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New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy

New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy OPINION published: 10 September 2021 doi: 10.3389/fpsyt.2021.727050 New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy 1 2 Tehseen Noorani * and Jonny Martell 1 2 Department of Anthropology, Durham University, Durham, United Kingdom, Centre for Psychedelic Research, Imperial College London, London, United Kingdom Keywords: psychedelic therapy, bubble, opportunity, psychedelics, hallucinogens, regulation INTRODUCTION The publication in April 2021 of the Imperial College London Phase II study investigating the efficacy of psilocybin-assisted therapy vs. escitalopram for depression reported differences in the primary outcome measure (the QIDS-SR16) between experimental and control arms as statistically insignificant (1). However, secondary measures of depression, and other relevant measures (see Appendix), favored psilocybin to escitalopram. Soon thereafter, a range of expert commentaries offered interpretations, including that the researchers were unfortunate in their choice of pre-registered primary outcome, the trial was underpowered perhaps revealing an overconfidence in designing the study, and the limitations of depression rating measures to capture the return of positive mood and well-being. Partially in response to these publications, discussions in research and online communities Edited by: have grown around the over-hyping of psychedelic treatments, bringing into focus concerns over Graham Campbell, Hammersmith Medicines Research, psychedelic therapy trial methodology [for a peer-reviewed critique, see (2)]. This opinion piece United Kingdom explores these concerns to propose a response to this special issue’s question, “Can Psychedelic Therapies Open a New Frontier in Mental Healthcare (Or Will the Bubble Burst)?” Drawing on Reviewed by: James Rucker, our experiences of working within psychedelic clinical trials and NHS psychiatry, we offer here a King’s College London, deflationary answer to this question, suggesting both will occur and outlining some of the facets, United Kingdom stakes and opportunities entailed. *Correspondence: Tehseen Noorani PART I: THE BURSTING BUBBLE tehseen.n.noorani@durham.ac.uk The enthusiastic reception and excitement over the potential of psychedelics in academic, medical, Specialty section: public, and even political arenas is buttressed by the growing call for new psychiatric treatments, This article was submitted to concerns over the long-term prescription of antidepressants to growing patient numbers without Psychopathology, a concomitant reduction in psychiatric morbidity, and increasing evidence of withdrawal effects a section of the journal (3, 4). We define the “psychedelic therapy bubble” as an overestimation of its promise that is not Frontiers in Psychiatry justified by what is and can be known about its therapeutic potential. Coining the term promissory Received: 17 June 2021 science, Davis and Abraham describe how, Accepted: 17 August 2021 Published: 10 September 2021 “in connection with the manufacturer’s promotion of apparently hopeful clinical trial results in the lead Citation: up to a new drug application for marketing approval...both the hopeful results and the novelty of the Noorani T and Martell J (2021) New new drug’s hypothesized mechanism of therapeutic efficacy may be elevated to great clinical significance Frontiers or a Bursting Bubble? to an expectant medical profession, patient population and stock market” [(5), p.268] [see also (6, 7)]. Psychedelic Therapy Beyond the Dichotomy. Front. Psychiatry 12:727050. Understanding the psychedelic therapy bubble in terms of promissory science highlights the doi: 10.3389/fpsyt.2021.727050 feedback loops whereby inflated expectations are themselves shaping psychedelic therapy’s Frontiers in Psychiatry | www.frontiersin.org 1 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy potential (8). Economically, the bubble sustains sufficient And fourthly, we are yet to understand the nature and extent of initial investments to offset the direct and infrastructural costs ethical dilemmas that will emerge. For example, with regards to of bringing psychedelic therapies to market. Consequently, “false memory syndrome,” the complexity of working with the commercial imperatives of efficiency, standardization, and veracity of unmediated knowledge has recently been explored scalability are steering ongoing research. Advocates of (17), posing a challenge for manualized and protocolized therapy these processes argue that this is either appropriate or at training programs. least necessary, in order to re-invigorate psychiatry’s tired pharmacopeia (9). Culturally, the success of psychedelic therapy PART II: NEW FRONTIERS has been steered by actors seeking redemption for psychedelic- assisted and related healing practices in the wake of psychedelic Recognizing that psychedelic therapy is a bubble that will burst prohibition at the end of the 1960s, and the researchers among should not be taken to mean that psychedelics do not offer them have brought particular interpretive frameworks for “new frontiers.” On the contrary, we outline four areas below in understanding the nature and value of psychedelic experiences. which psychedelic therapy has the potential to transform mental This includes the foregrounding of the therapeutic value of the healthcare, even