin group (21 out of 30) compared with the escitalopram group (14 out of 29) were classified as responders. The present results are in line with qualitative clinical reports indicating a decrease in ruminative tendencies in patients with depression following treatment with psilocybin, 13 as well as quantitative evidence Psilocybin versus escitalopram for depression of such improvements after successful SSRI treatment for depression. 21 That rumination at week 6 improved in both conditions, in line with response, could imply that it is a central feature of depression that is sensitive to response to treatment, irrespective of the action of that treatment. ...
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Background Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression. Aims To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder. Method Based on data derived from a randomised clinical trial ( N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction. Results A time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight. Conclusions These data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.
... Only two out of six studies that administered different doses of psilocybin reported on adverse effect per dosage (Davis et al., 2020;Griffiths et al., 2016); one study described the timing of AEs per session (Carhart-Harris et al., 2016). Qualitative studies described treatment experiences among patients with EOLA Malone et al., 2018;Swift et al., 2017), TRD (Kaelen et al., 2018;Watts et al., 2017), and substance use disorder (SUD; Bogenschutz et al., 2018;Nielson et al., 2018;Noorani et al., 2018). ...
... In one RCT, patients reported moderate to strong emotional and psychological AEs, with patients endorsing statements such as "I felt like crying," sadness, emotional and/or physical suffering, feelings of grief, and feelings of isolation (Davis et al., 2020). One participant experienced confusing traumatic memories, in which a parent held a pillow over his face, which worsened his depression for several weeks post-treatment Watts et al., 2017); another patient became incommunicative during the psilocybin session . Two qualitative studies illustrated experiences from a patient perspective: I worried that I let [the music] shape this sort of melancholy. ...
... It was a process of unblocking. (Watts et al., 2017) Post-treatment headache was the only reported late AE; the openlabel study only reported headaches in the high-dose (25 mg) group. In one study, 67% rated one of the psilocybin sessions among their top five most psychologically challenging experiences (with 30% rating it the single most psychologically challenging experience (Davis et al., 2020); this was not asked in the other studies . ...
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Introduction Small-scale clinical studies with psychedelic drugs have shown promising results for the treatment of several mental disorders. Before psychedelics become registered medicines, it is important to know the full range of adverse events (AEs) for making balanced treatment decisions. Objective To systematically review the presence of AEs during and after administration of serotonergic psychedelics and 3,4-methyenedioxymethamphetamine (MDMA) in clinical studies. Methods We systematically searched PubMed, PsycINFO, Embase, and ClinicalTrials.gov for clinical trials with psychedelics since 2000 describing the results of quantitative and qualitative studies. Results We included 44 articles (34 quantitative + 10 qualitative), describing treatments with MDMA and serotonergic psychedelics (psilocybin, lysergic acid diethylamide, and ayahuasca) in 598 unique patients. In many studies, AEs were not systematically assessed. Despite this limitation, treatments seemed to be overall well tolerated. Nausea, headaches, and anxiety were commonly reported acute AEs across diagnoses and compounds. Late AEs included headaches (psilocybin, MDMA), fatigue, low mood, and anxiety (MDMA). One serious AE occurred during MDMA administration (increase in premature ventricular contractions requiring brief hospitalization); no other AEs required medical intervention. Qualitative studies suggested that psychologically challenging experiences may also be therapeutically beneficial. Except for ayahuasca, a large proportion of patients had prior experience with psychedelic drugs before entering studies. Conclusions AEs are poorly defined in the context of psychedelic treatments and are probably underreported in the literature due to study design (lack of systematic assessment of AEs) and sample selection. Acute challenging experiences may be therapeutically meaningful, but a better understanding of AEs in the context of psychedelic treatments requires systematic and detailed reporting.
... Extended author information available on the last page of the article The psychological concept of felt connection or 'connectedness' 1 has been discussed previously in the context of psychedelic therapy (Thomas et al. 2013;Watts et al. 2017;Yaden et al. 2017), but has not yet been clearly defined. Participant accounts of psychedelic therapy often include reference to an increased sense of connectedness with one's own senses, body and emotions; to friends, family and community; and to nature, the living world, global humanity, purpose and meaning. ...
... This generalised connected state was reported as feeling most intense in the weeks to months after psilocybin therapy and occurred alongside a temporary reduction in depression scores . Witnessing this association gave rise to the hypothesis that depression can be linked to a fundamental, multidimensional and generalised sense of disconnectedness and that psychedelic therapy (and other interventions) can bring about an increase in this generalised connectedness Watts et al. 2017). ...
... Connectedness to ourselves as part of an inter-related web of life may be essential to the survival of our species (Arce and Winkelman 2021), and this appears to be a common insight occurring during psychedelic therapy, as many quotes from participants in psychedelic research studies attest (Agin-Liebes et al. 2021;Andros Aronovich 2019;Belser et al. 2017;Watts et al. 2017). Such insights are often reported to lead to pro-environmental behaviours (Forstmann and Sagioglou 2017). ...
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Rationale A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ as ‘a state of feeling connected to self, others and the wider world’. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as ‘social connectedness’ or ‘nature connectedness’, which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to ‘self’, ‘others’ and ‘world’ and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use. Objectives To validate and test the ‘Watts Connectedness Scale’ (WCS). Methods Psychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint. Results As hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p < 0.0001), as well as on each of its subscales (p < 0.0001). Acute measures of ‘mystical experience’, ‘emotional breakthrough’, and ‘communitas’ correlated positively with post-psychedelic changes in connectedness (r = 0.42, r = 0.38, r = 0.42, respectively, p < 0.0001). In the RCT, psilocybin therapy was associated with greater increases in WCS scores compared with the escitalopram arm (ηp2 = 0.133, p = 0.009). Conclusions The WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research.
... Four studies reported that psilocybinassisted therapy reduces depression symptoms in patients with treatment-resistant depression (TRD) and in cancer patients (see meta-analysis Galvão-Coelho et al. 2021). Across all four studies, depression remission rates remained high (60-80%) at 3-or 6-month follow-up and patients reported being less pessimistic about their future (Watts et al. 2017). In follow-up qualitative interviews from one study (Watts et al. 2017), participants reported post-treatment shifts from avoiding traumatic memories and painful emotions to confronting and accepting them, increased understanding and compassion for past abusers, access to a fuller range of autobiographical material, and a sense of reconnection with self, others, and the world. ...
... Across all four studies, depression remission rates remained high (60-80%) at 3-or 6-month follow-up and patients reported being less pessimistic about their future (Watts et al. 2017). In follow-up qualitative interviews from one study (Watts et al. 2017), participants reported post-treatment shifts from avoiding traumatic memories and painful emotions to confronting and accepting them, increased understanding and compassion for past abusers, access to a fuller range of autobiographical material, and a sense of reconnection with self, others, and the world. In the three studies in cancer patients, psilocybin reduced trait anxiety related to having a lifethreatening illness and some participants discussed unearthing and processing childhood traumas that were realized to be unhealed (Malone et al. 2018). ...
... Similarly, in a clinical trial of ayahuasca for TRD, 76% of participants had a cluster B personality disorder, but no data on personality disorder changes were reported (Palhano-Fontes et al. 2019). Of most relevance to BPD, two studies show psilocybin reduces anxious attachment and rejection sensitivity (Stauffer et al. 2020;Preller et al. 2015) and another study found psilocybin helped people re-connect with close others who had wronged them (Watts et al. 2017). Psilocybin also increases feelings of empathy, and trait openness while decreasing trait neuroticism Roseman et al. 2018). ...
Chapter
Posttraumatic stress disorder (PTSD) is a debilitating, chronic disorder and efficacy rates of current PTSD treatments are underwhelming. There is a critical need for innovative approaches. We provide an overview of trauma and PTSD and cite literature providing converging evidence of the therapeutic potential of psilocybin for PTSD. No study to date has investigated psilocybin or psilocybin-assisted psychotherapy (PAP) as treatments for PTSD. An open-label study in traumatized AIDS survivors found that PAP reduced PTSD symptoms, attachment anxiety, and demoralization. Several PAP trials show preliminary efficacy in facilitating confronting traumatic memories, decreasing emotional avoidance, depression, anxiety, pessimism, and disconnection from others, and increasing acceptance, self-compassion, and forgiveness of abusers, all of which are relevant to PTSD recovery. There is also early evidence that other classic psychedelics may produce large reductions in PTSD symptoms in combat veterans. However, this body of literature is small, mechanisms are not yet well understood, and the risks of using psychedelic compounds for trauma-related disorders need further study. In sum, evidence supports further investigation of PAP as a radically new approach for treating PTSD.
... Promisingly, meditation practices are being integrated into psychedelic-assisted therapy trials , and related qualitative reports indicate that 'acceptance' and 'connection' are key therapeutic change processes involved in psychedelic-assisted therapy (Watts, Day, Krzanowski, Nutt, & Carhart-Harris, 2017). Though it remains unclear how psychedelics and meditative practices may interact, it is increasingly apparent that the two states of consciousness may be combined with potentially beneficial effects. ...
