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Fully saturated sequential mediation models exploring the relationship between therapeutic alliance during the second psilocybin session and depression scores 6 weeks following a two-dose course of psychedelic-assisted psychotherapy. Sequential mediation of therapeutic alliance via pre-session rapport and B) Mystical-type Experiences, but not A) Emotional Breakthrough was supported by the models for this second session. Importantly, depression severity at 6 weeks was controlled for midline (3 weeks post-first dose) depression scores, which by itself accounted for R ² = 0.55, i.e., 55% of variance in the final outcome. Greater midline depression severity significantly predicted worse therapeutic alliance and pre-session rapport scores. Decimal values represent standardised regression coefficients (β values) for significant (solid, p > 0.1) but not non-significant (dashed) paths. The subscript number two refers to the second psilocybin session. ☨ indicates p < 0.1, *p < 0.05, **p < 0.01, ***p < 0.001
Source publication
Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psy...
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Citations
... Importantly, the adoption of acceptance and "surrender", rather than avoidant responses, during psychedelic experiences is thought to facilitate so-called "emotional breakthroughs" 37 . Alongside preparation 30 , "set and setting" variables 47 , and a strong therapeutic alliance 48 , effective responses and skilful navigation of challenging psychological states may therefore be particularly crucial predictors of therapeutic success. ...
... Lastly, the Facilitator Responses theme underscored the critical role of guides or therapists in providing physical and emotional support and introducing new elements to assist participants during challenging moments. This aligns with existing evidence that the quality of this relationship predicts emotional breakthrough and improvements in mental health 48 . Examination of responses and thematic analysis led to the development of the 26-item ReCiPE scale ( Table 2, Fig. 1). ...
... Acceptance and Reappraisal strategies, aligning with approaches like ACT and Mindfulness Based Stress Reduction (MBSR) 87,88 , showed a positive association with emotional breakthroughs, suggesting the value of incorporating mindfulness and acceptance-based practices into psychedelic interventions 50,80,83,[89][90][91] . Social Support and Disclosure strategies also showed positive associations with emotional breakthroughs, aligning with recent research on interpersonal support in psychedelic contexts 48,92,93 . These patterns emphasise the complex interplay between emotional experiences and coping mechanisms, highlighting the need for flexible, tailored therapeutic approaches. ...
Psychedelic substances are garnering renewed interest for their potential therapeutic applications, yet the mechanisms by which challenging experiences during psychedelic use contribute to positive outcomes remains poorly understood. Here we present a mixed-methods investigation into the strategies individuals employ to navigate difficult psychedelic experiences and their relationship to emotional breakthrough. Qualitative analysis of accounts from psilocybin retreat participants (n = 16) informed the development of the Responses to Challenging Psychedelic Experiences Inventory (ReCiPE). In a subsequent online survey (n = 529), exploratory factor analysis of the ReCiPE revealed three primary response strategies: Acceptance and Reappraisal, Sensory Regulation and Physical Interaction, and Social Support and Disclosure. Exploratory correlation and multiple regression analyses demonstrated significant relationships between different types of challenges, response strategies and emotional breakthrough. Notably, Acceptance and Reappraisal, and Social Support and Disclosure strategies were positively associated with greater emotional breakthrough. Fear-related challenges were negatively associated with emotional breakthrough and involved fewer adaptive coping strategies. These findings elucidate the complex interplay between challenging experiences and adaptive responses in psychedelic contexts, offering insights for optimising therapeutic protocols and enhancing safety in both clinical and non-clinical settings.
... To promote a healthy 'set, ' it is standard practice to include extensive psychological preparation in the form of multiple pre-dosing sessions in a calming therapeutic environment. Although head-to-head trials are lacking comparing outcomes with therapeutic support versus without, it is thought that at least a portion of the outcomes seen in psychedelic research are attributed to the psychotherapeutic support and therapeutic alliance formed during the trial (Zeifman et al., 2024;Murphy et al., 2021). Indeed, when LSD was made available by Sandoz, the package insert mentioned the drug was to be used in conjunction with psychotherapy (Goodwin et al., 2024). ...