if it is not approved and mainstreamed to the mystical-type experience, which has begun to be problematized extent currently anticipated. from various quarters as overly simplistic [e.g., (10)]. Novel Compounds The concern with psychedelic therapy being a bubble that may burst is sometimes reduced to a warning against a repeat of drug Psychedelic research has stimulated interest in a trove of new psychedelic-inspired compounds (for example, see MagicMed prohibitionist laws and policies [e.g., (11)]. Yet the more colorful TM narrative of psychedelic research as a casualty in Nixon’s fight Industries Inc’s Psybrary ), with differing pharmacological and risk profiles. We can expect the effects they produce to range against the counterculture has in recent years been tempered by historical investigation into the effects of an impasse between from therapeutic to toxic and psychoactive to non-psychoactive. With the proliferation of these compounds, we anticipate a paradigms for conducting psychedelic therapy research and the growing imperatives of standardized randomized controlled trial growing discussion about the necessity of the psychedelic experience for therapeutic gain [e.g., (18, 19)]. Additionally, the (RCT) designs (12, 13). Moreover, today’s situation is different development of “neutralization technologies” for terminating the in key ways: firstly, scholars have documented how medical psychedelic experience and drug administration through novel professionals, regulators, and patient groups have pushed for target-controlled intravenous infusion techniques (20) suggest “pragmatic” and “adaptive” trial designs in the intervening to us that therapeutic practices will be developed that combine decades (14). Secondly, today’s psychedelic clinical researchers both “shutting down” and “opening up” to offer new options are self-consciously aware of, and keen to prevent, a return to psychedelic prohibition, carefully proffering a “sober objectivity,” for experiential manipulation, in line with the growing call for personalized medicine. and emphasizing psychedelics as therapeutic agents as opposed to subversive agents of social and political change (15). Thirdly, Psychedelic Therapy as Driving Interest in we suggest psychedelic therapy is well-suited to the growing calls for psychiatry to be more oriented to the relational (16). Suggestion Nevertheless, bubbles burst, and we offer four axes along Psychedelic therapy trials are generating data we suggest which to consider this in relation to psychedelic therapies. Firstly, could fruitfully be conceptualized through the framework critiques of psychedelic therapy trial publications have warned of of the sensitivity of therapeutic altered states to suggestion. common features of the RCTs that are likely to be inflating effect This connects several literatures: a tradition of psychedelic sizes: participant self-selection, stringent screening procedures, research that proposes the drugs produce states of heightened small sample sizes, and difficulty in maintaining blinding in suggestibility against a longer historical interest in hypnosis research trials (2). Secondly, as the therapies gain legitimacy, (21–24); psychedelics as psychoplastogens, increasing cognitive the psychedelic research community is itself changing. Until and emotional flexibility (25–27)); the field of placebo studies recently, this community has comprised researchers who were (28–30); ritual theory (31, 32) and the study of “common factors” willing to accept the professional ramifications of working across psychotherapies (33) alongside other process-oriented in a stigmatized area. While the early advocates of any new research into psychological change. By bringing these literatures treatment can be expected to be enthusiastic, the interaction into a fuller encounter, we imagine a range of conceptual effects of any researcher bias with psychedelics’ sensitivity to the distinctions, methodological considerations, and theories, context of their use would contribute especially large outcome animating new directions for psychedelic therapy research. confounders, leading to limited replication of the early findings. Considering the above literatures, it would be timely to bring Thirdly, we should anticipate a growth in adverse outcomes as together psychedelic researchers and experts in these related the hype grows, the participant/patient pool is widened, and areas, to identify trial designs and interpretive frameworks psychedelic therapies are provided in more streamlined ways. that support mutually fruitful lines of inquiry. Interdisciplinary Increasingly diverse patient populations hopeful of being cured research could reveal the processes by which the psychedelic will experience rocky “landings” post-treatment, the cost of experience may be “baking in” a particular message or self- which will be borne downstream of trial analysis end points, reorientation that has been primed or reinforced by the other thereby falsely inflating favorable health economic calculations. study components. Without wanting to foreclose what such Frontiers in Psychiatry | www.frontiersin.org 2 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy conversations will open up, we are particularly interested in two broadly, owing to how sensitive psychedelic experiences are to avenues of inquiry: firstly, more fully measuring the expectations the context of their use. Some researchers have called for more held by participants at