Psychedelics in PERIL: The Commercial Determinants of Health, Financial Entanglements and Population Health Ethics

Abstract

The nascent for-profit psychedelic industry has begun to engage in corporate practices like funding scientific research and research programs. There is substantial evidence that such practices from other industries like tobacco, alcohol, pharmaceuticals and food create conflicts of interest and can negatively influence population health. However, in a context of funding pressures, low publicly funded success rates and precarious academic labor, there is limited ethics guidance for researchers working at the intersection of clinical practice and population health as to how they should approach potential financial sponsorship from for-profit entities, such as the psychedelic industry. This article reports on a reflective exercise among a group of clinician scientists working in psychedelic science, where we applied Adams’ (2016) PERIL (Purpose, Extent, Relevant harm, Identifiers, Link) ethical decision-making framework to a fictionalized case of corporate psychedelic financial sponsorship. Our analysis suggests financial relationships with the corporate psychedelic sector may create varying degrees of risk to a research program’s purpose, autonomy and integrity. We argue that the commercial determinants of health provide a useful framework for understanding the ethics of industry-healthcare entanglements and can provide an important population health ethics lens to examine nascent industries such as psychedelics, and work toward potential solutions.

Introduction

Psychedelic fungi, plants and plant-derived substances with psychedelic properties have been used for centuries by Indigenous communities for healing, pleasure and in various traditional practices. Since the 1960s, psychedelics have also been associated with counterculture and underground movements, primarily in the US. Research into the potential of psychedelics for mental illness and substance use disorders (SUDs) goes back at least to the 1950s but has been largely prohibited since the 1970s due to complex social, legal and political barriers including the Controlled Substances Act in the US and the US-led War on Drugs¹ (Dyck, 2006; The Lancet, 2006). Psychedelic therapies are enjoying a resurgence in mental health and substance use research due to an easing of some regulatory barriers and laws, shifting public attitudes, the lack of new psychopharmacological options in the psychiatry pipeline and researchers applying state-of-the-art scientific methodologies to examine psychedelic drugs (Belouin and Henningfield, 2018; Smith and Appelbaum, 2021). However, as this field unfolds, familiar challenges and risks with respect to the relations between industry and health research are coming into view. Indeed, as noted by Phelps, Shah and Lieberman (2022), ‘The first wave of psychedelic research was disrupted by conflict between cultural and political forces. The current wave of psychedelic research could be susceptible to an emerging conflict between entrepreneurial enthusiasm and scientific deliberation’.

As applied in contemporary clinical research and policy-making, the category ‘psychedelics’ typically connotes a group of compounds with different pharmacological properties, which can include psilocybin, lysergic acid diethylamide (LSD), mescaline, dimethyltryptamine (DMT) and related compounds (the ‘serotonergic psychedelics’, which act primarily via agonism or partial agonism at the serotonin 2A (5HT2A) receptor); ketamine (a dissociative anesthetic which acts primarily via NMDA receptor antagonism) and 3, 4-methyl enedioxymethamphetamine (MDMA, i.e. ‘ecstasy’, which is also classified as an ‘empathogen’ and which acts as a monoamine releaser and reuptake inhibitor, primarily dopamine and serotonin). Under appropriate conditions and at suitable doses, each of these compounds can produce a profound, nonordinary state of consciousness which, when paired with preparatory sessions and post-drug integration sessions, constitute a treatment modality referred to as psychedelic-assisted psychotherapy (PAP). The Food and Drug Administration in the US designated psilocybin-assisted and MDMA-assisted psychotherapy as Breakthrough Therapies in 2017 and 2019, respectively (Multidisciplinary Association for Psychedelic Studies, 2017; Saplakoglu, 2019). Despite the research being in a nascent phase, many researchers, policy makers and people who use psychedelics enthusiastically espouse their therapeutic benefits for mental illness and SUDs given their purported safety profile, rapid onset and robust and enduring psychological benefits (Belouin and Henningfield, 2018). Several jurisdictions in the US have attempted to decriminalize psychedelics, with Oregon recently passing legislation permitting access to psilocybin for mental health treatment (Phelps, Shah and Lieberman, 2022), and the Canadian province of Alberta becoming the first in the country to regulate the use of psychedelics for people in therapy (Cook, 2022). Australia recently became the first country in the world to legalize prescribing of both MDMA and psilocybin by authorized psychiatrists (Kisely, 2023).