Psychedelic compounds continue gaining scientific and regulatory traction as potential new treatments for psychiatric disorders. While most psychiatrists will likely not work directly with these compounds, psychedelic research practices provide insights that may improve conventional psychiatric care. Through its emphasis on ‘set and setting’ (mindset and environment, respectively), psychedelic research highlights the importance of non-pharmacologic factors maximizing therapeutic outcomes. While psychedelics and serotonergic antidepressants are distinctly different in their subjective experience, new findings suggest mechanistic overlap between them. Both have been found to modulate neurotrophins, enhance neuroplasticity, and reopen critical periods of learning, molded by the environmental context in which they are administered.
This paper will argue that by integrating insights from psychedelic research (particularly set and setting), depression treatment outcomes in traditional psychiatric settings can improve by optimizing non-pharmacological factors in treatment, including the provision of high-quality psychotherapy.
... Attempts to locate the risk factors in the phenomenology of the acute drug or meditation experience (e.g., difficulty, mystical experience) itself have been mixed Haijen et al., 2018). Recommendations include more attention to "set and setting, " which includes both usercentered and contextual factors (Bremler et al., 2023;CarhartHarris et al., 2018;Haijen et al., 2018), and the overall "psychosocial matrix, " particularly interactions and power dynamics between participant and guide, teacher, or other par ticipants; implicit ideology; and assumptions of the therapeutic model (Canby et al., 2020;Devenot et al., 2022;McNamee et al., 2023;Meikle et al., 2024;Murphy et al., 2021). These contextual factors warrant closer examination through an assessment of the con texts of psychedelics use. ...
... Nine out of ten clinics included in our study offered concurrent psychotherapy, though it remains unclear whether these psychotherapeutic offerings are consistent with the standard therapeutic model published in literature. Standard model generally includes two clinicians per patients, where clinicians have extensive professional experience and training with the effects of psychedelic compound [36]. The clinical team spends a considerable amount of time with patients, approximately 35-40 hours [36]. ...
... Standard model generally includes two clinicians per patients, where clinicians have extensive professional experience and training with the effects of psychedelic compound [36]. The clinical team spends a considerable amount of time with patients, approximately 35-40 hours [36]. The "set and setting" play a significant role in shaping the process and outcomes of psychedelic experience. ...
... The term "set" encompasses psychological factors such as mood and intentions, while "setting" involves environmental factors such as social and cultural space [35]. Recognizing the importance of these influences, therapeutic alliance and rapport have been described as determinants of efficacy and safety of mental health treatment with psychedelic medicines [36]. A literature review of trials found that adverse events such as mania can be precipitated in patients with bipolar disorder when using psychedelics [37], emphasizing the necessity of well-trained practitioners, and appropriate "set" and "setting" to address these potential adverse effects if they arise. ...
Psychedelics, including ketamine, 3,4-Methyl enedioxy methamphetamine (MDMA), and psilocybin, have gained attention for their potential therapeutic role in mental health treatment. While recreational use is prohibited in Canada, medicinal exemptions can be granted. There are several psychedelic clinics in Ontario, Canada, promoting the use of psychedelics for a variety of medical indications. Our objective was to identify the indications for which psychedelics are being prescribed in Ontario clinics and assess the quality of evidence used to support these claims. Internet searches were conducted using Google and Bing to identify psychedelic clinics in Ontario. Inclusion criteria was as follow: clinics were physically located in Ontario, had a functioning website link, and demonstrated involvement of a licensed physician or nurse practitioner. Identified clinics were evaluated for their claims of effectiveness, the quality of evidence used to support these claims, and statements on psychedelic-related harms. The cited studies were appraised for quality using Oxford Centre for Evidence-Based Medicine Levels of Evidence, “level 5” being the lowest quality and “level 1” being the highest quality. Out of 200 search results, 10 psychedelic clinic websites met our inclusion criteria. These clinics advertised psychedelics for 47 medical conditions, most commonly for depression. Only 2 out of 10 clinics described potential risks associated with psychedelic use. There were 29 studies cited by these websites, majority coming from “level 4” evidence consisting of case-series and case-control studies. Overall, the cited evidence quality was low to moderate. Psychedelic clinics in Ontario promote a wide range of medical indications for psychedelics using primarily low to moderate “level 4” evidence. There is limited information shared on the potential adverse effects of psychedelics. Our study emphasizes the importance of using transparent and high-quality evidence by clinics and clinicians to ensure safe and effective use of psychedelics in mental health treatments.