different stages of the intervention would detailed measurement of the context of psychedelic therapy in reveal more than potential confounds within trials—it could order to better grasp its therapeutic mechanisms [cf. (38, 41, 42)], teach us about the looping effects of the bubble itself, by something the growth in survey approaches is endeavoring to indexing how trials are themselves differentially emplaced within do [e.g., (43)]. We wonder what it might mean to circumscribe a timeline of the evolving hype around psychedelic therapies. the generalizability of research findings much more narrowly, Secondly, a fuller engagement with placebo studies suggests the acknowledging not simply that there are additional contextual need to consider more fully the role of uncertainty, hesitation, parameters that need taking into account but that it may not be and doubt in healing through psychedelic therapy (31, 34), and possible to determine intervention effects in any general sense, how these are cultivated through drug-set-setting configurations given the plethora of “experimental contingencies” (2:8) in any that offer the opportunity to “[traffic] in human possibilities given context. rather than in settled certainties” (35). Reflections on the history The need for a more context-sensitive and systematic coupling of placebo studies may also caution against reprising politically of research pre- and post-approval is important. Psychedelic and ethically fraught attempts to identify the suggestible “type” therapies seek approval based upon safety and efficacy data, of person (Phoebe Friesen, personal communication). We worry, and yet their very approval may affect their efficacy and however, that such interdisciplinary enquiry is being sidelined in safety profiles, as mediated by expectations and understandings the rush to approve particular psychedelic therapy packages for of the substances borne of the evolving bubble that their the treatment of particular indications. hype is generating. Psychedelic therapies also challenge any easy separation of safety and efficacy, as when, for example, The Role of Care powerful new meanings and senses of purpose are generated A broad intersecting of psychedelic research and related research that are therapeutic, but only with appropriate structures of literatures also suggests a deeper valuing of the role of care support and care. Existing post-approval regulatory landscapes structures in psychiatric care writ-large. While the imperative are poorly equipped to meet the needs of patients for up- in placebo-controlled antidepressant trials has been to minimize to-date (re-)evaluations of safety and efficacy. Regulators lack the placebo response by limiting patient expectancy and comprehensive and timely data for determining post-approval therapeutic contact (36, 37), this is inverted in the enriched safety issues, much less changes in efficacy, and have failed to spaces and care protocols developed for psychedelic therapies enforce the surveillance measures they currently demand of the (38). These spaces and protocols challenge the reductionism of pharmaceutical industry (44). The shift in onus of responsibility psychopharmacological interventions by drawing attention to to patients and providers to deliver on what is called “post- the relational aspects of care, moving from a compartmentalized marketing surveillance” via reporting systems has largely failed focus on symptoms in need of treatment to a more holistic view to deliver, due to under-use and the constraints posed by of human suffering and the value of meaning-making in health imperatives for data anonymization (45). and wellness. More broadly, the rise of the psychedelic therapy One logical endpoint of the calls for greater context sensitivity bubble has contributed to the growing awareness of a wider and the ongoing monitoring of changing safety and efficacy ecology of healing practices that center the body, space-making, profiles is in the technically-mediated surveillance of psychedelic and spirituality. therapy through adjunctive devices and apps, as seen in calls However, the significant opportunities for psychedelic for the use of ever-more-granular monitoring technologies researchers to refocus psychiatric treatments on enriching in order to adequately power research (46). It remains to and optimizing relations of care is compromised by industry be seen whether such “field approaches” can provide useful pressures, including commercial incentives to foreground findings. Meanwhile, the normalization of such technologies the “drug treatment” model over the crucial (39) but costly raises substantial legal and political concerns, in particular psychotherapeutic work, and a regulatory system designed to around the case for reconsidering proprietary rights in relation evaluate the administration of drugs as stand-alone treatment to data capture. modalities. Emphasizing the relations of care that appear to us to be key to safe and effective psychedelic therapy will also require coordination across scales and disciplines. For example, DISCUSSION some psychedelic advocates are beginning to make the economic case for psychedelic therapies by appealing to the long-term In this opinion piece we have sought to foster greater critical cost-savings achieved if psychedelic therapies are considered a discourse around the broader regulatory, cultural and economic curative rather than a palliative care treatment [in relation to forces shaping