The Emergence of the Corporate Psychedelic Industry

Several factors have made it challenging for researchers to access public funding for psychedelic research and drug development, including the illegal status of psychedelics in most jurisdictions, the societal perception of psychedelics as a threat to social mores and institutions, and a limited interest from the pharmaceutical industry in off-patent drugs. These challenges provided an opening for private philanthropy to fund research in psychedelics and to accelerate commercialization. For instance, there is a growing interest from investors, venture capital, and entrepreneurs into the potential of psychedelics for psychiatric illnesses such as depression and posttraumatic stress disorder (PTSD). At the same time, corporations that produce psychedelics have emerged as a multi-billion dollar industry. Psychedelic companies have grown in size and near market value akin to industries commonly known as Big Pharma and Big Tobacco. Some predict that the psychedelic market value will be worth close to $11 Billion USD by 2027 (PR Newswire, 2021). The psychedelic industry appears to be following the Big Pharma model, which focuses on marketing products that are patented and prescribed medications administered in healthcare settings, rather than following the path of cannabis, another relatively new legalized industry in Canada and some US states, which has focused on broad retail availability (Dean, 2021; Love, 2021). For example, anticipating therapeutic approvals, companies are attempting to secure patents for synthetic formulations of psilocybin compounds, as well as the room and manner in which psilocybin is administered (Basky, 2021; COMPASS Pathways, 2021; Marks and Cohen, 2021).

The Commercial Determinants of Health and Healthcare-Industry Relationships as a Population Health Ethics Issue

The commercial determinants of health (CDoH) are ‘factors that influence health which stem from the profit motive’ (West and Marteau, 2013: 686). The CDoH focus on the relationships between health and for-profit actors and their impact on population health (Maani, Petticrew, and Galea, 2022; Freudenberg, 2023). Historically the discourse surrounding CDoH has focused on ‘unhealthy commodity industries’ and the associated rise of noncommunicable diseases (Lee et al., 2022; Freudenberg, 2023; Gilmore et al., 2023). Scholars have argued that the CDoH are related to the social determinants of health (SDoH), as commercial factors can be considered one of many social factors that shape health. A narrow focus on the CDoH can provide a focus on which specific policy goals and solutions can guide action (Freudenberg, 2023).

It is well established that the practices of the tobacco, food, and pharmaceutical industries have contributed to health risks, threats to research integrity, and interference in policy processes (Wiist, 2010; Freudenberg, 2014; Marks, 2019). Studies of these industries suggest that they lobby to oppose regulatory controls that do not favor their interests and that they promote practices such as industry self-regulation, industry-supported public education, and individual (as opposed to corporate) responsibility (Lyness and McCambridge, 2014). Actors within these industries frequently seek out partnerships with government agencies, nongovernmental organizations, and academic researchers to influence the regulatory and policy environment and priorities for scientific research (Gilmore, Savell and Collin, 2011; Adams, 2016). Corporate actors across industries have consistently engaged in the conduct, sponsorship, and dissemination of scientific research to generate evidence that is favorable to their products; promote a desired policy and regulatory environment, and suppress or generate controversy regarding unfavorable research (Bero, 2005; Oreskes and Conway, 2011). Accordingly, deep financial relationships may contribute to misuse of evidence in healthcare (Moynihan et al., 2019). Industry sponsorship may also serve to shift research agendas in directions that may, knowingly or unintentionally, be harmful to public health (Goldberg, 2016; Fabbri et al., 2018). Compared to nonindustry sponsored messaging, industry sponsored messages tend to downplay risks of the product by increasing uncertainty about risks (Maani et al., 2022). Indeed, financial conflicts of interest (COI) may be associated with an increase in safety issues for drug products (Graham et al., 2022). Systematic reviews of studies across various industries and fields of research demonstrate an association between industry sponsorship and research outcomes that are favorable to the sponsor (Bes-Rastrollo et al., 2013; Mandrioli, Kearns and Bero, 2016; Lundh et al., 2017). These practices have led to issues such as publication bias and financial COI, the ethical importance of which has been documented extensively (Institute of Medicine, 2010; Brody, 2011; Krimsky, 2013). While industry contributes to societal welfare through technological innovation and the provision of products that are essential to health (Gilmore et al., 2023), many of the industries and their corporate practices identified in this section can be considered, by epidemiological standards, adverse to public health (Goldberg, 2016, 2018). This places the activities of the for-profit psychedelic industry—and the commercial determinants of health more broadly—in the domain of population health ethics (Krimsky, 2013; Goldberg, 2016).

