This report (2022) explores the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy (PAP) in vulnerable populations. The authors propose that working with vulnerable populations requires special attention to their context. Recommendations for future research include an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building a therapeutic alliance, multicultural competence, and flexible study designs.
Psilocybin-facilitated psychotherapy shows potential transdiagnostic efficacy for a range of mental health conditions. Though vulnerable populations bear a disproportionate mental health burden, they have been largely neglected in the clinical psilocybin literature. However, if the field is to best respond to the diverse needs of individuals from vulnerable populations, care must be taken to ensure these individuals are represented in the empirical research. This report calls attention to this concern by detailing the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy in vulnerable populations. First, we show how working with vulnerable populations must be considered in the context of an often-problematic past and differential exposure to and experience with classic psychedelics. We then provide actionable recommendations for future research testing psilocybin-facilitated psychotherapy in vulnerable populations, including an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building therapeutic alliance, multicultural competence, and flexible study designs. On these premises we call for future work in this area, underscoring that there is vast room for improvement and expansion in this rapidly advancing field of study.
Ortiz and colleagues note that psilocybin-facilitated psychotherapy has accumulating evidence of efficacy across several mental health conditions, yet people from vulnerable populations—defined here as underresourced social groups at elevated risk for poor health outcomes—have been largely underrepresented in clinical psilocybin research. The Introduction situates this gap within broader calls for multicultural competence in mental health care, emphasising the importance of understanding patients' lived experience and provider identity when working with groups such as socioeconomically disadvantaged individuals, people experiencing homelessness, racial/ethnic minorities, sexual and gender minorities (SGM), older adults, people with disabilities or chronic conditions (for example, HIV), and people involved with the criminal justice system. This report, presented as an invited talk at the NIH Psilocybin Research Speaker Series, sets out to provide a concise primer on advancing culturally informed evaluation of psilocybin treatments in vulnerable populations. Rather than exhaustively treating any single group, the authors aim to highlight cross-cutting historical, ethical, methodological, and practical issues and to offer actionable recommendations to improve recruitment, assessment, therapeutic practice, and study design when working with these populations.
Papers cited by this study that are also in Blossom
Anderson, B. T., Danforth, A. L., Daroff, R. et al. · EClinicalMedicine (2020)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)
Family, N., Hendricks, P. S., Williams, L. T. J. et al. · Journal of Psychopharmacology (2022)
The extracted text does not report original empirical methods typical of a clinical trial or systematic review. Instead, the paper is a narrative, perspective-style report based on an invited presentation at the NIH Psilocybin Research Speaker Series. The authors synthesise historical context, prior literature, and experiential and ethical considerations to generate recommendations; they do not describe systematic search procedures, inclusion criteria, or formal data-analytic methods in the extracted text. Because this is a conceptual and practice-focused report rather than a primary dataset analysis, the ‘‘methods’’ consist of thematic exposition: establishing historical precedents, identifying barriers to inclusion, and proposing practical strategies for recruitment, measurement, therapeutic engagement, staff composition, and study logistics. The authors also reference prior empirical and community-based work to support recommendations, but the extraction does not present a formal appraisal or synthesis methodology.