... Accordingly, acceptance may predict the benefits resulting from mindfulness-based therapy (Baer, Smith, Hopkins et al., 2006), and spontaneous enhancements in acceptance have been demonstrated as a result of psychedelic consumption without any meditation element (Soler et al., 2018. Acceptance has also been highlighted as a key change-process in previous qualitative work in those partaking in psilocybin-assisted therapy for treatment resistant depression (Watts et al., 2017), alongside connection. ...
... reported after consumption of psychedelics (e.g. Bouso et al., 2012;Watts et al., 2017). Nonavoidance may support both the maintenance of the mindful state (in so that one is less likely to withdraw from the experience), as well as help in 'deepening' or enhancing the quality of the experience (such that participants are more likely to face and accept challenging experiences rather than turn away or avoid them, Guss, Krause, & Sloshower, 2020). ...
Thesis
Background: Mindfulness protocols, though beneficial for a range of indications, often involve long-term commitment and may not be accessible for those naturally low in trait mindfulness (e.g. attention-/ anxiety-related disorders). It remains unclear which ‘dose’ of mindfulness is necessary to produce beneficial effects, and broadly, how drugs such as nootropics and psychedelics may interact with mindfulness meditation. / Aims: The aims of this thesis are (1) to explore what dose of mindfulness is necessary to enhance state mindfulness (among other outcomes) and whether a drug can modulate, or add to the effects of a mindfulness strategy, (2) to explore how psychedelics may affect a meditation experience, and (3) to examine what role changes in mindfulness play in regards to beneficial psychological health outcomes shown after ceremonial psychedelic use. / Methods: A mixture of methodologies were applied to answer the above questions. Specifically, single-session mindfulness literature was systematically reviewed, and a double-placebo controlled study was designed and conducted to explore the potential for pharmacological enhancement of a single mindfulness strategy. A thematic analysis was conducted to explore user accounts of combined psychedelic and meditation experiences. Finally, linear multilevel models and longitudinal mediation models were used to explore the associations between changes in mindfulness capacity and psychological health over the course of a naturalistic ayahuasca study. / Results: Single-session mindfulness studies are capable of producing a variety of beneficial effects, and adjunctive modafinil appears to enhance some effects of behavioural strategies as well as participant engagement in subsequent practice. Psychedelics may also prove to be useful counterparts to meditations, and conversely, while psychedelics appear to enhance mindfulness, meditation practice can assist also in the navigation of, and potentially enhance effects of the psychedelic process.
... Therapeutic outcomes in PAP are likely to result from a participant's engagement with many facets of themselves and their illness during treatment (Kelly et al., 2021;Thal et al., 2021;Miceli McMillan and Jordens, 2022). Medicine sessions can foster a broad range of experiences that inspire participants to make beneficial meaning of their treatment in an equally broad range of ways that include spiritual, existential, emotional, relational, cognitive, or embodied dimensions (Masters and Houston, 1966;Belser et al., 2017;Watts et al., 2017;Malone et al., 2018;Michael et al., 2021). The inclusion of a nonpsychedelic EBT that was not developed with this breadth in mind may burden the treatment with an overly narrow frame for conceptualizing benefit. ...
... Most PAP models to date have paid little attention to the role of embodied events in therapeutic outcomes, despite their prevalence in participants' accounts of their medicine experiences Watts et al., 2017). This inattention may reflect the ongoing effort to characterize PAP within the institutional bounds of Western psychiatry and psychology, which attend more exclusively to cognitive and neural phenomena. ...
... Several qualitative studies of PAP participant experiences Watts et al., 2017;Bogenschutz et al., 2018) include accounts of unprompted somatic phenomena that arose in PAP medicine sessions and were experienced by participants as important to their treatment. They included interoceptive experiences of locating undesirable psychic content (e.g., grief, shame, resentment, anger) or physical illness (e.g., cancer, sequelae of problem drinking) in their lived experience of their bodies, as well as "purgative, " "purifying, " (Watts et al., 2017, p. 550) or "washing" (Belser et al., 2017, p. 370) experiences that diminished the perceived personal impact of these maladies, sometimes by way of vomiting or spitting . ...
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The current standard of care in most uses of psychedelic medicines for the treatment of psychiatric indications includes the provision of a supportive therapeutic context before, during, and after drug administration. A diversity of psychedelic-assisted psychotherapy (PAP) models has been created to meet this need. The current article briefly reviews the strengths and limitations of these models, which are divided into basic support models and EBT-inclusive therapy models. It then discusses several shortcomings both types of models share, including a lack of adequate attention to embodied and relational elements of treatment, and insufficient attention to ethical concerns. The article then introduces the EMBARK model, a transdiagnostic, trans-drug framework for the provision of supportive psychotherapy in PAP clinical trials and the training of study therapists. EMBARK was designed to overcome challenges that prior models have had in conceptualizing therapeutic change in psychedelic treatment, incorporating elements of non-psychedelic evidence-based therapies, incorporating therapists’ prior skills and clinical orientations, delimiting therapist interventions for research standardization, and determining specific factors that contribute to treatment outcomes. The article explains EMBARK’s six clinical domains, which represent parallel conceptualizations of how therapists may support therapeutic benefit in PAP treatment, and its four care cornerstones, which reflect therapists’ broad ethical responsibility to participants. The article describes how these elements of the model come together to structure and inform therapeutic interventions during preparation, medicine, and integration sessions. Additionally, the article will discuss how EMBARK therapist training is organized and conducted. Finally, it will demonstrate the broad applicability of EMBARK by describing several current and upcoming PAP clinical trials that have adopted it as the therapeutic frame.
... Acquiring insights into oneself, heightened self-awareness and a greater insight into one's relationship with others are commonly cited by participants with anxiety and depression (Breeksema et al., 2020). Participants with treatment-resistant depression described a narrative of transformation from a presession 'disconnection' (from self, others and the world) to a renewed sense of 'connectedness' (to close family and friends, and all humanity) after psilocybin dosing (Belser et al., 2017;Watts et al., 2017). In the same cohort, participants reported gaining a fresh perspective on their lives, with increased self-compassion, an improved sense of self-worth, and a transition from emotional avoidance to acceptance (Watts et al., 2017). ...
... Participants with treatment-resistant depression described a narrative of transformation from a presession 'disconnection' (from self, others and the world) to a renewed sense of 'connectedness' (to close family and friends, and all humanity) after psilocybin dosing (Belser et al., 2017;Watts et al., 2017). In the same cohort, participants reported gaining a fresh perspective on their lives, with increased self-compassion, an improved sense of self-worth, and a transition from emotional avoidance to acceptance (Watts et al., 2017). This sense of openness and acceptance was reported to persist for months in some participants (Watts et al., 2017). ...
... In the same cohort, participants reported gaining a fresh perspective on their lives, with increased self-compassion, an improved sense of self-worth, and a transition from emotional avoidance to acceptance (Watts et al., 2017). This sense of openness and acceptance was reported to persist for months in some participants (Watts et al., 2017). Increased selfcompassion and self-acceptance have also been reported in psychedelic trials of participants with cancer and alcohol use disorder (Bogenschutz et al., 2018;Malone et al., 2018). ...
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Background Postpartum depression (PPD) is a major public health concern and has, at its core, a sense of maternal ‘disconnection’ – from the self, the infant, and the support system. While PPD bears similarities with MDD, there is increasing evidence for its distinct nature, especially with the unique aspect of the mother-infant relationship. Current treatment modalities for PPD, largely based on those used in major depressive disorder (MDD), have low remission rates with emerging evidence for treatment resistance. It is, therefore, necessary to explore alternative avenues of treatment for PPD. Objective In this narrative review, we outline the potential therapeutic rationale for serotonergic psychedelics in the treatment of PPD, and highlight safety and pragmatic considerations for the use of psychedelics in the postpartum period. Methods We examined the available evidence for the treatment of PPD and the evidence for psychedelics in the treatment of MDD. We explored safety considerations in the use of psychedelics in the postpartum period. Results There is increasing evidence for safety, and encouraging signals for efficacy, of psilocybin in the treatment of MDD. Psilocybin has been shown to catalyse a sense of ‘reconnection’ in participants with MDD. This effect in PPD, by fostering a sense of ‘reconnection’ for the mother, may allow for improved mood and maternal sensitivity towards the infant, which can positively impact maternal role gratification and the mother-infant relationship. Conclusion Psychedelic assisted therapy in PPD may have a positive effect on the mother-infant dyad and warrants further examination.
... In trying to understand the relationship between inflammation and depressive symptomology, previous work has found that inflammatory-induced feelings of social withdrawal mediate increases in depressive mood during an inflammatory challenge [71]. Interestingly, it has been repeatedly found that a single administration of a psychedelic drug, like psilocybin, lysergic acid diethylamide (LSD), ayahuasca, or the mixed 5HT2A agonist/ monoaminergic releaser 3,4methylenedioxymethamphetamine (MDMA) induces prosocial effects and increases in feelings of connectedness in both healthy participants (for a review see Preller and Vollenweider [81]) and patients [82]. These psychedelic-induced prosocial effects have been repeatedly found to relate to persisting (therapeutic) outcomes [82][83][84]. ...
