Abstract
Despite growing interest in psychedelic-assisted therapy (PAT) research, there remains a lack of consensus about key issues relevant to difficulties in predicting acute drug effects, and the role of therapeutic support in clinical trials. In the absence of a clear theoretical model to conceptualize multifaceted components in PAT research, dialogue across contexts (e.g., popular media, peer reviewed journals, conference settings) is becoming increasingly polarized and siloed. This has even contributed to somewhat unusual recommendations by the FDA and others that removing critical aspects of psychological and medical safety could enhance our ability to investigate the impact of these drugs on clinical outcomes. Considering the importance of determining and maximizing safety in ongoing PAT research, this commentary suggests that an ecological systems theory (EST) approach provides a structure to make contextual and practical factors a more explicit and testable component of research. Utilizing systems theory and Bronfenbrenner’s EST approach adapted for healthcare settings, we propose that a more detailed conceptual model in PAT research would enable more explicit consideration of contextual factors informing and influencing outcomes. This commentary is accompanied by a custom figure that illustrates application of this model for psychedelic research and highlights the limitations of current measurement of acute subjective experience.
Excitement is growing for novel mental health treatments emerging out of recent psychedelic research following a decades-long prohibition due to the Controlled Substances Act of 1971. Preliminary safety and efficacy of psychedelic-assisted therapy (PAT) has garnered interest among researchers and clinicians, as well as industry, policymakers, journalists, and the public. Despite the hype (Yaden, Potash, & Griffiths, 2022) and evidence, which suggests a new paradigm of mental health care (Yehuda & Lehrner, 2023), lack of consensus about key issues relevant to PAT trials warrants further consideration in order to generate actionable solutions.
One of these issues is the difficulty in predicting acute psychedelic effects. As Dr. Roland Griffiths said in response to a question from Anderson Cooper regarding psychedelics, “Our ability to predict [who is going to have a bad experience, who is going to have a transcendent experience] is almost none at all.” (CBS, 2019) Furthermore, there is scant evidence accounting for expectation of acute psychedelic effects by participants and session facilitators on treatment outcomes in PAT trials. Concerns about this have led the Food and Drug Administration (FDA) to suggest minimizing this issue by limiting involvement of session facilitators (U.S. Food and Drug Administration, 2023). However, reducing such psychological support may result in greater risks to participants. Therefore, we believe a more detailed conceptual approach that situates psychedelic drug administration within a broader theoretical context is needed to address these key issues, while strengthening our understanding of the infrastructure of therapeutic support needed in PAT trials.
The constructs of ‘set' (psychological mindset) and ‘setting' (environment) have been used to substantiate the need for supportive infrastructure in psychedelic trials, including the use of substantial psychological support and comforting environmental elements (Eisner, 1997; Johnson, Richards, & Griffiths, 2008). However, there have been few attempts to empirically validate this assertion. Here, we suggest utilizing systems thinking (Peters, 2014) and adapting an Ecological Systems Theory (Bronfenbrenner, 1974, 1979; Bronfenbrenner & Ceci, 1994) (EST) model for healthcare settings (Batt, Williams, Brydges, Leyenaar, & Tavares, 2021) as a testable model for PAT research. In our view, an EST approach provides a way to make the proximal and distal set and setting factors explicit in an attempt to account for what influences acute psychedelic effects. Thus, application of this approach would enable the creation of testable hypotheses for PAT studies.
Systems thinking: making models explicit
Models can help us represent objects and phenomena, and visually explain how things work. Because models aid us in processing information and deriving meaning, we tend to make mental models when thinking about a problem, or doing things like interpreting research, or providing patient care. The challenge is, such implicit models carry hidden assumptions, beliefs, and biases, preventing us from seeing the full picture. Systems thinking aims to make explicit models, to identify distinct parts contained within a system (including assumptions), to see how these parts connect to one another as a part of a greater whole (Peters, 2014). Explicit models also enable consideration of beliefs and assumptions informed by cultural differences across disciplines such as psychiatry, pharmacology, and psychology, that interface in the consideration of PAT.
Set and setting is an embedded assumption in psychedelic research. Given that emphasis has been placed on the importance of these factors in supporting safe experiences, without further definition of these assumptions, perhaps through a testable model, the understanding of the application of set and setting in PAT is limited.
Ecological systems theory
Bronfenbrenner originally conceived of the EST model as a theoretical approach for understanding human development, wherein the developing person and ecological context (environment) have a reciprocal relationship with bi-directional impact (Bronfenbrenner, 1974, 1979; Bronfenbrenner & Ceci, 1994). Envisioning EST as a set of concentric circles, each smaller one inside the next, Bronfenbrenner placed the person at the innermost center. Moving outward, this model makes explicit the ever-evolving process of interaction between the individual and varying levels of environment represented by the micro-, meso-, exo-, and macro-systems, enacted over time (chronosystem). Through this detailed conceptual model, one could more thoroughly investigate the impact of various levels of one's set and setting in predicting acute psychedelic effects. Furthermore, Bronfenbrenner (1974) asserted the critical importance of mutual interchange between social policy and empirical science, so that each informed the other. This seems particularly germane given the consideration of PAT for medical approval, and the incumbent need for regulators and scientists to decide under what conditions and for whom PAT will be available. These questions will require a robust model for understanding individual - environmental interactions relevant to PAT from a public health standpoint that we feel EST can help provide.