There are no empirical results reported in the extracted text; instead, the authors present a set of findings from the literature and from their synthesis of historical and practical considerations. A central theme is historical context: classic psychedelics have long ritualised uses in some cultures but also a fraught institutional history in the West, including covert and coercive experimentation (for example, CIA involvement and administration to incarcerated people) and exploitative episodes that have undermined trust, notably the case of María Sabina whose sharing of psilocybin ritual knowledge led to harms for her community. These histories help explain current patterns of interest, mistrust, and underrepresentation among some vulnerable groups. The authors identify several practical barriers to including vulnerable populations in psilocybin research. Non-representative recruitment—often relying on convenience samples—tends to favour white, socioeconomically advantaged individuals who have positive expectancies from recent media coverage. Conversely, individuals or communities whose exposure has been limited to sensationalised negative narratives, or who have experienced exploitation by science or disproportionate harm from drug policy, may be difficult to recruit and retain. Cultural objections can also arise where classic psychedelics are sacramental or sacred in origin, and some communities may resist medicalisation or commodification of those practices. Measurement and communication challenges are emphasised. Many self-report instruments used to characterise psilocybin-occasioned experiences (for example, mystical-type scales) were developed in more highly educated samples and lack validation in vulnerable or multilingual populations. The authors recommend using accessible, non-esoteric language to describe likely subjective effects (for example, ‘‘profound awe’’ rather than exclusively ‘‘mystical experience’’) and developing multilingual, culturally sensitive assessment tools. They also advise respecting participants’ religious interpretations rather than dismissing them as merely neurological phenomena. Clinical-process recommendations focus on therapeutic alliance and preparation. Therapeutic alliance—here meaning the working relationship, trust, and rapport between participant and clinicians—should be prioritised because many vulnerable individuals carry histories of powerlessness, adversity, or maltreatment that can amplify distress during psilocybin experiences. The authors note that while a psychological stance of surrender can predict beneficial mystical-type experiences, preoccupation tends to predict challenging experiences; focused preparatory work and empathic support during acute effects are therefore important. The report also expects some participants will struggle during dosing sessions and recommends transparency and empathic response to those challenges. Workforce composition, cultural competence, and structural barriers are also covered. Incorporating scientists and staff from the populations under study may aid recruitment and make procedures more relevant, but the authors caution that representation alone does not guarantee better outcomes. Evidence from other domains shows mixed effects of racial/ethnic or gender matching between clients and therapists on outcomes and retention; by contrast, culturally adapted interventions and higher client ratings of therapist multicultural competence are associated with better process variables and, to a lesser extent, outcomes. The report highlights structural obstacles that limit diversity among investigators and suggests training and entry opportunities across study roles to broaden participation. Finally, practical trial-design adaptations are proposed to reduce participant burden and increase accessibility: flexible scheduling (evenings/weekends), reduced or more efficient session formats where feasible, partial use of mobile technology for psychotherapy and assessment, reasonable noncoercive financial compensation for time and expenses, leniency in rescheduling without penalising enrolment, and reconsideration of overly conservative exclusion criteria that disproportionately disqualify individuals with comorbid medical or psychiatric conditions common in vulnerable populations.
Ortiz and colleagues interpret their synthesis as a call to action: psilocybin-facilitated psychotherapy shows promise, but the field must attend to historical harms, structural barriers, and methodological shortcomings to meaningfully include vulnerable populations. They position their recommendations as preliminary guidance rather than definitive solutions, noting that each vulnerable group warrants more extensive, specific attention than the present broad overview affords. Community engagement is presented as a key mechanism for improving recruitment, retaining participants, and refining study methods and outcomes; the authors cite a pilot example in which community-adapted, psilocybin-facilitated group therapy for demoralisation among gay-identified AIDS survivors was successfully adapted with community input. The authors acknowledge several uncertainties and limits. The evidence base for many of their proposals remains nascent; measures of mystical or subjective experience lack validation in diverse and multilingual samples, and the causal impact of workforce diversity on treatment outcomes is mixed in prior psychotherapy research. They also note practical challenges to diversifying the research workforce, including that involvement in psychedelic research has historically posed career risks and that structural barriers limit access to advanced training for people from marginalised backgrounds. As such, representation is necessary but not sufficient—multicultural competence among clinicians and researchers is emphasised as critical, though how best to define, measure, and improve it is unresolved. In terms of implications, the report advocates for focused, community-partnered recruitment strategies; culturally and linguistically appropriate measurement and communication; prioritising therapeutic alliance and careful preparatory work; pragmatic adaptations to reduce participant burden; thoughtful, noncoercive compensation; and revisiting exclusion criteria that unnecessarily exclude people with common comorbidities. The authors recommend integrating individuals from target populations into research teams across roles and training pathways, while remaining realistic about the barriers and mixed evidence regarding matching or representation effects. Overall, they call for iterative research that refines and expands these ideas so that psilocybin treatment paradigms can be ethically and effectively evaluated in those who bear disproportionate mental health burden.
The paper concludes that while psilocybin-facilitated psychotherapy is a rapidly advancing area with therapeutic potential, vulnerable populations remain a blindspot in clinical research. The authors present this report as an initial overview and offer concrete recommendations—summarised in a table in the original document—to improve representation, measurement, therapeutic practice, and study design. They express hope that future work will refine these recommendations and broaden understanding of how to develop and implement psilocybin treatments for populations that experience disproportionate health burdens.