... Interestingly, it has been repeatedly found that a single administration of a psychedelic drug, like psilocybin, lysergic acid diethylamide (LSD), ayahuasca, or the mixed 5HT2A agonist/ monoaminergic releaser 3,4methylenedioxymethamphetamine (MDMA) induces prosocial effects and increases in feelings of connectedness in both healthy participants (for a review see Preller and Vollenweider [81]) and patients [82]. These psychedelic-induced prosocial effects have been repeatedly found to relate to persisting (therapeutic) outcomes [82][83][84]. Finally, the only other study to-date which assessed the relationship between inflammatory markers and persisting psychological effects after psychedelic administration, found that the larger the reduction of CRP, the lower the ratings of depression 48 hours after ayahuasca treatment [16]. ...
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Patients characterized by stress-related disorders such as depression display elevated circulating concentrations of pro-inflammatory cytokines and a hyperactive HPA axis. Psychedelics are demonstrating promising results in treatment of such disorders, however the mechanisms of their therapeutic effects are still unknown. To date the evidence of acute and persisting effects of psychedelics on immune functioning, HPA axis activity in response to stress, and associated psychological outcomes is preliminary. To address this, we conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n=30) or 0.17 mg/kg psilocybin (n=30). Blood samples were taken to assess acute changes in immune status, and 7 days after drug administration. Seven days post-administration, participants in each treatment group were further subdivided: 15 underwent a stress induction protocol, and 15 underwent a control protocol. Ultra-high field magnetic resonance spectroscopy was used to assess whether acute changes in glutamate or glial activity were associated with changes in immune functioning. Finally, questionnaires assessed persisting self-report changes in mood and social behavior. Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a), while other inflammatory markers (interleukin (IL)-1a, IL-1b, IL-6, and C-reactive protein (CRP)) remained unchanged. Seven days later, TNF-a concentrations returned to baseline, while IL-6 and CRP concentrations were persistently reduced in the psilocybin group. Changes in the immune profile were related to acute neurometabolic activity as acute reductions in TNF-a were linked to lower concentrations of glutamate in the hippocampus. Additionally, the more of a reduction in IL-6 and CRP seven days after psilocybin, the more persisting positive mood and social effects participants reported. Regarding the stress response, after a psychosocial stressor, psilocybin blunted the cortisol response compared to placebo. Such acute and persisting changes may contribute to the psychological and therapeutic effects of psilocybin demonstrated in ongoing patient trials.
... This can help PTSD patients as they frequently exhibit increased amygdala activation [40]. They may also play a therapeutic role in the management of PTSD by virtue of other acute effects, such as higher levels of emotional empathy [41], increased insightfulness [42], improvements in acceptance [43], and emotive transformational events, which has shown to be a key mediator in the long-term psychological change in other mental disorders [44]. So far, no clinical trials have been conducted to examine the potential of classical psychedelics for the treatment of PTSD [4]. ...
... They also cause mentally challenging experiences, such as anxiety and confusion [45]. Some patients may exhibit emotional vulnerability in the days after the therapy, which emphasizes the significance of receiving psychological assistance [43]. Classical psychedelics can cause an increase in heart rate and blood pressure. ...
Article
Post-traumatic stress disorder (PTSD) is a significant public health concern for which existing therapies are only marginally effective. Indisputably, the primary line of treatment for PTSD is psychotherapy, according to current treatment guidelines. However, PTSD continues to be a chronic condition even after psychotherapy, with high psychiatric and medical illness rates. There is a dire need to search for new compounds and approaches for managing PTSD. The usage of psychedelic substances is a potential new method. This article reviews the efficacy of psychedelic-assisted therapy in treating PTSD and improving patient outcomes. It will examine current research on the topic and evaluate the benefits and drawbacks of different therapies. The current evidence for the use of four different types of psychedelics (3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics, and cannabis) in the treatment of PTSD will be reviewed. It will also include an overview of the therapeutic justification, context of use, and level of evidence available for each drug. Several questions are formulated that could be studied in future research in order to gain a better understanding of the topic.
... Qualitatively, psychedelics have been shown to enhance connection to self and others as well as acceptance of difficult emotions (Watts et al., 2017). Patients receiving conventional therapy, on the other hand, sometimes report feeling disconnected from self and others and a tendency to avoid difficult emotions (Watts et al., 2017). ...
... Qualitatively, psychedelics have been shown to enhance connection to self and others as well as acceptance of difficult emotions (Watts et al., 2017). Patients receiving conventional therapy, on the other hand, sometimes report feeling disconnected from self and others and a tendency to avoid difficult emotions (Watts et al., 2017). Despite not showing a statistically significant difference in a recent head-to-head comparison of psilocybin versus escitalopram for depression, the remission rate at the six-week follow-up was 57 % in the psilocybin group compared to 28 % in the escitalopram group . ...
Article
Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional, social, and self-referential information. The use of animal behavior to study psychedelics is under debate, and this review provides a critical perspective on the translational value of animal behavior studies in psychedelic research. Acute activation of 5-HT2ARs produces head twitches and unique discriminative cues, disrupts sensorimotor gating, and stimulates motor activity while inhibiting exploration in rodents. The acute treatment with psychedelics shows discrepant results in conventional rodent tests of depression-like behaviors but generally induces anxiolytic-like effects and inhibits repetitive behavior in rodents. Psychedelics impair waiting impulsivity but show discrepant effects in other tests of cognitive function. Tests of social interaction also show conflicting results. Effects on measures of time perception depend on the experimental schedule. Lasting or delayed effects of psychedelics in rodent tests related to different behavioral domains appear to be rather sensitive to changes in experimental protocols. Studying the effects of psychedelics on animal behaviors of relevance to effects on psychiatric symptoms in humans, assessing lasting effects, publishing negative findings, and relating behaviors in rodents and humans to other more translatable readouts, such as neuroplastic changes, will improve the translational value of animal behavioral studies in psychedelic research. SIGNIFICANCE STATEMENT: Psychedelics like LSD and psilocybin have received immense interest as potential new treatments of psychiatric disorders. Psychedelics change high-order consciousness in humans, and there is debate about the use of animal behavior studies to investigate these compounds. This review provides an overview of the behavioral effects of 5-HT2AR agonist psychedelics in laboratory animals and discusses the translatability of the effects in animals to effects in humans. Possible ways to improve the utility of animal behavior in psychedelic research are discussed.
... High ratings for CE have been associated with both worsened Carbonaro et al., 2016;Haijen et al., 2018;Roseman et al., 2018) and improved long-term mental health outcomes (Carbonaro et al., 2016;Davis et al., 2021b). These contradictory findings are likely explainable by whether a period of psychological challenge results in a psychological insightful therapeutic breakthrough or not Carbonaro et al., 2016;Davis et al., 2020;Roseman et al., 2018;Watts et al., 2017). ...
... These trials were of a period prior to the establishment of validated measures and quantitative response criteria, but more recent experimental and cross-sectional studies have lent support to the merits of psychedelic therapy for depression, with two notable recent controlled trials finding response rates exceeding 70% (Carhart-Harris et al., 2021a;Davis et al., 2021a). These trials supplement a number of lab-based experimental studies conducted in the last 10 years that have found consistent positive results in favour of the therapeutic potential of psychedelic therapy for treating symptoms of depression and anxiety (Carhart-Harris et al., 2016a, 2017Davis, Barrett and May, 2021;Gasser et al., 2014;Grob et al., 2011;Griffiths et al., 2016;Osório et al., 2015;Ross et al., 2016;Sanches et al., 2016;Watts et al., 2017). Specifically, controlled trials involving both inert and active comparators, such as first-line standard of care (an SSRI course) plus psychological support in one recent trial (Carhart-Harris et al., 2021a), serve to highlight the robust and reliable antidepressant and anxiolytic effects of psychedelic therapy. ...
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Background Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Aim Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Method Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. Results Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. Conclusion These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.
... Their antidepressant effects appear to be notably more rapid and long-lasting compared to traditional antidepressant medications. 8 Additionally, psychedelics appear to effectively alleviate depressive symptoms while also providing depressed patients with unique and adaptive psychological benefits, including increased cognitive flexibility, 9 mindfulness, 9 psychological flexibility, 10 acceptance, 11 connectedness, 11 and catharsis. 12 One clinical trial 13 implied that these unique effects may be exclusive to psychedelics, in that they are not commonly found with classical antidepressant medications. ...
... Their antidepressant effects appear to be notably more rapid and long-lasting compared to traditional antidepressant medications. 8 Additionally, psychedelics appear to effectively alleviate depressive symptoms while also providing depressed patients with unique and adaptive psychological benefits, including increased cognitive flexibility, 9 mindfulness, 9 psychological flexibility, 10 acceptance, 11 connectedness, 11 and catharsis. 12 One clinical trial 13 implied that these unique effects may be exclusive to psychedelics, in that they are not commonly found with classical antidepressant medications. ...
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Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from subjective outcomesTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.
... A noteworthy extra-pharmacological factor in our study, and some of the previously mentioned studies (22,86), is the consumption of a psychedelic drug in a group context. Psychedelic drugs have been found to modulate social cognition and interpersonal experiences (87), and individuals whom have undergone psychedelic therapy with psychological support have indicated that increased feelings of social connectedness were an important aspect of the therapeutic process (88). Thus taking together the aforementioned reports, as well as reports from historical research with psychedelic-assisted group therapy [see (89), for a review], it could be hypothesized that the incorporation of groups into psychedelic-assisted psychotherapy may enhance therapeutic outcomes (89). ...