... A recent qualitative study explored patient experiences with psychedelic treatments and created a list of recommendations to optimize treatment approaches (Breeksema et al. 2024). During the preparatory phase, establishing a strong rapport between the patient and therapist is crucial as a robust therapeutic alliance has been associated with improved therapeutic response in multiple studies (Murphy et al. 2022;Levin et al. 2024). Allocating sufficient time for preparation sessions allows trust to develop, which is especially important as some patients may require more time than others to feel comfortable. ...
There is a large and rapidly growing body of literature investigating the therapeutic effects of classic psychedelics in affective and anxiety disorders, but very few studies have examined the inverse of this, that is, the potential for psychedelics to inflict anxiety and affective symptoms. A systematic literature search was performed and 39 papers were included in the final review to qualitatively synthesize the current literature on anxiety and affective disorders related to the use of classic psychedelics. Persisting disorders were less frequent but generally occurred in individuals who presented with several risk factors (overdose, polydrug use, unstructured recreational setting, psychosocial stress, personal/familial psychiatric histories). When psychedelics were administered in clinical studies under the framework of psychedelic-assisted therapy, the incidence of enduring anxiety and affective symptoms was low. In most cases, acute transient anxiety emerged and resolved during the dosing session without the need for additional treatment interventions. The nuance of such cases is discussed, shedding light on the role of emotional catharsis in the therapeutic process. Several suggestions are proposed to enhance patient safety including strengthening the therapeutic alliance, ensuring adequate mental preparation, acclimating to high doses and providing on-going therapeutic support.
... These variables can be assessed with various measures with established validity and reliability. 89,90,[93][94][95] Attitude toward hypnosis is a construct that is related to several of the recommendations mentioned above. Due to popular media, many people have misconceptions about hypnosis and hypnotherapy that affect willingness to use these interventions as well as outcome expectancy. ...
There is an abundance of outcomes research for clinical hypnosis showing promising results. Nonetheless, hypnosis is still underutilized in clinical care. For a behavioral intervention to enter mainstream clinical care, efficacy needs to be demonstrated with exceptionally high quality of evidence, and its reporting needs to be complete and sufficiently clear to enable replication and clinical use. The present article provides best practice guidelines formulated by the Task Force for Establishing Efficacy Standards for Clinical Hypnosis for conducting and reporting clinical hypnosis research.The recommendations are presented in two tiers. Tier I recommendations include essential best practices, such as a call for the use of detailed research and intervention manuals, plans for and reporting of participant-education about hypnosis, the use of hypnotizability scales with good psychometric properties, and clear reporting of the hypnotizability measurement. Tier I also includes the sharing of intervention manuals, the reporting of the induction procedure, the labeling of the intervention for participants, and the definition of hypnosis used. Tier II includes preferred recommendations, calling for measurement of adherence to home practice, measurement of hypnotizability using scales with both subjective and behavioral measures of responsiveness, and the involvement of participants from the full hypnotizability spectrum. Tier II also includes the assessment of variables related to proposed mechanisms of action, the reporting of participants prior hypnosis experiences, and the relationship of expectancies and treatment outcomes.This list of recommendations will be useful for researchers, reviewers, and journal editors alike when conducting, reporting, or evaluating studies involving clinical hypnosis.
... Qualities of the subjective experience have been found to be predictive of subsequent positive and negative therapeutic outcomes (Herrmann et al., 2022;Roseman, Nutt, & Carhart-Harris, 2018), indicating the nature of experience may be an important determinant of subsequent therapeutic trajectories (Yaden & Griffiths, 2020). Specifically, so-called 'peak' or 'mystical-type experiences' (Barrett, Johnson, & Griffiths, 2015;Bogenschutz et al., 2015;Garcia-Romeu, Griffiths, & Johnson, 2015;Johnson, Garcia-Romeu, Cosimano, & Griffiths, 2014;Roseman et al., 2018;Studerus, Gamma, & Vollenweider, 2010), 'challenging experiences' (Barrett, Bradstreet, Leoutsakos, Johnson, & Griffiths, 2016;Gashi, Sandberg, & Pedersen, 2021;Roseman et al., 2018), and 'emotional breakthrough' (Dougherty et al., 2023;Haijen et al., 2018;Kettner et al., 2021;Lyons et al., in prep;Murphy et al., 2021;Peill et al., 2022;Roseman et al., 2019) have been related to therapeutic outcomes (Peill et al., 2022). ...