Burgeoning data indicate that psilocybin-facilitated psychotherapy may be effective in the treatment of a number of mental health conditions. Though vulnerable populations bear disproportionate burden of mental illness, these populations are conspicuously underrepresented in the clinical psilocybin research. The following report, based on an invited talk at the National Institutes of Health (NIH) Psilocybin Research Speaker Series, provides a brief primer on advancing multicultural competence in the evaluation of psilocybin-facilitated treatments in vulnerable populations and delineates the challenges and opportunities involved in working with these populations in this area of study. We acknowledge that extensive discussion could be dedicated to any one vulnerable population and aim here only to offer a broad overview of issues common across many of these populations. We encourage the interested reader to consult the references at the end of this report. Vulnerable populations are conceptualized as underresourced social groups at higher risk for poor health outcomes (e.g.,including but not limited to socioeconomically disadvantaged individuals, people experiencing homelessness, racial/ethnic minorities, sexual and gender minorities (SGM), older adults, people living with disabilities and chronic health conditions like HIV, and individuals in the criminal justice system (e.g.,. The role of multicultural competence in the provision of mental health services is a topic of increasing emphasis, with a focus on understanding patients' unique lived experience and reflecting on one's own identity to better appreciate provider-patient dynamics (e.g.,.
Though psilocybin and other classic psychedelics have been used by humans in ritualized contexts for millennia, the institutional application of classic psychedelics in the industrialized West had an inauspicious start in the middle of the 20 th century, with significant effort on the part of the Central Intelligence Agency (CIA) to weaponize these drugs. This effort involved the surreptitious administration of classic psychedelics to human subjects without their knowledge or consent. Furthermore, classic psychedelics were administered coercively to incarcerated people without therapeutic intent in a number of studies (seeand some investigations addressed the potential of classic psychedelics to address homosexuality (e.g.,, a view aligned with the dominant paradigm at the time that pathologized SGM individuals). Yet, naturalistic use of classic psychedelics became associated with the intelligentsia of the day (e.g., Aldous Huxley) and appeared to be largely accounted for by white individuals of higher socioeconomic status, a trend that appears to remain true today. This pattern comports with the notion that intentional classic psychedelic use in the contemporary United States is an experience more commonly afforded to those whose "deficiency needs" have been met (see, though cultural predilections may also account for these differences. There are notable exceptions to this trend, however. For instance, the use of peyote, a cactus that contains the classic psychedelic mescaline, and ayahuasca, an Amazonian admixture that contains the classic psychedelic dimethyltryptamine, have their origins in longstanding indigenous traditions in the Americas. Indeed, psilocybin was introduced to the Western world by María Sabina, a Mazatec healer who lived in a remote village in the Mexican state of Oaxaca. Sabina welcomed amateur mycologists R. Gordon Wasson, an American banking executive, and his wife Valentina, a Russian-American physician, to participate in a ritual involving the use of psilocybin mushrooms known as a "velada". The Wassons' excursions to Oaxaca were funded in part by the CIA J o u r n a l P r e -p r o o f. Sabina invited the Wassons to participate in the velada under the condition that her privacy was respected, and the location of her village was not published). Sabina's trust was violated in both regards upon the publication of the Wassons' subsequent works. The interest generated by the Wassons' efforts resulted in an unmanageable number of Western tourists flocking to Sabina's village, which in turn brought unwanted attention from law enforcement, making the already tense relationship between the indigenous community and police more fraught, in addition to desacralizing the ritual. Needless to say, this had a negative effect on Sabina's life, and she understandably regretted introducing the Wassons to the velada.