... That said, it has yet to be systematically assessed whether such a "peak" experience is necessary for long-term outcomes (95), or whether the subjective experiences elicited by psychedelic substances are merely epiphenomena of the underlying neurobiological mechanisms, the latter which are conveying any beneficial effects. Additionally, it is possible that other psychological components play important roles in mediating long-term outcomes of psychedelic experience, for instance insight/breakthrough or catharsis, suggestibility, and reliving of trauma have been suggested as important factors determining the psychedelic experience (15,88,(96)(97)(98)(99)(100). Therefore, we should remain cautious when developing and interpreting specific theoretical frameworks of psychedelics' (psychological) mechanisms of action and focus future efforts on testing these frameworks in the context of experimental studies. ...
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Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in deficient treatment responses. Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and 1 week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males = 25; females = 25; others = 2) completed parts of the baseline assessment, 46 (males = 21; females = 24; others = 1) completed assessments the morning after the ceremony, and 23 (males = 10; females = 13) completed assessments at the 1-week follow-up. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, we observed medium reductions in anxiety measures (both state and trait) compared to baseline (d¯ = 6.4; p < 0.001 and d¯ = 6; p = 0.014, respectively), which persisted over a 1-week period post-ceremony (d¯ = 6.7; p = 0.001 and d¯ = 8.6; p = 0.004, respectively). At 1 week post-ceremony, the non-judging facet of the mindfulness scale was increased (d¯ = 1.5; p = 0.03), while the personality trait neuroticism decreased (d¯ = 5.2; p = 0.005), when compared to baseline. Additionally, we found ratings of ego dissolution (mean: 59.7, SD: 28.3) and changes in neuroticism to be the strongest predictors of reductions in state and trait anxiety, respectively. In sum, results suggest rapid and persisting (up to 1 week) anxiolytic effects in individuals with sub-clinical anxiety symptoms, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. Results also add support to the feasibility and potential efficacy of group sessions with psychedelics. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.
... psilocybin, the psychedelic prodrug in magic mushrooms) are also identified as being the most semantically similar to NDEs . In terms of sustained changes, similarly to the near-death experience, psilocybin has been evidenced to exert significant and sustained alleviation of death-anxiety in the terminally ill (Agin-Liebes et al., 2020), as well as depression for instance via subjective effects of increased connection to others (Watts et al., 2017). DMT use is shown to radically undermine one's prior atheistic beliefs (Davis, Clifton, et al., 2020), and psychedelics are illustrated as catalysing nature-relatedness (Kettner et al., 2019). ...
... This is, of course, taking the assumption that it is the distinct experience of the NDE which primarily mediates the subsequent therapeutic effects, beside more implicitly cognitive of neurobiological effects. This is substantiated by a wealth of studies for both psychedelic therapy, for instance through increased connection, mystical experience and emotional breakthrough (Watts et al, 2017;Ross et al, 2016;Roseman et al., 2019;Kaertner et al., 2021), and near-death experiences, for instance improving attitudes towards death and spiritual wellbeing (Greyson, 1992(Greyson, , 1993Khanna & Greyson, 2013;Greyson & Khanna, 2014). ...
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The near-death experience (NDE) is an example of an extraordinary human experience which also confers a pattern of positive psychospiritual after-effects. Both its phenomenological features and long-term changes are very comparably identified after experiences with classical psychedelic drugs, which are now surfing a new wave of intense research attention. Both experience types are overwhelmingly positive in such after-effects, yet in the minority of cases of challenging experiences they may also have deleterious outcomes. Psychedelic-assisted psychotherapy provides preparational and integrational sessions around the experience, which should be precisely mirrored for near-death experiencers, so as not only to maximise psychospiritual benefit, but minimise the potential for harm. In addition to this, the NDE is arguably a more potent inducer of transformation, and as such clinical psychedelic work could be optimised by as closely simulating the NDE as possible. This is a pre-publication version of the following article: Michael, P. (2022). Thanatotherapy: How Psychedelic-assisted Psychotherapy and the Near-death Experience can Mutually Benefit One Another. Psychotherapy Section Review, 67, 99–108.
... Help the client be more open to new patterns of behavior which are not organized around avoidance and escape; cultivate openness and acceptance Acceptance has been proposed by previous authors as one process through which psychedelics may have their effects (Watts et al., 2017). Practice with this orientation may be useful during session as well. ...
... In preparation sessions, it may be advantageous to cultivate this openness to acceptance and the idea that attempting to control thoughts and feelings often creates suffering. This seems especially relevant to psychedelic psychotherapy as acceptance has been proposed by previous authors as one process through which psychedelics may have their effects (Watts et al., 2017) and thus an explicit focus on fostering and supporting this process may fit particularly well with the psychedelic experience. ...
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The acute subjective effects of psychedelics are responsive to users’ expectations and surroundings (i.e., “set and setting”). Accordingly, a great deal of thought has gone into designing the psychosocial context of psychedelic administration in clinical settings. But what theoretical paradigms inform these considerations about set and setting? Here, we describe several historical, sociological influences on current psychedelic administration in mainstream European and American clinical research settings, including: indigenous practices, new age spirituality from the 1960s, psychodynamic/psychoanalytic approaches, and cognitive-behavioral approaches. We consider each of these paradigms and determine that cognitive-behavioral therapies, including newer branches such as acceptance and commitment therapy (ACT), have the strongest rationale for psychedelic-assisted psychotherapy going forward. Our primary reasons for advocating for cognitive-behavioral approaches include, (1) they avoid issues of cultural insensitivity, (2) they make minimal speculative assumptions about the nature of the mind and reality, (3) they have the largest base of empirical support for their safety and effectiveness outside of psychedelic therapy. We then propose several concepts from cognitive-behavioral therapies such as CBT, DBT, and ACT that can usefully inform the preparation, session, and integration phases of psychedelic psychotherapy. Overall, while there are many sources from which psychedelic psychotherapy could draw, we argue that current gold-standard, evidence-based psychotherapeutic paradigms provide the best starting point in terms of safety and efficacy.
... At a more basic psychological level, the potent thoughts, feelings, and memories that emerge during a psychedelic experience may provide an opportunity to form both new insights and new ways of relating to and responding to inner experience. For instance, patients may learn a process of awareness, acceptance, approach, and "letting go" of emotions to replace a rigid emphasis on controlling, suppressing, or avoiding them (Watts, Day, Krzanowski, Nutt, & Carhart-Harris, 2017). Emotion regulation difficulties are associated with OCD (Berman, Shaw, & Wilhelm, 2018;Khosravani, et al., 2020a;Khosravani, et al., 2020b;Stern, et al., 2014;Yap, et al., 2018), so an important part of treatment may be to help people with OCD better process and respond to their emotions. ...
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Classic psychedelics, such as psilocybin, act on the brain’s serotonin system and produce striking psychological effects. Early work in the 1950s and 1960s and more recent controlled studies suggest benefit from psychedelic treatment in a number of conditions. A few case reports in recreational users and a single experimental study suggest benefit in patients with obsessive-compulsive disorder (OCD), but careful clinical data and long-term follow-up have been lacking. Here we describe a case of a patient with refractory OCD treated with psilocybin and followed prospectively for a year, with marked symptomatic improvement. We provide qualitative and quantitative detail of his experience during and after treatment. Improvement in OCD symptoms (YBOCS declined from 24 to 0-2) was accompanied by broader changes in his relationship to his emotions, social and work function, and quality of life. This individual was an early participant in an ongoing controlled study of psilocybin in the treatment of OCD (NCT03356483). These results are preliminary but promising, motivating ongoing investigations of the therapeutic potential of appropriately monitored and supported psychedelic treatment in the treatment of patients with obsessions and compulsions.
... 5 For instance, one qualitative analysis revealed that many participants in a clinical trial reported spontaneous health behavior changes following administration of psilocybin. 6 Other studies with cross-sectional research designs indicate that lifetime classic psychedelic use may be associated with positive health behavior related to alcohol, tobacco, diet, and exercise, 7,8 but such links have not yet been examined in nationally representative samples free of significant self-selection bias. ...