The For-Profit Psychedelic Sector as a Case Study

Despite the vast amount of evidence of population health harms associated with industry–healthcare relationships, financial entanglements with various industry actors remain endemic (Chimonas et al., 2021). The for-profit psychedelic sector provides a useful case study given its recent emergence, along with anticipated regulatory approvals in many jurisdictions. The cannabis industry, also recently legalized, has begun to engage in similar corporate practices such as the financial sponsorship of scientific research (Grundy et al., 2023). At present, the for-profit psychedelic sector appears to be engaging in practices related to financial sponsorship like their corporate peer industry counterparts. For example, there are reports that donor interests—philanthropic, philanthrocapitalist and corporate—are shaping psychedelic research agendas at major academic centers (Gunther, 2022), and a recent article identified that the presence of COI in psychedelic literature poses a problem for evaluating the quality and scientific rigor of psychedelic research on mental health (van Elk and Fried, 2023). Nonprofit philanthropic funding tends to influence research priorities based on myriad factors independent of disease burden—and often those of primary interest to the donor (Best, 2012). Likewise, philanthrocapitalist donations apply market-based strategies to philanthropic goals to achieve a return on investment over the long term (McGoey, 2012). This matters ethically as corporations and philanthrocapitalist donors with an interest in investing in or developing products that can be commercialized can, through funding relationships, steer research agendas away from those that are in the primary interest of public health (Fabbri et al., 2018). For instance, Noorani (2019) argues that psychedelics’ research renaissance has always been directed toward the possibility of medicalization through commercialization by constructing psychedelics as medications² that can be marketed in high-income countries (Dorsey et al., 2009). Indeed, the private sector tends to fund research that will translate into an economic return on investment and has attempted to fill the funding gap left by the scaling back of public research dollars (Dorsey et al., 2010).

Bioethics has begun to explore ethical issues related to psychedelics research and treatment, with recent scholarship focused on issues such as ethics and policy (Smith and Appelbaum, 2022), clinical ethics issues such as ego dissolution (Smith and Sisti, 2020), informed consent (Gearin and Devenot, 2021; Jacobs, 2023), off-label promotion (Wexler and Sisti, 2022) and practices such as psychedelic-assisted psychotherapy and medical assistance in dying (Rosenbaum et al., 2023). Others have explored research ethics considerations (Kious, Schwartz and Lewis, 2023; McNamee, Devenot and Buisson, 2023), and the role of psychedelics and population health equity (Rea and Wallace, 2021). Matters relating to psychedelic industry–healthcare relationships have received some attention in general public-facing writing (Normand, 2020), and some organizations have produced their own guidelines focused on ‘ethical sponsorship and transparency’ for psychedelic conferences (Chacruna Institute, 2022). Noorani furthermore describes ‘a deep disappointment and anger’ (Noorani, 2019: 35) in the psychedelics community toward the activities of for-profit psychedelic companies and the lack of commitment to the principles of open science and open praxis with psilocybin, MDMA and other substances (Council on Spiritual Practices, 2021).