The current clinical evaluation of psilocybin should be conducted in light of this diverse historical context. Specifically, study rationales may be more acceptable to some groups than others. It would be expected to observe significant interest in participation from groups with positive psilocybin-related expectancies arising from vicarious or direct experience. Likewise, those with exposure to very recent media coverage framing classic psychedelics as game-changing treatments including bestselling books, network news television, National Public Radio, and podcasts (e.g., individuals of higher socioeconomic status) are likely to display significant interest. Conversely, recruiting and retaining participants from groups with limited exposure to classic psychedelics save for sensationalized narratives that prevailed from the late 1960s through contemporary times may prove challenging, especially considering that many such groups have a history of being exploited by the scientific enterprise (e.g., African Americans; Thrul & Garcia-Romeu, 2021). Additionally, cultural groups with a history of sacramental classic psychedelic use may object to the medicalization and/or commodification of a hallowed process (e.g., American Indians;. And it should not be surprising when, in vulnerable populations that have been disproportionately affected by the war on drugs, classic psychedelics are seen as just another substance associated with illicit markets, violence, and Draconian legal policy. These J o u r n a l P r e -p r o o f factors might explain, at least in part, why racial/ethnic minorities have not been well represented in the clinical psychedelic literature to date, and argue that research teams carefully consider how to best ensure representative samples. We propose that non-focused recruitment of convenience samples is insufficient. Rather, researchers should consider focused recruitment of vulnerable populations in close concert with community partners that serve the populations of interest, with attention to clear and transparent communication around study objectives and acknowledgement of the aforementioned historical trends. Beyond facilitating recruitment, community engagement can be used to solicit feedback on proposed methods and study outcomes. Such an approach was used with success in a recent pilot trial of psilocybin-facilitated group therapy in the treatment of demoralization among gayidentified AIDS survivors. Though this study was adapted to gay-identified men, psilocybin-facilitated treatments in SGM may represent an otherwise untapped area with significant potential to improve wellbeing. In fact, sexual orientation is not routinely reported in clinical trials of psilocybin (e.g.,, suggesting a missed opportunity to evaluate unique effects in SGM. A number of additional considerations warrant discussion. First, psilocybin's subjective effects are often characterized as ineffable. It is therefore incumbent upon researchers to inform participants of these effects in accessible language, such as explaining the experience as one of profound awe rather than framing it from the esoteric lens of mystical experience. This requires careful attention as unusually educated researchers-among the "weirdest" people in the world-are likely to encounter individuals with comparatively lower literacy levels when working with vulnerable populations. The assessment of psilocybin-occasioned experiences requires similar attention, as most self-report measures (e.g., the Mystical Experience Questionnaire;were developed by overly erudite academics and have yet to be validated among vulnerable populations. A related and obvious area of need is the development of multilingual self-report measures. Furthermore, acknowledging religious interpretations of psilocybin-occasioned experiences may be of J o u r n a l P r e -p r o o f particular importance given differences in religious orientation and religiosity across socioeconomic status and culture (e.g.,. Researchers should avoid trivializing religious experiences or attempting to explain them away as nothing more than neurological phenomena, as this would alienate religious individuals who may be more concentrated in some vulnerable populations. Second, distressing experiences of powerlessness may be a common thread among vulnerable populations (e.g.,. When evaluating psilocybin-facilitated treatments in such individuals we advocate that researchers avoid exacerbating these experiences and engage participants as equal partners with full agency. Though this maxim holds true for all research, it is particularly critical here because psilocybin can induce feelings of anxiety, panic, and paranoia. While a psychological state of surrender has been shown to predict beneficial mystical-type experiences with psilocybin, preoccupation has been shown to predict challenging experiences with the drug. Consistent with insights gleaned from the first wave of classic psychedelic research, we propose that surrender and preoccupation can be optimized among vulnerable populations when therapeutic alliance is prioritized (see, and in particular when themes of surrender are carefully addressed in preparatory sessions before psilocybin administration. Insofar that hardship, adversity, and maltreatment are daily realities for vulnerable populations in general-and especially in healthcare settings (e.g.,)-establishing therapeutic alliance may require dedicated time and specialized skills. Even with the utmost attention to therapeutic alliance, researchers should expect that some participants will struggle during a portion of the acute psilocybin experience (e.g., "What drug did they actually give me? What did they really do to me?"). Such struggle should be met with understanding and empathy both to mitigate immediate concerns and help participants benefit from challenging aspects of their experiences. Transparency regarding the expected range of subjective drug effects in language easy for participants to understand is strongly recommended.