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Background Preliminary evidence suggests that classic psychedelics may be effective in the treatment of some psychiatric disorders, yet little remains known about their effects on health behavior and physical health. Objectives The purpose of this study was to investigate associations of lifetime classic psychedelic use and psychological insight during one’s most insightful classic psychedelic experience with health behavior and physical health. Methods Using data representative of the US population with regard to sex, age, and ethnicity ( N = 2822), this study examined associations of lifetime classic psychedelic use and psychological insight with health behavior and physical health. Results Lifetime classic psychedelic use was associated with more healthy tobacco-related and diet-related behavior ( β = 0.05 and 0.09, respectively). Among lifetime classic psychedelic users ( n = 613), greater Psychological Insight Questionnaire (PIQ) total scale, PIQ Avoidance and Maladaptive Patterns (AMP) subscale, and PIQ Goals and Adaptive Patterns (GAP) subscale scores were each associated with higher odds of more healthy exercise-related behavior [adjusted odds ratios (aOR) (95% confidence interval, CI = 1.38 (1.13–1.68), 1.38 (1.13–1.68), and 1.32 (1.10–1.60), respectively] and higher odds of having a healthy body mass index (BMI) [aOR (95% CI) = 1.32 (1.07–1.63), 1.36 (1.10–1.69), and 1.23 (1.01–1.50), respectively], and greater GAP subscale scores were associated with more healthy diet-related behavior ( β = 0.10). All PIQ scales were positively associated with some health behavior improvements (overall, diet, exercise) attributed to respondents’ most insightful classic psychedelic experience ( β = 0.42, 0.18, and 0.17; β = 0.40, 0.19, and 0.17; and β = 0.40, 0.15, and 0.15, respectively), but only PIQ total scale and AMP subscale scores were positively associated with alcohol-related health behavior improvements ( β = 0.13 and 0.16, respectively). Conclusion Although these results cannot demonstrate causality, they suggest that psychological insight during a classic psychedelic experience may lead to positive health behavior change and better physical health in some domains, in particular in those related to weight management.
... Recent years have seen renewed interest in the use of psychedelic substances for treating various psychiatric conditions. Psilocybin has been most extensively studied, with small-scale academic studies reporting efficacy for depression and anxiety (1)(2)(3)(4)(5)(6)(7)(8)(9), and substance use disorders (10)(11)(12)(13)(14). Despite these promising results, a challenge facing the clinical uptake of psilocybin and other agents with protracted acute psychedelic effects is the amount of time and clinical resources a well conducted therapy session entails (15). ...
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Background The psychedelic 5-MeO-DMT has shown clinical potential due to its short duration and ability to induce mystical experiences. However, a phenomenon known as “reactivations” (similar to “flashbacks”) is a poorly understood and frequently reported phenomenon which appears associated with 5-MeO-DMT use and warranted further investigation. Aims This study examined whether differences in age, gender, education, lifetime use, use location, and preparation strategies predict reactivations (primary outcome). Additionally, we explored how reactivations were perceived by survey respondents and whether demographic data predicted emotional valence (secondary outcome) of reported reactivations. Materials and methods This study used secondary quantitative data from a survey assessing epidemiological and behavioral associations of 5-MeO-DMT use in non-clinical settings ( N = 513). Descriptive statistics, chi-square tests, t -tests, and logistic regressions were utilized to explore aims. Results Being female, older at the time of first 5-MeO-DMT dose, having higher educational attainment, and dosing in a structured group setting were associated with increased odds of reporting a reactivation event. Higher mystical experience scores, greater personal wellbeing and having had a non-dual awareness experience that was not substance-induced were associated with higher likelihood of reporting a neutral or positive emotional valence of a reactivation event. Conclusion These findings suggest that reactivation phenomena, in this particular sample may most often represent a neutral or positive byproduct of the acute 5-MeO-DMT experience. More information is needed to best identify individuals most likely to experience a reactivation as a negative event to prevent such potential challenging outcomes.
... For example, liking the presented music is reported to promote safety and companionship (Belser et al., 2017;Noorani et al., 2018) and induce a sense of being on a personal journey (Gasser et al., 2014;Belser et al., 2017;Kaelen et al., 2018). Openness to and liking the presented music also correlate with the intensity of acute psychoactive effects of psilocybin and with better antidepressant treatment outcome , perhaps by enabling depressed patients to surrender and accept repressed emotions (Watts et al., 2017). These effects are likely compounded by the fact that psychedelic drugs themselves enhance the emotional and meaning-making response to music (Kaelen et al., 2015;Preller et al., 2017). ...
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The psychedelic drug psilocybin has been successfully explored as a novel treatment for a range of psychiatric disorders. Administration of psilocybin requires careful attention to psychological support and the setting in which the drug is administered. The use of music to support the acute psychoactive effects of psilocybin is recommended in current guidelines, but descriptions of how to compile music programs for the 4–6 h long sessions are still scarce. This article describes the procedural steps and considerations behind the curation of a new music program, the Copenhagen Music Program, tailored to the intensity profile of a medium/high dose psilocybin. The method of Guided Imagery and Music is presented as a music therapeutic framework for choosing and sequencing music in music programming and the Taxonomi of Therapeutic Music is presented as a rating tool to evaluate the music-psychological intensity of music pieces. Practical examples of how to organize the process of music programming are provided along with a full description of the Copenhagen Music Program and its structure. The aim of the article is to inspire others in their endeavours to create music programs for psychedelic interventions, while proposing that an informed music choice may support the therapeutic dynamics during acute effects of psilocybin.
... In a safe and supportive setting, psychedelic drugs can cause personally meaningful, emotionally salient experiences which can lead to lasting improvements in well-being [11]. Both patients and healthy volunteers report insights into personal problems, emotional breakthroughs, reprocessing of traumatic memories, and feelings of connectedness and empathy for oneself and others [7,12,123,[153][154][155][156]. Sometimes this can take the form of a "helioscope effect" in which people seem to perceive their experiences in more detail, but are also able to work through difficult material without becoming overwhelmed [157]. ...
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Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. “microdoses”), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics’ effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics’ effects on neuroplasticity and its potential clinical applications.
... Findings from clinical research on classic psychedelics are supported by results from cross-sectional studies with nationally representative samples [37][38][39][40], but more recent cross-sectional research has also found associations between lifetime classic psychedelic use and lower odds of obesity and cardiometabolic diseases in the past year [41][42][43]. While causality has not been established, such findings could potentially be explained by healthy lifestyle changes after classic psychedelic use [44][45][46][47]. ...
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Objectives: Absenteeism from work due to illness, and related costs, has increased steadily during the past decades. In recent years, there has been a reemergence of research on the therapeutic effects of classic psychedelics showing associations with both physical and mental health. However, the association between classic psychedelics and sick leave remains unknown. The aim of this study is to investigate the association between lifetime classic psychedelic use and sick leave in the past 30 days among adults in the United States (N = 407,717), using data from the National Survey on Drug Use and Health (2005-2019), weighted to be representative of the US adult population. Methods: The primary analysis was conducted using multiple linear regression, controlling for sociodemographic characteristics, risky behavior, and use of other substances. Results: There was a significant and negative association between lifetime classic psychedelic use and sick leave in the past 30 days (B = -0.09, p < 0.01) when adjusting for all control variables. Conclusion: These findings suggest that classic psychedelics could potentially lead to reduced sick leave and associated costs in the general population, but more research is needed to investigate potential causal pathways of classic psychedelics on sick leave and evaluate possible mechanisms.
... Psychedelics reduce activation in threat-related regions of the brain-the amygdala-allowing people to ruminate less on trauma, obsessive ideas, addictions, or even the imminence of dying (Vollenweider & Preller, 2020). Psychedelics lead people to feel greater connectedness to others and the world in general (Carhart-Harris et al., 2018;Watts et al., 2017), feel fewer distinctions with others (Vollenweider & Preller, 2020), and be more altruistic (Griffiths et al., 2006)-awe-like shifts in the sense of self, relationality, and prosociality. Most directly, psychedelics can reduce depression, anxiety, and addiction through experiences of awe (Hendricks, 2018). ...
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How do experiences in nature or in spiritual contemplation or in being moved by music or with psychedelics promote mental and physical health? Our proposal in this article is awe. To make this argument, we first review recent advances in the scientific study of awe, an emotion often considered ineffable and beyond measurement. Awe engages five processes—shifts in neurophysiology, a diminished focus on the self, increased prosocial relationality, greater social integration, and a heightened sense of meaning—that benefit well-being. We then apply this model to illuminate how experiences of awe that arise in nature, spirituality, music, collective movement, and psychedelics strengthen the mind and body.
... These results are significantly different from the effect of SSRIs, which cause a decreased response in the amygdala during a similar test [42]. One hypothesis is that psilocybin, and psychedelics in general, allow for greater acceptance of both positive and negative emotions compared to SSRIs, which can cause an emotional blunting [43]. A previous study showed a decrease in right amygdala responses to emotional stimuli [44], but the test was performed during the acute phase of the effects and not at 24 h as in the study by Roseman et al. [41•]. ...
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Purpose of the Review We aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action. Recent Findings Psilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effects limited to a few hours after dosing. The studies conducted to date have had small sample sizes. One clinical trial has been conducted against a reference treatment (escitalopram) without showing a significant superiority of psilocybin in the main outcome. The neurobiological mechanisms, mostly unknown, differ from those of SSRI antidepressants. Summary Psilocybin represents a promising alternative in the treatment of depression. Further research with larger sample sizes, particularly against reference treatments, is needed to better understand the neurobiological factors of its effects and to investigate its potential for use in everyday practice.
... The empathic effect is a point of coincidence with some contemporary therapeutic proposals. Several reports indicate that psilocybin-assisted psychotherapy has enhanced effects on depression, and overall positive effects on behavior, when it involves social support and peer-to-peer dialogues that foster bonding or connection between research participants (Carhart-Harris et al. 2018;Griffiths et al. 2018;Watts et al. 2017). In this regard, psilocybin appears to have an impact on affective dimensions underlying these bonds. ...