While many academic and healthcare institutions have adopted policies to help manage relationships with private industry, given the current increasingly scarce public funding context and precarious academic labor markets, many scientists within publicly funded organizations cannot realistically forgo all (or even any) financial relationships with the private sector, philanthropic or otherwise. This structural problem puts many scientists and their associated publicly funded academic healthcare organizations in a difficult position. This is especially so when scientists are faced with the decision to accept financial sponsorship from various corporate actors associated with so-called ‘dirty money’ or ‘morally tainted’ donors—for instance, money obtained in a manner that directly or indirectly harmed others (Tasimi and Gross, 2020). Aside from outright refusal and standard management strategies such as disclosure, there is limited ethics guidance for researchers who work at the interface of clinical practice and population health and within publicly funded and non-for-profit organizations to help them decide whether it is ethically defensible to accept money from industry sources and whether it is possible to minimize the risks these financial relationships may generate.

Methods

The following analysis reports on a reflective exercise undertaken by a group of clinician scientists involved in psychedelic research at an academic hospital in a large Canadian city. Anticipating the need to raise private funds to support their research program, the clinician scientists wanted proactively to develop a substantive and procedural ethics process to address questions about potentially accepting financial sponsorship from various corporate entities. Given the clinician scientists’ program of research on psychedelics, the group decided to focus on the growing for-profit psychedelic industry. The industry includes a spectrum of actors such as philanthrocapitalists, venture capitalists and startups, private equity firms, privately held companies and corporations. The first author of this article, a bioethicist and scientist, led the group in a series of meetings (8 hours in total) which took place via video call in summer 2021. The group explored a fictionalized case where an entity within the for-profit psychedelics industry wants to financially sponsor a psychedelic research program at an academic hospital (hereafter referred to as ‘the Program’) in some capacity (the group did not have a specific corporate or philanthropic donor in mind). This could be sponsorship of the research itself (e.g. funding a clinical trial), salary support, an education program, or a named research chair. The first author structured the discussion around the domains of the Adams (2016) PERIL ethics framework (Purpose, Extent, Relevant harm, Identifiers, Link; see below and Table 1), which was applied to the fictionalized case. Meeting minutes were collected and subsequently synthesized and interpreted by both authors.

Table 1.

Summary PERIL indicators applied to a fictionalized for-profit psychedelics case

Risk indicator	Description	Example
Purpose	Extent to which the primary mission of an organization clashes with the primary mission of an industry or philanthrocapitalist donor	• A psychedelic pharmaceutical company which develops and patents psychedelic & related medicines for commercialization
Extent	Extent, or perceived extent, to which an organization’s funding comes from this industry source	• The for-profit company proposes a donation that would cover, e.g. ~50% of a scientist’s research program’s operating costs
Relevant Harm	Degree of harm associated with this form of consumption	• Harms, both physical and psychological, that could potentially arise at individual and population levels from the product (i.e. psilocybin) or from the intervention (e.g. broader therapeutic approach) in which psilocybin is used
Identifiers	Degree to which the recipient is visibly identified with the funder	• Identifiers could include naming of an endowed chair
Link	Nature and directness of the link between recipient and donor	• Member of company sits on a researcher’s scientific advisory board for a randomized control trial involving psychedelics • ‘Restricted’ vs. ‘unrestricted’ grants

Design: PERIL Ethical Decision-Making Framework

Drawing from studies of the tobacco, alcohol and gambling industries, Adams provides evidence that these legal industries generate a disproportionate amount of their profits from people who consume their products. Adams (2012) argues that industries that produce what he calls ‘legalised addictive consumptions’³, such as alcohol, tobacco and gambling, differ in both their capacity to generate harm and their capacity to generate profits. For instance, the profits generated by these industries are then invested into activities designed to promote further consumption or to advocate for a policy and legal climate that is favorable to the company’s interests. When researchers, clinicians, policymakers, or publicly funded healthcare organizations enter into financial relationships with these industries, Adams argues that the partnership contributes to continuing demand for further profits. Such relationships can also foster financial dependency on industry sponsorship, which often results in a culture of silence and the promotion of government and regulatory indifference towards the resultant harms. In doing so, Adams suggests that these individuals and organizations, despite their good intentions, enter ‘moral jeopardy’ which risks loss of their purpose, autonomy and integrity. Other scholars have applied PERIL to conduct analyses regarding researcher relationships with the alcohol industry, pharmaceutical companies and other funding agencies (Miller et al., 2017).