Third, clinical psilocybin research should consider if and how the meaningful representation of individuals from vulnerable populations can improve research procedures and outcomes. Studies from other health domains employing community-based participatory research methods have long advocated for this and consistently underscore that doing so can help raise visibility to otherwise overlooked issues. The evidence base is still nascent, but growing, and suggests the meaningful integration of vulnerable populations is core to conducting impactful research and practice. One potential strategy to bolster representation could be to incorporate scientists and staff from those same populations, as opposed to the current status quo of studies being performed primarily by nonminority, socioeconomically advantaged researchers. Achieving this will not be without challenges. Engaging in psychedelic research has until recently been a risky career choice, which may have dissuaded a number of investigators from vulnerable populations from entering the field. Moreover, structural barriers often limit the ability of individuals from marginalized backgrounds to complete advanced education or obtain employment in the first place. Attention to the range of roles that it takes to complete research (e.g., recruiters, data collectors, and other study staff) can provide an initial entry point for individuals with less formal education, and with training over time, they can build on their personal experience to also include research expertise. Current metrics to evaluate the impact of integrating more diverse experiences have generated mixed results in the field of psychotherapy. Though clients generally prefer psychotherapists of their own race/ethnicity, this preference may not take high priorityand there is almost no effect on treatment outcomes from racial/ethnic matching of clients with psychotherapists. In addition, matching clients with psychotherapists on gender has demonstrated no or even negative effects on treatment retention (e.g.,, and gay and bisexual men clients' perception of their counselors' sexual orientation has not been shown to be related to process or outcome variables (e.g.,. In a similar vein, though it was once asserted that personal experience with a substance use disorder was essential to being an effective J o u r n a l P r e -p r o o f substance use counselor, this assertion has since been disproved. That said, culturally adapted interventions appear to be more effective for some racial/ethnic minorities than non-adapted interventions, and client ratings of psychotherapist multicultural competence are associated with more favorable process variables, and to a lesser extent, better outcomes. Of note, these findings hold true regardless of clients' racial/ethnic status, suggesting multicultural competence is a critical factor for all clients, not just those from vulnerable populations. Nevertheless, a discussion of how to best serve vulnerable populations is incomplete without an appeal to increase multicultural competence among all parties involved in a study, regardless of personal background. Unfortunately, whether multicultural competence is distinct from other therapeutic variables like empathy, and how to best improve multicultural competence, are poorly understood (see. In short, representation alone may assist with some important aspects of the research process (e.g., recruitment and retention), but is otherwise insufficient to ensure optimal outcomes. These findings underscore the continued need to advance our understanding of how to effectively integrate and assess the impact of meaningful representation of individuals from vulnerable populations in psilocybin research. Finally, as noted elsewhere) current psilocybin-facilitated treatment paradigms are time-intensive, rendering them difficult to access for vulnerable populations with limited resources and multiple competing demands. Researchers should consider how to best reduce participant burden while remaining flexible to deviations in study protocols. For instance, perhaps the number and length of sessions could be reduced without sacrificing therapeutic alliance (see, appointments could be scheduled outside of normal business hours (i.e., on evenings and weekends), and psychotherapy and assessment could be conducted partly via mobile technology. Furthermore, study participants could be given leeway to delay or reschedule appointments without jeopardizing their enrollment. Researchers should take into account financial incentives for J o u r n a l P r e -p r o o f participation that reasonably compensate individuals for time, transit costs, and other expenses such as childcare without being coercive or potentially attracting participants primarily interested in payment. Lastly, it may be prudent to deliberate on liberalizing exclusion criteria for participation, as the first contemporary psilocybin studies may have taken a more conservative approach out of an abundance of caution and with recognition of the heightened political lens surrounding classic psychedelics. This is relevant because a number of medical and psychiatric comorbidities disproportionately affect vulnerable populations, and consequently, their eligibility to participate in trials of psilocybin-facilitated psychotherapy.
In conclusion, psilocybin-facilitated psychotherapy has garnered renewed attention in recent years and shows promise as a treatment for a range of mental health conditions, prompting the NIH Psilocybin Research Speaker Series that included an oral presentation of the current report. Vulnerable populations are of special concern in this line of study despite being a blindspot in the clinical psilocybin research to date. The present report is conceived as providing an initial overview of this important area of inquiry. Recommendations for future research are summarized in Table. It is hoped that future research will refine and expand upon the ideas discussed here, leading to an enhanced understanding of the development of this emerging treatment paradigm among those who bear disproportionate health burden. J o u r n a l P r e -p r o o f
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Hendricks, P. S. · International Review of Psychiatry (2018)
Hendricks, P. S., Crawford, M. S., Cropsey, K. L. et al. · Journal of Psychopharmacology (2017)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Johnson, M. W., Hendricks, P. S., Barrett, F. S. et al. · Pharmacology and Therapeutics (2019)
Mertens, L. J., Preller, K. H. · Pharmacopsychiatry (2021)
Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychopharmacology (2019)
Smith, D., Faber, S., Buchanan, N. T. et al. · Frontiers in Psychiatry (2022)
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