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We present the set and setting of the velada, the Mazatec ritual of divination and healing. We highlight the subjective experiences of individuals who consumed sacred mushrooms and interpret them from their cultural and community contexts, but also from findings derived from experimental and neuroscientific research. We understand that the experiences connected to sacred mushrooms can be explained by the effects of psilocybin on the neurobiology of emotions, decision making, and visual, auditory, and bodily imagery. But we also understand that experimentation does not consider the individual and collective history of the person, and that the velada can provide guidance for integrating a person’s history and beliefs into experimental designs. The resurgence of psychedelic medicine prompts us into a transdisciplinary dialogue that encompasses both the anthropological perspective and the set and setting of the entheogenic experience during the sacred mushroom ritual.
... Psychedelics like psilocybin interfere with these relevant mechanisms by reducing negative feelings of social isolation and rejection, and potentially reinstating emotional empathy and social reward processes . After one-time administration of psilocybin, patients suffering from depression reported more positive connection to their social environment, which was reported as one of the most important factors contributing to their treatment success (Watts et al., 2017). ...
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This is a narrative review about the role of classic and two atypical psychedelics in the treatment of unipolar and bipolar depression. Since the 1990s, psychedelics experience a renaissance in biomedical research. The so-called classic psychedelics include lysergic acid diethylamide (LSD), psilocybin, mescaline and ayahuasca. Characteristic effects like alterations in sensory perception, as well as emotion- and self-processing are induced by stimulation of serotonin 2A receptors in cortical areas. The new paradigm of psychedelic-assisted psychotherapy suggests a therapeutic framework in which a safely conducted psychedelic experience is integrated into a continuous psychotherapeutic process. First randomized, controlled trials with psilocybin show promising efficacy, tolerability, and adherence in the treatment of unipolar depression. On the other hand, classic psychedelics seem to be associated with the induction of mania, which is an important issue to consider for the design of research and clinical protocols. So called atypical psychedelics are a heterogeneous group with overlapping subjective effects but different neurobiological mechanisms. Two examples of therapeutic value in psychiatry are 3,4-methyl enedioxy methamphetamine (MDMA) and ketamine. Since 2020 the ketamine enantiomer esketamine has been granted international approval for treatment-resistant unipolar depression, and also first evidence exists for the therapeutic efficacy of ketamine in bipolar depression. Whether psychedelics will fulfil current expectations and find their way into broader clinical use will depend on future rigorous clinical trials with larger sample sizes. A well-considered therapeutic and legal framework will be crucial for these substances to create new treatment settings and a potential paradigm shift.
... In recent years, psychedelic serotonin 2A receptor agonists ("classic psychedelics"), combined with psychological support, have been explored as a novel treatment model for a range of psychiatric disorders [38,39]. Although definitions vary slightly, classic psychedelics typically include psilocybin ("magic mushrooms"), N,N-dimethyltryptamine (DMT), the DMT-containing concoction ayahuasca, lysergic acid diethylamide (LSD), mescaline, and the mescaline-containing cacti peyote and San Pedro [40]. ...
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Previous research has found associations between classic psychedelic use and nature-relatedness, but the link between classic psychedelic use and human–animal relations remains largely unexplored. Using data representative of the US adult population, with regard to age, sex and ethnicity (N = 2822), this pre-registered study assessed lifetime classic psychedelic use, ego dissolution during respondents’ most intense experience using a classic psychedelic, and three measures related to human–animal relations: speciesism, animal solidarity and desire to help animals. The results showed that lifetime classic psychedelic use was negatively associated with speciesism (β = −0.07, p = 0.002), and positively associated with animal solidarity (β = 0.04, p = 0.041), but no association was found with desire to help animals (β = 0.01, p = 0.542). Ego dissolution during the respondents’ most intense experience using a classic psychedelic was negatively associated with speciesism (β = −0.17, p < 0.001), and positively associated with animal solidarity (β = 0.18, p < 0.001) and desire to help animals (β = 0.10, p = 0.007). The findings indicate that classic psychedelics and ego dissolution may have an impact on human–animal relations. As these results cannot demonstrate causality, however, future studies should use longitudinal research designs to further explore the potential causal link between classic psychedelic use and human–animal relations.
... In terms of differences, the long-term antidepressant action of SSRIs includes reduced limbic reactivity and emotional restraint or decline, likely achieved through post-synaptic 5-HT1Ar signalling (Cowen and Browning, 2015). This discriminates the superior role of 5-HT2Ar signalling in psilocybin use and emphasizes emotional release (Watts et al., 2017;Mertens et al., 2020). Different approaches to emotion may be the ultimate difference between the SSRI and psilocybin treatment models of depression and PTSD. ...
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Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.
... Although the data for the induction of mystical experiences per-se is derived from healthy volunteers, the score for Oceanic Boundlessness on the Altered States of Consciousness questionnaire obtained in one clinical trial of psilocybin for Major Depression can be used as proxy for mystical experience, and was found to have a strong positive correlation with outcome [40]. In addition, some subjects with treatment resistant depression participated in therapeutic analysis following psilocybin treatment, and increased openness and connectedness were identified as key sources of change in their lives [106]. ...
Article
Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action for 3,4-Methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin in treating PTSD, along with available clinical evidence, safety and side effects. MDMA-assisted psychotherapy is in FDA phase III clinical trials for PTSD and is purported to work by way of increased empathy and decreased amygdala activation during the therapeutic encounter and trauma processing. Classical psychedelics may create change by a subjective transformative experience along with an observable process of brain network alterations, though these substances have not been clinically studied in the context PTSD. In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile. There is not yet direct clinical evidence for classical psychedelics in treating PTSD, but the evidence supports such a trial. The studies to date have been relatively small, and participants are wellscreened for potential co-morbidities which could increase the risks of psychedelic treatment. Nonetheless, the data is promising for psychedelic-assisted treatment to become a much-needed treatment option for PTSD.
... The lockdowns, social distancing, and uncertainty that have arisen as a result of the public response to the COVID-19 pandemic have created the conditions for increased social isolation and loneliness, which are correlated with feelings of fear, anxiety, stress, depressive thoughts, and helplessness [62][63][64] . While the longer term effects of COVID remain to be determined, past studies have highlighted social disconnectedness to be a key feature of depression 65 , while feelings of connectedness are associated with reduced depressive symptoms 66 . By encouraging participants to imagine their own bodies and those of others as energetic essences whose luminosity extends beyond the boundaries of their material form, Isness-D offers participants new experiences of connectedness, which may help address the isolation resulting from COVID. ...
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With a growing body of research highlighting the therapeutic potential of experiential phenomenology which diminishes egoic identity and increases one’s sense of connectedness, there is significant interest in how to elicit such ‘self-transcendent experiences’ (STEs) in laboratory contexts. Psychedelic drugs (YDs) have proven particularly effective in this respect, producing subjective phenomenology which reliably elicits intense STEs. With virtual reality (VR) emerging as a powerful tool for constructing new perceptual environments, we describe a VR framework called ‘Isness-distributed’ (Isness-D) which harnesses the unique affordances of distributed multi-person VR to blur conventional self-other boundaries. Within Isness-D, groups of participants co-habit a shared virtual space, collectively experiencing their bodies as luminous energetic essences with diffuse spatial boundaries. It enables moments of ‘energetic coalescence’, a new class of embodied intersubjective experience where bodies can fluidly merge, enabling participants to include multiple others within their self-representation. To evaluate Isness-D, we adopted a citizen science approach, coordinating an international network of Isness-D 'nodes'. We analyzed the results (N = 58) using 4 different self-report scales previously applied to analyze subjective YD phenomenology (the inclusion of community in self scale, ego-dissolution inventory, communitas scale, and the MEQ30 mystical experience questionnaire). Despite the complexities associated with a distributed experiment like this, the Isness-D scores on all 4 scales were statistically indistinguishable from recently published YD studies, demonstrating that distributed VR can be used to design intersubjective STEs where people dissolve their sense of self in the connection to others.
... Reductions in experiential avoidance were significantly associated with decreases in depression and suicidality scores [55]. These outcomes are in line with previous reports from participants of clinical trials, who described a notable shift from emotional avoidance to acceptance, after receiving psilocybin-assisted psychotherapy for treatment-resistant depression [57]. Other prospective surveys have found psychological flexibility (a set of processes which allow one to adapt to various demands, maintain balance across various domains and be open to and committed to behaviours congruent to their values) to be negatively correlated with depression scores post psychedelic use [58,59]. ...
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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. Discussion This 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 the inclusion of limited 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 PROSPERO CRD42020197202
... 49 For example, three months after psilocybin treatment, patients showed an increase in extraversion and openness scores, 50 with some patients reporting an ability to re-connect with close relationships, including people who had wronged them. 51 There was also a significant increase in nature relatedness (subjective connection to nature), sustained up to a year after administration. 52 Participants taking part in a smoking cessation trial described engaging in prosocial and altruistic behaviours after their psilocybin sessions, 53 and psilocybin was shown to reduce altruistic punishment as rejections were reduced in the ultimatum game 54 and 'social pain signals' in the Cyberball game, suggesting that it attenuates responses to negative stimuli correlating to changes in self-processing rather than a lack of awareness of their exclusion. ...