psychedelic research. While we have argued for MDMA-assisted psychotherapy, see (40)]. It remains unclear the need to be attentive to how the psychedelic therapy bubble whether this strategy will persuade healthcare payers. is shaping its potential, we end on a note of optimism. In considering the “bubble” as a public health measure in the Regulatory Dynamism wake of the Covid-19 pandemic, Appleton (47) invites us to Finally, we suggest that psychedelic therapy research heralds an imagine bubbles as affording a protected space in the knowledge opportunity to rethink the regulation of drug research more that such a space is temporary. We might then consider Frontiers in Psychiatry | www.frontiersin.org 3 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy this moment an opportunity to develop robust methodologies therapy’s potential to re-invigorate Western psychiatry might be and alliances across research disciplines and with stakeholder better realized. groups, and to inquire into the most pressing research questions of psychedelic therapy, before the bubble bursts. For us, AUTHOR CONTRIBUTIONS these questions include greater consideration of the role of community support structures, psychedelic therapy’s long-term This manuscript emerged out of a series of conversations between effects, what “safety” and “efficacy” mean amongst different TN and JM, followed by the joint writing of the abstract. TN stakeholder groups, and how best to set up harm reduction led the writing of a first draft of the full manuscript. All authors services and infrastructures, all before driving forward the then redrafted the manuscript, together and independently, and mass scaling of pre-maturely-rigid formulations of psychedelic approved the submitted version. therapy. We recognize that this lies in tension with the imperative to scale, itself drawing on the language of a growing ACKNOWLEDGMENTS “mental health epidemic” and exacerbated by the Covid-19 pandemic. We maintain that by integrating the bubble’s shadow The authors would like to thank Albert Garcia-Romeu and before it bursts—or at least deflates [cf. (48)]—psychedelic Roberta Murphy for comments on an earlier draft. REFERENCES 17. Timmerman C, Watts R, Dupuis D. Towards psychedelic apprenticeship: developing a gentle touch for the mediation and validation of 1. Carhart-Harris RL, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, psychedelic-induced insights and revelations. Transcult Psychiatry. (2020) Murphy R, et al. 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Front Pharmacol. (2018) 9:897. doi: 10.3389/fphar.2018. in this journal is cited, in accordance with accepted academic practice. No use, 00897 distribution or reproduction is permitted which does not comply with these terms. Frontiers in Psychiatry | www.frontiersin.org 5 September 2021 | Volume 12 | Article 727050 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Frontiers in Psychiatry Unpaywall

New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy

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OPINION published: 10 September 2021 doi: 10.3389/fpsyt.2021.727050 New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy 1 2 Tehseen Noorani * and Jonny Martell 1 2 Department of Anthropology, Durham University, Durham, United Kingdom, Centre for Psychedelic Research, Imperial College London, London, United Kingdom Keywords: psychedelic therapy, bubble, opportunity, psychedelics, hallucinogens, regulation INTRODUCTION The publication in April 2021 of the Imperial College London Phase II study investigating the efficacy of psilocybin-assisted therapy vs. escitalopram for depression reported differences in the primary outcome measure (the QIDS-SR16) between experimental and control arms as statistically insignificant (1). However, secondary measures of depression, and other relevant measures (see Appendix), favored psilocybin to escitalopram. Soon thereafter, a range of expert commentaries offered interpretations, including that the researchers were unfortunate in their choice of pre-registered primary outcome, the trial was underpowered perhaps revealing an overconfidence in designing the study, and the limitations of depression rating measures to capture the return of positive mood and well-being. Partially in response to these publications, discussions in research and online communities Edited by: have grown around the over-hyping of psychedelic treatments, bringing into focus concerns over Graham Campbell, Hammersmith Medicines Research, psychedelic therapy trial methodology [for a peer-reviewed critique, see (2)]. This opinion piece United Kingdom explores these concerns to propose a response to this special issue’s question, “Can Psychedelic Therapies Open a New Frontier in Mental Healthcare (Or Will the Bubble Burst)?” Drawing on Reviewed by: James Rucker, our experiences of working within psychedelic clinical trials and NHS psychiatry, we offer here a King’s College London, deflationary answer to this question, suggesting both will occur and outlining some of the facets, United Kingdom stakes and opportunities entailed. *Correspondence: Tehseen Noorani PART I: THE BURSTING BUBBLE tehseen.n.noorani@durham.ac.uk The enthusiastic reception and excitement over the potential of psychedelics in academic, medical, Specialty section: public, and even political arenas is buttressed by the growing call for new psychiatric treatments, This article was submitted to concerns over the long-term