PERIL is structured by the following domains: first, the Purpose refers to whether the primary mission of the recipient organization (e.g. an academic hospital) conflicts with the primary purpose of the sponsor (e.g. for-profit psychedelic corporation). Second is to determine the Extent to which the recipient (e.g. an individual researcher) relies on funds, for example, as salary support or research and operating costs. Third is the Relevant harm, which can be assessed as the degree of harm generated by consumption of the substance (e.g. evidence of harm from substances such as tobacco and alcohol); fourth is Identifiers, defined as ‘observable cues that signal the existence of an industry-funding relationship’ (e.g. branding); and finally, the relevant factors related to governance risk are the perceptions of reliance on these funds within the organization and also the directness of the Link between the sponsor and the decision-making apparatus of the organization.

Results: Moral Jeopardy Analysis

We structured our analysis based on the domains of moral risk as identified by Adams, which we have graded on a continuum from very low to extremely high moral jeopardy: ethical risks, contributory risks, reputational risks, governance risks, neutrality risks, relationship risks, and democratic risks. The degrees of risk are summarized in the supplementary materials.

Ethical Risks

An ethical risk emerges when a person or organization accepts money to achieve good from a source that does harm (Adams, 2016). Harm can be thought of in different ways, including physical and psychological harms (e.g. morbidity and mortality) as well as harms that are cultural and historic. An important consideration that follows from accepting money from the for-profit psychedelic sector is that the researcher becomes entangled in an ethical tension: how can a researcher or research program within a publicly funded academic teaching hospital that intends to serve the public good maintain their credibility when part of its financial support contributing to knowledge generation is derived from an industry that has caused harms to communities, including some communities that it serves? For example, there has been considerable criticism of the psychedelic industry culturally appropriating and profiting off of various Indigenous knowledges and practices, while many Indigenous communities remain excluded from the financial benefits of the psychedelic industry, as well as being harmed disproportionately by the War on Drugs under prohibition (Fotiou, 2019; Gerber et al., 2021; Devenot, Conner and Doyle, 2022).

Applying the Ethical Risk domain to our analysis, the group identified that the PERIL indicators of Purpose and Relevant harm apply to these considerations. The group identified a medium clash between the purpose of a for-profit psychedelic company, whose primary interest is profit and the primary purpose of a psychedelics research program at a publicly funded hospital, which is to generate evidence to improve patient care. This does not mean that a for-profit psychedelic company is not interested in patient care or promoting patient well-being, but rather these interests are of lesser priority than a corporation’s primary purpose, which is to generate profit (namely, obligation to shareholders or investors).

In terms of relevant harm, the group did not consider psychedelics as a harmful product in the same way that they would consider alcohol and tobacco a harmful product at the population level given the latter’s disproportionately negative impact on the global burden of disease and mortality (Nutt et al., 2010; GBD 2016, 2018, 2019, 2021). Indeed, while research suggests that the serotonergic psychedelics (i.e. those that act via the serotonin system, such as psilocybin and LSD) have low ‘abuse’ potential and adverse physical and psychological experiences are rare under appropriate conditions, risks such as hypertension, enduring psychosis and ‘bad trips’ outside of clinical trials are not well understood (de Wit, Bershad and Grob, 2021; Noseda et al., 2021). MDMA use also carries risks such as hyperthermia and seizures, in addition to risk of cardiovascular events as well as adverse psychological events and behavioral risks (National Institute on Drug Abuse, no date).