Article
Psilocybin as a novel treatment for depression is garnering a lot of attention from both the mainstream media and the academic community. Although phase 3 trials are only just beginning, we feel that it is important for clinicians to consider what psilocybin-assisted psychotherapy might look like in the clinical setting. In this narrative review article we have considered the difficulties that may arise as psilocybin emerges from the research setting, which may hamper its progress towards becoming a licenced medication. Psilocybin has its own unique challenges: the expectation patients come to dosing with having read overwhelmingly positive media; patient suggestibility under the influence of psilocybin and requirement for specialised therapists to name a few. We have also made some recommendations for measures that should be taken in both the phase 3 trials and with clinicians to try and minimise some of the issues raised. In doing so our hope is that psilocybin will continue towards becoming a licenced medication that suitable patients are able to access with relative ease. Practicing psychiatrists need to have an awareness of the potential pitfalls of psilocybin as they will be responsible for prescribing it in the future.
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Background Ketamine and its enantiomer esketamine represent promising new treatments for treatment-resistant depression (TRD). Esketamine induces acute, transient psychoactive effects. How patients perceive esketamine treatment, and which conditions facilitate optimal outcomes, remains poorly understood. Understanding patient perspectives on these phenomena is important to identify unmet needs, which can be used to improve (es)ketamine treatments.AimsTo explore the perspectives of TRD patients participating in “off label” oral esketamine treatment.Materials and methodsIn-depth interviews were conducted with 17 patients (11 women) after a six-week, twice-weekly esketamine treatment program, and subsequently after six months of at-home use. Interviews explored participants’ perspectives, expectations, and experiences with esketamine treatment. Audio interviews were transcribed verbatim and analysed following an Interpretative Phenomenological Analysis (IPA) framework.ResultsKey themes included overwhelming experiences; inadequate preparation; letting go of control; mood states influencing session experiences; presence and emotional support, and supportive settings. Patients’ attempts to let go and give into vs. attempts to maintain control over occasionally overwhelming experiences was a central theme. Multiple factors influenced patients’ ability to give into the experience and appeared to impact their mood and anxiety about future sessions, including level of preparation and education, physical and emotional support, and setting during the session.Conclusion Better preparation beforehand, an optimized treatment setting, and emotional and psychological support during (es)ketamine sessions can help patients to “let go” and may lead to better quality of care and outcomes. Recommendations to improve quality of patient care in (es)ketamine treatment are provided, including suggestions for the training of nurses and other support staff.
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Background: Clinical trials are currently investigating the potential of substance-assisted psychotherapy (SAPT) as treatment for several psychiatric conditions. The potential therapeutic effects of SAPT may be influenced by contextual factors including preparation prior to and integration after the substance-assisted therapy sessions. Aims: This systematized review outlines recommendations for current practice in preparatory sessions in SAPT including safety measures and screening procedures, preparation of set and setting, session contents, methods, and roles, prerequisites, and appropriate conduct of therapists. Methods: A systematized review of the literature was conducted based on PRISMA guidelines. MEDLINE (OVID), PsycINFO (OVID), and Cochrane Library were searched and clinical trials, treatment manuals, study protocols, case studies, qualitative studies, descriptive studies, theoretical papers, reviews, book chapters, and conference proceedings published until February 1, 2022 were retrieved. Results: The final synthesis included k = 83 sources. Information about safety measures including screening of participants, set and setting, contextual-, physiological-, and psychological preparation, roles, competencies, prerequisites, and characteristics of the therapists, and the establishment of a therapeutic relationship were summarized and discussed. Conclusion: It is concluded that there is a consensus in the literature about the importance of adequate preparation before the administration of psychoactive substances in SAPT. However, the extent and approaches for these sessions vary across different models and there is a need for timelier and more rigorous qualitative and quantitative investigations assessing different approaches and techniques for the optimal preparation of clients in SAPT.
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Importance Psilocybin therapy shows antidepressant potential; our data link its antidepressant effects to decreased brain network modularity post-treatment. Objective To assess the sub-acute impact of psilocybin on brain activity in patients with depression. Design Pre vs post-treatment resting-state functional MRI (fMRI) was recorded in two trials: 1) Open-label treatment-resistant depression (TRD) trial with baseline vs 1 day post-treatment fMRI (April-2015 to April-2016); 2) Two-arm double-blind RCT in major depressive disorder (MDD), fMRI baseline vs 3 week after psilocybin-therapy or 6 weeks of daily escitalopram (January-2019 to March-2020). Setting Study visits occurred at the NIHR Imperial Clinical Research Facility. Participants Adult male and female patients with TRD or MDD. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies) Study 1: Two oral doses of psilocybin (10mg and 25mg, fixed order, 7 days apart). fMRI was recorded at baseline and one day after the 25mg dose. Study 2: either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’), or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI was recorded at baseline and 3 weeks after the 2nd psilocybin dose, which was the final day of the 6-week daily capsule ingestion. Main Outcome(s) and Measure(s) Beck Depression Inventory and fMRI network modularity. Results Study 1: In 16 adults (mean age [SD], 42.8 [10.1] years, 4 [25%] female), psilocybin therapy was associated with markedly decreased BDI scores at 1 week (mean difference, -21; 95% CI=[-27.3, -14.7], P<.001) and 6 months (mean difference, -14.19; 95% CI=[-21.3, -7.1], P<.001). Decreased network modularity at one day post-treatment correlated with treatment response at 6 months (Pearson, 0.64; P=.01). Study 2: In 43 adults (42.7 [10.5] years, 14 [33%] female), antidepressant effects favoured the psilocybin-arm at 2 (mean difference, -8.76; 95% CI=[-13.6, -3.9], P=.002) and 6 weeks (mean difference, -8.78; 95% CI=[-15.6, -2.0], P=.01). Specific to the psilocybin-arm, improvements at the 6-week primary endpoint correlated with decreased network modularity (Pearson, -0.42, P=.025). Conclusions and Relevance Consistent efficacy-related functional brain changes correlating with robust and reliable antidepressant effects across two studies suggest a candidate antidepressant mechanism for psilocybin therapy: decreased brain network modularity. Trial registration ClinicalTrials.gov identifier: NCT03429075
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The sense of self has always been a topic of high interest in both psychoanalysis and most recently in neuroscience. Nowadays, there is an agreement in psychoanalysis that the self emerges from the relationship with the other (e.g., the caregiver) in terms of his/her capacity to attune, regulate, and synchronize with the emergent self of the infant. The outcome of this relational/intersubjective synchronization is the development of the sense of self and its regulatory processes both in dynamic psychology and neuroscience. In this work, we propose that synchrony is a fundamental biobehavioral factor in these dialectical processes between self and others which shapes the brain–body–mind system of the individuals, including their sense of self. Recently in neuroscience, it has been proposed by the research group around Northo􀀀 that the self is constituted by a brain-based nested hierarchical three-layer structure, including interoceptive, proprio-exteroceptive, and mental layers of self. This may be disrupted, though, when traumatic experiences occur. Following the three levels of trauma theorized by Mucci, we here suggest how di􀀀erent levels of traumatic experiences might have an enduring e􀀀ect in yielding a trauma-based topographic and dynamic re-organization of the nestedmodel of self featured by dissociation. In conclusion, we propose that di􀀀erent levels and degrees of traumatic experience are related to corresponding disruptions in the topography and dynamic of the brain-based three-layer hierarchical structure of the self.
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Background: Cognition that is not dominated by thinking in terms of opposites (opposite diminishing) or by making judgments (non-judging) can be found both in Buddhist/mindfulness contexts and in mental states that are fostered by dissociative psychedelics ( N -methyl-D-aspartate antagonists) such as ketamine. Especially for the Buddhist/mindfulness case, both opposite diminishing and non-judging have been proposed to relate to mental well-being. Whether ketamine-occasioned opposite diminishing and/or non-judging relate to increased mental well-being in the form of antidepressant response is unknown, and was investigated in the present study. Methods: In this open-label outpatient study, the dose level and frequency for the ketamine infusions were adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits—a novel dose regimen that we term personalized antidepressant dosing . In general, treatment started with an initial series of ketamine infusions with a dosage of 0.5 mg/kg body weight and was then adjusted (usually increased). A possible relationship between ketamine-induced antidepressant benefits and retrospectively reported peri-infusion experiences of opposite diminishing and non-judging was assessed based on a total of 45 ketamine-infusion treatment sessions from 11 different patients suffering from depression. Opposite diminishing and non-judging were measured with the two items from the Altered States of Consciousness Inventory (ASCI) that measure these concepts. Depression was measured with the Beck Depression Inventory (BDI-II). Results: Peri-infusion experiences of both opposite diminishing and non-judging were associated with antidepressant responses confirming our hypothesis. Furthermore, opposite diminishing and non-judging were closely related to one another while relating to antidepressant response in distinguishable ways. Conclusion: Future controlled randomized trials with dissociative and other psychedelics and with a larger number of participants are needed to establish the possible link of psychedelically induced opposite diminishing and non-judging with an antidepressant response more firmly.