prescription of antidepressants to growing patient numbers without Psychopathology, a concomitant reduction in psychiatric morbidity, and increasing evidence of withdrawal effects a section of the journal (3, 4). We define the “psychedelic therapy bubble” as an overestimation of its promise that is not Frontiers in Psychiatry justified by what is and can be known about its therapeutic potential. Coining the term promissory Received: 17 June 2021 science, Davis and Abraham describe how, Accepted: 17 August 2021 Published: 10 September 2021 “in connection with the manufacturer’s promotion of apparently hopeful clinical trial results in the lead Citation: up to a new drug application for marketing approval...both the hopeful results and the novelty of the Noorani T and Martell J (2021) New new drug’s hypothesized mechanism of therapeutic efficacy may be elevated to great clinical significance Frontiers or a Bursting Bubble? to an expectant medical profession, patient population and stock market” [(5), p.268] [see also (6, 7)]. Psychedelic Therapy Beyond the Dichotomy. Front. Psychiatry 12:727050. Understanding the psychedelic therapy bubble in terms of promissory science highlights the doi: 10.3389/fpsyt.2021.727050 feedback loops whereby inflated expectations are themselves shaping psychedelic therapy’s Frontiers in Psychiatry | www.frontiersin.org 1 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy potential (8). Economically, the bubble sustains sufficient And fourthly, we are yet to understand the nature and extent of initial investments to offset the direct and infrastructural costs ethical dilemmas that will emerge. For example, with regards to of bringing psychedelic therapies to market. Consequently, “false memory syndrome,” the complexity of working with the commercial imperatives of efficiency, standardization, and veracity of unmediated knowledge has recently been explored scalability are steering ongoing research. Advocates of (17), posing a challenge for manualized and protocolized therapy these processes argue that this is either appropriate or at training programs. least necessary, in order to re-invigorate psychiatry’s tired pharmacopeia (9). Culturally, the success of psychedelic therapy PART II: NEW FRONTIERS has been steered by actors seeking redemption for psychedelic- assisted and related healing practices in the wake of psychedelic Recognizing that psychedelic therapy is a bubble that will burst prohibition at the end of the 1960s, and the researchers among should not be taken to mean that psychedelics do not offer them have brought particular interpretive frameworks for “new frontiers.” On the contrary, we outline four areas below in understanding the nature and value of psychedelic experiences. which psychedelic therapy has the potential to transform mental This includes the foregrounding of the therapeutic value of the healthcare, even if it is not approved and mainstreamed to the mystical-type experience, which has begun to be problematized extent currently anticipated. from various quarters as overly simplistic [e.g., (10)]. Novel Compounds The concern with psychedelic therapy being a bubble that may burst is sometimes reduced to a warning against a repeat of drug Psychedelic research has stimulated interest in a trove of new psychedelic-inspired compounds (for example, see MagicMed prohibitionist laws and policies [e.g., (11)]. Yet the more colorful TM narrative of psychedelic research as a casualty in Nixon’s fight Industries Inc’s Psybrary ), with differing pharmacological and risk profiles. We can expect the effects they produce to range against the counterculture has in recent years been tempered by historical investigation into the effects of an impasse between from therapeutic to toxic and psychoactive to non-psychoactive. With the proliferation of these compounds, we anticipate a paradigms for conducting psychedelic therapy research and the growing imperatives of standardized randomized controlled trial growing discussion about the necessity of the psychedelic experience for therapeutic gain [e.g., (18, 19)]. Additionally, the (RCT) designs (12, 13). Moreover, today’s situation is different development of “neutralization technologies” for terminating the in key ways: firstly, scholars have documented how medical psychedelic experience and drug administration through novel professionals, regulators, and patient groups have pushed for target-controlled intravenous infusion techniques (20) suggest “pragmatic” and “adaptive” trial designs in the intervening to us that therapeutic practices will be developed that combine decades (14). Secondly, today’s psychedelic clinical researchers both “shutting down” and “opening up” to offer new options are self-consciously aware of, and keen to prevent, a return to psychedelic prohibition, carefully proffering a “sober objectivity,” for experiential manipulation, in line with the growing call for personalized medicine. and emphasizing psychedelics as therapeutic agents as opposed to subversive agents of social and political change (15). Thirdly, Psychedelic Therapy as Driving Interest in we suggest psychedelic therapy is well-suited to the growing calls for psychiatry to be more oriented to the relational (16). Suggestion Nevertheless, bubbles burst, and we offer four axes along Psychedelic therapy trials are generating data we suggest which to consider this in relation to psychedelic therapies. Firstly, could fruitfully be conceptualized through the