Adapting EST for PAT research: a participant-centered approach
Bronfenbrenner's model provides a useful framework to identify and differentiate interrelated factors influencing participant experiences in the context of PAT research (Fig. 1). Similar to application of EST for healthcare settings (Batt et al., 2021), the research participant's psychedelic experience could be influenced by socio-economic, cultural, and other factors embedded within the ecological environment.
Adapting an Ecological Systems Theory Approach for Psychedelic Research. Proposed adaptation of EST for psychedelic research depicting participant and facilitator in ecological environment
Citation: Journal of Psychedelic Studies 8, 3; 10.1556/2054.2024.00374
For example, we can identify influential factors at various system levels: at the person level (e.g., acute drug effects, participant's experience of mental health symptoms, trauma history); the relationship between settings (e.g., clinical trial study team, cultural norms about substance use, social support); broader research settings (e.g., IRB and study sponsors); even broader settings affecting the participant indirectly (e.g., FDA, DEA); societal influences (e.g., stigma about mental illness, stigma about psychedelic drugs, systemic racism, hype); and even global events at the broadest level (e.g., global pandemic, internationally endorsed priorities and values). Given the topological and bi-directional nature of the EST model, identifying these distinct yet interdependent components makes more explicit the various factors influencing the set and the extended setting in which the participant's psychedelic experience is situated. Likewise, the participant's psychedelic experience in turn informs the broader ecology on all levels.
Adding complexity: the impact of session facilitators
Utilizing EST to identify and differentiate interrelated factors relevant to a facilitator-centered model adds depth and complexity to our understanding of the PAT trial environment and what psychedelic effects may be experienced by participants. The flexibility of the EST model also enables identification of factors influencing or biasing the facilitator at various levels (Fig. 1).
Present and future ecologies
To concretize this proposed application of ecological systems theory and systems thinking approaches in psychedelic research, we are preparing to disseminate a preliminary explanatory sequential-design mixed methods study, beginning with a survey aimed at understanding individuals' sense of identity in relation to the world following a memorable drug experience. In addition to utilizing items from acute effect measures from psychedelic clinical trials (see Fig. 1) this survey will also employ instruments designed to capture details about identity, acculturation, as well as coping styles. These data will guide future research applying an ecological and transdiagnostic approach to case formulation and integration surrounding psychedelics. By bringing an EST approach to investigating the experiences and impact of psychedelic use, we hope to identify individual and proximal factors relevant to the safety and efficacy of PAT and learn more about how PAT can be refined further.
An EST approach to PAT research
It is hopeful to imagine new PAT treatments at the ready to meet ever-growing demands of taxed mental health systems worldwide in the aftermath of a global pandemic, ongoing social inequities, and the climate crisis. That said, present challenges within the field of psychedelic science are multifactorial and interdisciplinary. In absence of a model to conceptualize multifaceted components at this stage of development, dialogue across contexts (e.g., popular media, peer reviewed journals, conference settings) is becoming increasingly polarized and siloed. This contributes to somewhat unusual recommendations by the FDA and others (Goodwin, Malievskaia, Fonzo, & Nemeroff, 2023) that removing critical aspects of psychological and medical safety could enhance our ability to investigate the impact of psychedelic drugs on clinical outcomes despite evidence of the role of therapeutic alliance on outcomes (Levin et al., 2024; Murphy et al., 2022). It is our view that we should adapt our models to better understand, and measure, those effects within the context in which these treatments occur. Informed by systems thinking (Batt et al., 2021; Peters, 2014) the EST approach to PAT research presented here provides such a structure to make contextual and practical factors contributing to key issues an explicit, and testable, component of research. Additionally, the adapted ecological model presented here also has pedagogical implications for the training of future clinicians (Brymer & Schweitzer, 2022) and researchers in psychedelic science, as well as psychedelic-informed care for broader mental health and health care systems as a whole. Our view is that the collaborative and interdisciplinary application of this approach is critical to maximize patient safety while simultaneously enhancing empirical precision.
Author contributions
MAD developed the paper and diagram concept, wrote the original paper draft, and oversaw editorial and submission efforts; oversaw diagram creation and production with Dept of Transformation and Florian Brendel. AGR contributed to editorial and writing process and feedback. AKD contributed to editorial and writing process as well as feedback on diagram development. Dept of Transformation contributed to diagram production and Florian Brendel created diagram in collaboration with MAD.
Conflict of interest
MAD and AKD are supported by the Ohio State University Center for Psychedelic Drug Research and Education, funded by anonymous private donors. AKD and AGR are supported by the Johns Hopkins Center for Psychedelic and Consciousness Research, funded by Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. AKD is a board member of Source Research Foundation. AGR is a paid scientific advisor to Innerwell. AGR has received research funding from MicroDoz Therapy Inc., Mydecine Innovations Group Inc., Unlimited Sciences, the Council on Spiritual Practices, the Heffter Research Institute, and NIH. AKD is an Associate Editor of the Journal of Psychedelic Studies.
Acknowledgements
We thank the members of the Center for Psychedelic Drug Research and Education (The Ohio State University), along with Dr. Emma Morton (Monash University), and Dr. Clint Hougen (Icahn School of Medicine) for their feedback during concept development. Diagram design: Florian Brendel/Dept of Transformation.
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