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The heralded psychedelic renaissance is currently at a new level where psychedelics are being normalized. Medicalization and the ongoing introduction of market forces are imposing a trend in which psychedelic treatments are reduced to focus into strictly pharmacological and psychological effects on the self, rather than interactions with broader social context. Such narrowing of how psychedelic treatments are being conceived, used, and researched is a source of concern for those who understand that psychedelics’ therapeutic effects as also derived from socially and culturally meaningful elements. Alienation – the sense of isolation from others – and the mental health problems associated with it are on the rise. Consequently, there is not only a need for new therapies but also for a renewed social adhesion and a commitment to a more just and equal society. Psychedelics have a long history of bringing people together, facilitating intense shared experiences, and revitalizing cultures. This social dimension of use of psychedelics—psychedelic sociality—should be considered in the current mainstreaming, as therein lies their potential to support change in individual therapy and beyond. This multidisciplinary research topic of psychedelic sociality invited scholars to discuss these issues through empirical research, reviews, perspectives, and theoretical papers. Overall, 21 papers were accepted to this research topic, covering different sections of Frontiers (Neuropharmacology, Psychopharmacology, Ethnopharmacology, Personality and Social Psychology, and Consciousness Research). We are especially proud of the broad scope of this issue and the diversity of disciplines represented in it. We believe that a beneficial mainstreaming of psychedelics requires going beyond the boundaries of disciplinary orientation. Interdisciplinary integration is necessary for the paradigmatic shift in mental health that many are yearning for: a shift from a narrow biomedical model to an expanded biopsychosocial model that emphasizes the interplay between biological, psychological, sociopolitical and environmental factors in mental health. The centrality of the experience and set & setting in psychedelic research is an invitation to transcend some of the boundaries between the natural sciences and the humanities (see Langlitz et al. (2021). The biopsychosocial model is especially relevant to psychedelic research because to answer questions regarding how psychedelics function, we must incorporate different levels of inquiry – from receptors to persons to culture.
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Expanding on the work of Forstmann and Sagioglou, this study investigated the differences in personality and pro-environmental behavior (PEB) as a function of psychedelic-occasioned mystical experiences. A sample of 240 participants with prior psychedelic experience completed an online survey. Data were collected on participants’ psychedelic-occasioned mystical states, personality, and self-reported PEB. A measure of behavioral PEB was also included (Charity Task). The mean scores on self-reported PEB, openness and agreeableness of participants who met the criteria for a “complete” mystical state, were significantly higher than those who did not. Specifically, those who experienced a mystical state scored higher on the PEB types “eco-shopping and eating” and “one-off domestic conservation actions.” Participants who demonstrated PEB in the Charity Task scored higher on self-reported PEB than those who did not, supporting the task’s validity. Findings suggest that mystical experiences influence PEB. Future research with experimental designs could further illuminate potential causal relationships.
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Modern clinical research on psychedelics is generating interesting outcomes in a wide array of clinical conditions when psychedelic-assisted psychotherapy is delivered to appropriately screened participants and in controlled settings. Still, a number of patients relapse or are less responsive to such treatments. Individual and contextual factors (i.e., set and setting) seem to play a role in shaping the psychedelic experience and in determining clinical outcomes. These findings, coupled with data from literature on the effectiveness of psychotherapy, frame the therapeutic context as a potential moderator of clinical efficacy, highlighting the need to investigate how to functionally employ environmental and relational factors. In this review, we performed a structured search through two databases (i.e., PubMed/Medline and Scopus) to identify records of clinical studies on psychedelics which used and described a structured associated psychotherapeutic intervention. The aim is to construct a picture of what models of psychedelic-assisted psychotherapy are currently adopted in clinical research and to report on their clinical outcomes. Ad-hoc and adapted therapeutic methods were identified. Common principles, points of divergence and future directions are highlighted and discussed with special attention toward therapeutic stance, degree of directiveness and the potential suggestive effects of information provided to patients.
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In this opinion piece we propose the investigation of psychedelic-assisted psychotherapy for the treatment of body dysmorphic disorder (BDD). BDD is a psychiatric disorder characterised by appearance-based preoccupations and accompanying compulsions. While safe and effective treatments for BDD exist, non-response and relapse rates remain high. Therefore, there is a need to investigate promising new treatment options for this highly debilitating condition. Preliminary evidence suggests safety, feasibility, and potential efficacy of psychedelic treatments in disorders that share similar psychopathological mechanisms with BDD. Drawing on this evidence, as well as on relevant qualitative reports and theoretical proposals, we argue that it would be worthwhile to conduct a phase 2a study aimed at assessing the safety and feasibility of psychedelic-assisted psychotherapy in BDD. We also offer some suggestions for how future research ought to proceed.
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Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595
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Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybinassisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network. © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
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Qualitative research, like all scientific research, consists of comparing ideas with observations. In good research, the ideas are thereby changed—strengthened, weakened, qualified, or elaborated. Criteria for evaluating qualitative research focus both on the process and on the product—that is, on the research methods that are used and on the changed ideas themselves (the interpretation). Many qualitative investigators explicitly reject the possibility of absolute objectivity and truth. The concept of objectivity is replaced by the concept of permeability , the capacity of understanding to be changed by encounters with observations. Investigators argue that we cannot view reality from outside of our own frame of reference. Instead, good practice in research seeks to ensure that understanding is permeated by observation. Investigator bias can be reframed as impermeability (interpretations not permeated by empirical observations). Good practice in reporting seeks to show readers how understanding has been changed. The traditional goal of truth of statements is replaced by the goal of understanding by people . Thus, the validity of an interpretation is always in relation to some person, and criteria for assessing validity depend on who that person is (eg, reader, investigator, research participant). Qualitative research differs from traditional quantitative research on human experience in several ways. Results are typically reported in words rather than primarily in numbers. This may take the form of narratives (eg, case studies) and typically includes a rich array of descriptive terms, rather than focusing on a few common dimensions or scales. Investigators use their (imperfect) empathic understanding of participants' inner experiences as data. Events are understood and reported in their unique context. Materials may be chosen for study because they are good examples rather than because they are representative of some larger population. Sample size and composition may be informed by emerging results (eg, cases chosen to fill …
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A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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For many years, there have been heated debates about the best way to evaluate the efficacy and effectiveness of psychological therapies. On the one hand, there are those who argue that the randomized controlled trial (RCT) is the only reliable and scientifically credible way to assess psychological interventions. On the other hand, there are those who have argued that psychological therapies cannot be meaningfully assessed using a methodology developed to evaluate the impact of drug treatments, and that the findings of RCTs lack "external validity" and are difficult to translate into routine clinical practice. In this article, we advocate the use of mixed-method research designs for RCTs, combining the rigor of quantitative data about patterns of change with the phenomenological contextualized insights that can be derived from qualitative data. We argue that such an approach is especially important if we wish to understand more fully the impact of therapeutic interventions within complex clinical settings. To illustrate the value of a mixed-method approach, we describe a study currently underway in the United Kingdom, in which a qualitative study (IMPACT-My Experience [IMPACT-ME]) has been "nested" within an RCT (the Improving Mood With Psychoanalytic and Cognitive Behavioral Therapy [IMPACT] study) designed to evaluate the effectiveness of psychological therapies in the treatment of adolescent depression. We argue that such a mixed-methods approach can help us to evaluate the effectiveness of psychological therapies and support the real-world implementation of our findings within increasingly complex and multidisciplinary clinical contexts. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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We review the historical debate about the assessment of psychotherapy outcome, along with the current status of outcome research. Although strides in statistical techniques have allowed us to conclude that psychotherapy is effective, we argue that typical statistical measurement does not allow researchers to demonstrate the complexity of change for individuals. We thus recommend that researchers include individualized and qualitative approaches in their assessments of psychotherapy outcome. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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Presents an integrative model for a central aspect of change in psychotherapy. According to the assimilation model, clients in successful psychotherapy follow a regular sequence in processing their problematic experiences as these are assimilated into schemata developed in the therapeutic interaction. The model's principal concepts include schema, problematic experience, and assimilation and accommodation. Stages of assimilation are discussed, and case illustrations of a 37-yr-old man and a 37-yr-old woman illustrate this process. Advantages of the assimilation model for research, for clinicians, and for the therapeutic relationship are addressed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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The present study represents one of the first comparisons of the long-term effectiveness of traditional cognitive behavior therapy (i.e., Beckian cognitive therapy; CT) and acceptance and commitment therapy (ACT). One hundred thirty-two anxious or depressed outpatients were randomly assigned to receive either CT or ACT, and were assessed at posttreatment (n=90) and at 1.5-year (n=91) follow-up. As previously reported, the two treatments were equivalently effective at posttreatment according to measures of depression, anxiety, overall (social/occupational/symptom-related) functioning, and quality of life. However, current results suggest that treatment gains were better maintained at follow-up in the CT condition. Clinical significance analyses revealed that, at follow-up, one-third more CT patients were in the clinically normative range in terms of depressive symptoms and more than twice as many CT patients were in the normative range in terms of functioning levels. The possible long-term advantage of CT relative to ACT in this population is discussed.
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Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.
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A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.
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In a matter of hours, mind-altering substances may induce profound psychological realignments that can take decades to achieve on a therapist's couch