framework critiques of psychedelic therapy trial publications have warned of of the sensitivity of therapeutic altered states to suggestion. common features of the RCTs that are likely to be inflating effect This connects several literatures: a tradition of psychedelic sizes: participant self-selection, stringent screening procedures, research that proposes the drugs produce states of heightened small sample sizes, and difficulty in maintaining blinding in suggestibility against a longer historical interest in hypnosis research trials (2). Secondly, as the therapies gain legitimacy, (21–24); psychedelics as psychoplastogens, increasing cognitive the psychedelic research community is itself changing. Until and emotional flexibility (25–27)); the field of placebo studies recently, this community has comprised researchers who were (28–30); ritual theory (31, 32) and the study of “common factors” willing to accept the professional ramifications of working across psychotherapies (33) alongside other process-oriented in a stigmatized area. While the early advocates of any new research into psychological change. By bringing these literatures treatment can be expected to be enthusiastic, the interaction into a fuller encounter, we imagine a range of conceptual effects of any researcher bias with psychedelics’ sensitivity to the distinctions, methodological considerations, and theories, context of their use would contribute especially large outcome animating new directions for psychedelic therapy research. confounders, leading to limited replication of the early findings. Considering the above literatures, it would be timely to bring Thirdly, we should anticipate a growth in adverse outcomes as together psychedelic researchers and experts in these related the hype grows, the participant/patient pool is widened, and areas, to identify trial designs and interpretive frameworks psychedelic therapies are provided in more streamlined ways. that support mutually fruitful lines of inquiry. Interdisciplinary Increasingly diverse patient populations hopeful of being cured research could reveal the processes by which the psychedelic will experience rocky “landings” post-treatment, the cost of experience may be “baking in” a particular message or self- which will be borne downstream of trial analysis end points, reorientation that has been primed or reinforced by the other thereby falsely inflating favorable health economic calculations. study components. Without wanting to foreclose what such Frontiers in Psychiatry | www.frontiersin.org 2 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy conversations will open up, we are particularly interested in two broadly, owing to how sensitive psychedelic experiences are to avenues of inquiry: firstly, more fully measuring the expectations the context of their use. Some researchers have called for more held by participants at different stages of the intervention would detailed measurement of the context of psychedelic therapy in reveal more than potential confounds within trials—it could order to better grasp its therapeutic mechanisms [cf. (38, 41, 42)], teach us about the looping effects of the bubble itself, by something the growth in survey approaches is endeavoring to indexing how trials are themselves differentially emplaced within do [e.g., (43)]. We wonder what it might mean to circumscribe a timeline of the evolving hype around psychedelic therapies. the generalizability of research findings much more narrowly, Secondly, a fuller engagement with placebo studies suggests the acknowledging not simply that there are additional contextual need to consider more fully the role of uncertainty, hesitation, parameters that need taking into account but that it may not be and doubt in healing through psychedelic therapy (31, 34), and possible to determine intervention effects in any general sense, how these are cultivated through drug-set-setting configurations given the plethora of “experimental contingencies” (2:8) in any that offer the opportunity to “[traffic] in human possibilities given context. rather than in settled certainties” (35). Reflections on the history The need for a more context-sensitive and systematic coupling of placebo studies may also caution against reprising politically of research pre- and post-approval is important. Psychedelic and ethically fraught attempts to identify the suggestible “type” therapies seek approval based upon safety and efficacy data, of person (Phoebe Friesen, personal communication). We worry, and yet their very approval may affect their efficacy and however, that such interdisciplinary enquiry is being sidelined in safety profiles, as mediated by expectations and understandings the rush to approve particular psychedelic therapy packages for of the substances borne of the evolving bubble that their the treatment of particular indications. hype is generating. Psychedelic therapies also challenge any easy separation of safety and efficacy, as when, for example, The Role of Care powerful new meanings and senses of purpose are generated A broad intersecting of psychedelic research and related research that are therapeutic, but only with appropriate structures of literatures also suggests a deeper valuing of the role of care support and care. Existing post-approval regulatory landscapes structures in psychiatric care writ-large. While the imperative are poorly equipped to meet the needs of patients for up- in placebo-controlled antidepressant trials