... Internal consistency of EBI is excellent (Cronbach's α = 0.932). Predictive validity of EBI was first demonstrated through correlation with well-being 2-weeks post psychedelic experience (r = 0.294, p = 0.005; Roseman et al., 2019) and has since been further supported Murphy et al., 2021;Peill et al., 2022). ...
Background
Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the ‘Imperial Psychedelic Predictor Scale’ (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience.
Methods
Using four independent datasets in which the IPPS was completed prospectively – two online surveys of ‘naturalistic’ use ( N = 741, N = 836) and two controlled administration datasets ( N = 30, N = 28) – we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS.
Results
Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of ‘mystical’, ‘challenging’, and ‘emotional breakthrough’ experiences. In a controlled administration dataset ( N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another ( N = 30), rapport was related to emotional breakthrough explaining 9% of variance.
Conclusions
Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.
... Although sexual abuse is an issue shared with traditional psychotherapy, it is particularly concerning with psychedelics, given the acute vulnerability and increased suggestibility that accompany the subjective effects induced by these drugs. 26 Psychedelics may also affect therapeutic alliance between client and provider, 33 arguably to a fault in some cases, putting the patients at even greater risk of suggestion. Indeed, McNamee et al. 5 describe the case of an MDMA-assisted psychotherapy study participant who was inappropriately touched during an MDMA dosing session, developed an extreme bond and dependency with the (married) therapist dyad, and subsequently moved in with them after the study ended, while the sexual misconduct continued. ...
Introduction: Psychedelic substances have been used for centuries in various cultural and religious contexts, and more recently, in clinical research and therapy. There is a surge of interest in psychedelics, and psychedelic-assisted psychotherapy is becoming increasingly accessible. However, most individuals using psychedelics do so outside of therapeutic contexts. It is important to understand the adverse experiences that may occur with psychedelic use, as well as adverse events that may happen even in therapeutic contexts.
Materials and Methods: We conducted an anonymous online survey of individuals who self-reported past psychedelic use. We asked about the frequency of experiencing 12 different adverse experiences when using psychedelics, and if they or someone they know was the victim of inappropriate sexual contact by a psychedelic sitter, guide, or practitioner. Participants could also describe other adverse experiences.
Results: Among 1,221 participants, most reported having adverse experiences such as being frightened (74.3%), sadness (58.6%), feeling their body shake or tremble (54.3%), and loneliness (51.6%) during their psychedelic experiences. About half of participants reported having some other adverse experience, and one in ten participants had adverse physical reactions. About one-third of participants knew someone who was arrested for possession or use of psychedelics; 8% reported that they or someone they know was the victim of inappropriate sexual contact by a psychedelic sitter, guide, or practitioner; and one-quarter of participants knew someone who experienced a severe adverse event other than inappropriate sexual contact or arrest.
Conclusion: Despite beneficial effects, psychedelic experiences can also be challenging, distressing, or even harmful. Adverse events can increase the risks of psychological harm, legal problems, stigma, and public health issues. Therefore, it is essential to prevent, identify, manage, and treat adverse events during psychedelic experiences to ensure the safety and well-being of the participants and the facilitators, and create opportunities for “integration” even with unguided sessions.
... An aversion to carers amongst people who use psychedelics provokes consideration of how education could support consumers to care for themselves under the influence of psychedelics, improving their understanding of subjective effects and the relationship of these effects with dosage and other biological factors, such as staying hydrated when drinking alcohol. In contrast to clinical settings where preliminary evidence suggests that therapeutic care is highly appreciated and may be important for therapeutic effects (Murphy, et al., 2022;Thal, et al., 2022), people who use psychedelics in other settings/recreationally seem to appreciate psychedelic independence. This preference may be because this population does not necessarily take psychedelics to treat psychiatric disorders but, for instance, to engage in self-exploration, increase creativity, or to increase existential awareness (Pestana, Beccaria, & Petrilli, 2021). ...
... The small number of participants limits formal significance testing of the relationships between memory, EEG, and behavioral assays and midazolam dose. Because it was a dose-finding study, there was also no placebo control or assessment of variables such as expectation [103], suggestibility [104], therapeutic alliance [51], and blinding effectiveness [105]. The normative ASC data used for comparison were obtained from a patient population 24 h after psilocybin administration, rather than from healthy volunteers during the dosing session. ...
Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.