has been to minimize to-date (re-)evaluations of safety and efficacy. Regulators lack the placebo response by limiting patient expectancy and comprehensive and timely data for determining post-approval therapeutic contact (36, 37), this is inverted in the enriched safety issues, much less changes in efficacy, and have failed to spaces and care protocols developed for psychedelic therapies enforce the surveillance measures they currently demand of the (38). These spaces and protocols challenge the reductionism of pharmaceutical industry (44). The shift in onus of responsibility psychopharmacological interventions by drawing attention to to patients and providers to deliver on what is called “post- the relational aspects of care, moving from a compartmentalized marketing surveillance” via reporting systems has largely failed focus on symptoms in need of treatment to a more holistic view to deliver, due to under-use and the constraints posed by of human suffering and the value of meaning-making in health imperatives for data anonymization (45). and wellness. More broadly, the rise of the psychedelic therapy One logical endpoint of the calls for greater context sensitivity bubble has contributed to the growing awareness of a wider and the ongoing monitoring of changing safety and efficacy ecology of healing practices that center the body, space-making, profiles is in the technically-mediated surveillance of psychedelic and spirituality. therapy through adjunctive devices and apps, as seen in calls However, the significant opportunities for psychedelic for the use of ever-more-granular monitoring technologies researchers to refocus psychiatric treatments on enriching in order to adequately power research (46). It remains to and optimizing relations of care is compromised by industry be seen whether such “field approaches” can provide useful pressures, including commercial incentives to foreground findings. Meanwhile, the normalization of such technologies the “drug treatment” model over the crucial (39) but costly raises substantial legal and political concerns, in particular psychotherapeutic work, and a regulatory system designed to around the case for reconsidering proprietary rights in relation evaluate the administration of drugs as stand-alone treatment to data capture. modalities. Emphasizing the relations of care that appear to us to be key to safe and effective psychedelic therapy will also require coordination across scales and disciplines. For example, DISCUSSION some psychedelic advocates are beginning to make the economic case for psychedelic therapies by appealing to the long-term In this opinion piece we have sought to foster greater critical cost-savings achieved if psychedelic therapies are considered a discourse around the broader regulatory, cultural and economic curative rather than a palliative care treatment [in relation to forces shaping psychedelic research. While we have argued for MDMA-assisted psychotherapy, see (40)]. It remains unclear the need to be attentive to how the psychedelic therapy bubble whether this strategy will persuade healthcare payers. is shaping its potential, we end on a note of optimism. In considering the “bubble” as a public health measure in the Regulatory Dynamism wake of the Covid-19 pandemic, Appleton (47) invites us to Finally, we suggest that psychedelic therapy research heralds an imagine bubbles as affording a protected space in the knowledge opportunity to rethink the regulation of drug research more that such a space is temporary. We might then consider Frontiers in Psychiatry | www.frontiersin.org 3 September 2021 | Volume 12 | Article 727050 Noorani and Martell Psychedelic Therapy Beyond the Dichotomy this moment an opportunity to develop robust methodologies therapy’s potential to re-invigorate Western psychiatry might be and alliances across research disciplines and with stakeholder better realized. groups, and to inquire into the most pressing research questions of psychedelic therapy, before the bubble bursts. For us, AUTHOR CONTRIBUTIONS these questions include greater consideration of the role of community support structures, psychedelic therapy’s long-term This manuscript emerged out of a series of conversations between effects, what “safety” and “efficacy” mean amongst different TN and JM, followed by the joint writing of the abstract. TN stakeholder groups, and how best to set up harm reduction led the writing of a first draft of the full manuscript. All authors services and infrastructures, all before driving forward the then redrafted the manuscript, together and independently, and mass scaling of pre-maturely-rigid formulations of psychedelic approved the submitted version. therapy. We recognize that this lies in tension with the imperative to scale, itself drawing on the language of a growing ACKNOWLEDGMENTS “mental health epidemic” and exacerbated by the Covid-19 pandemic. We maintain that by integrating the bubble’s shadow The authors would like to thank Albert Garcia-Romeu and before it bursts—or at least deflates [cf. (48)]—psychedelic Roberta Murphy for comments on an earlier draft. REFERENCES 17. Timmerman C, Watts R, Dupuis D. Towards psychedelic apprenticeship: developing a gentle touch for the mediation and validation of 1. Carhart-Harris RL, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, psychedelic-induced insights and revelations. Transcult Psychiatry. (2020) Murphy R, et al. 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