However, the relevant harm of the product need not apply to the substance only. For instance, the harm may depend on the type of psychedelic company and what they produce, for example, whether the company promotes their product(s) beyond indications for which there is evidence of effectiveness, safety and where benefits outweigh risk of harm; engages in questionable nonevidenced based therapeutic practices; or whether the company has a history of abuse or exploitation of clients or research participants (Normand, 2020; New York Magazine, 2021). Similar harms may arise if the company also owns for-profit psychedelic clinics that provide psychedelic therapies for indications beyond those approved by regulatory agencies, doses of a substance not supported by the evidence; staffed by unqualified and unregulated nonmedical professionals (Noorani, 2019; Smith and Appelbaum, 2021); or where the emerging standards of professional practice in this field are not met (e.g. sub-standard screening or accompanying psychotherapy). Furthermore, the process of medicalization—and the associated hype (Yaden, Potash and Griffiths, 2022)—may increase some of these risks. The psychedelic industry has every incentive to promote these still-experimental interventions as cutting-edge treatments and to market their products to as many consumers as possible. Marketing and promotions of psychedelics are further backed by the social authority and resources of biomedical science, which may provide some confidence that psychedelics—including unregulated versions—are safe for the treatment of mental illness and substance use disorders because they are identical to those used by regulated medical professionals. These dynamics may lead desperate people to seek out psychedelics in both medicalized and nonmedicalized/unregulated spaces to alleviate their suffering, including by members of populations with certain risk factors that make them poor candidates for psychedelic therapy. These risks may be further intensified for members of structurally disadvantaged populations who do not have the financial resources to access mental healthcare by regulated professionals.

Contributory Risks

Adams describes a contributory risk occurring when accepting financial sponsorship either indirectly or directly contributes to the sales of the product. Indirect contributions might occur when the funding relationship is used by the company to enhance their positive public profile or minimize negative public perceptions of the company. A direct contribution might occur when the consumer’s awareness of the funding relationship leads to increases in consumption. For instance, sponsorship of sporting events is an effective and longstanding approach to increase consumption of products such as alcohol and tobacco; research has shown a positive relationship between alcohol industry sponsorship of sporting events and alcohol consumption, including increased level of drinking amongst school-aged children and hazardous drinking amongst adults (Brown, 2016).

In our fictionalized example, the corporate sponsor is likely to benefit from the visibility of the relationship with a researcher through acknowledgements in funding statements in academic publications, presentations and websites. This may be considered a form of indirect advertising. Similarly, commercial interests in psychedelics may encourage the view amongst various publics that psychedelics are harmful when consumed in nonmedicalized settings, but pose low or minimal risks to the individual consumer when prescribed by regulated health professionals (Smith and Appelbaum, 2021); this ‘medicalization’ route serves commercial psychedelic interests with a strategy of patenting and marketing drugs which are prescribed in healthcare settings. The relationship may also benefit the psychedelic company if, for example, the company also owns for-profit psychedelic clinics and the positive image generated by the relationship drives business to such clinics. Accordingly, the group identified a strong clash of Identifiers and Purpose.

Reputational Risks

A scientist accepts a certain degree of reputational risk from negative perceptions of the industry relationship held by stakeholders, such as fellow researchers, patients, the ‘psychedelics community’ (including, but not limited to, shamans, Indigenous healers, psychonauts, and artists as identified by Noorani, 2019), and other publics.

The group imagined a high degree of concern, both from a patient/public perspective as well as professional perspective, if the funding for an academic research program focused on psychedelics came primarily from a for-profit psychedelic company. They were additionally concerned that the integrity of the research, as well as of the clinicians and scientists themselves, might be questioned over the long term even if a scientist receives a one-time donation of funds from a for-profit psychedelic company in the form of research operating costs, salary support, healthcare professional education, or learner stipends. Regarding the protection of trainees, the group highlighted the aims and standards for learners within the affiliated medical school, which include, for example, limits on the kinds of contact learners might have with industry representatives as well as the supervision and guidance learners ought to receive from faculty mentors in relation to industry (Faculty of Medicine, University of Toronto, 2019).

The group reasoned that high degrees of Purpose, Identifiers, Link and Extent may affect the willingness of stakeholders (e.g. patients, families, clinicians, learners, the psychedelics community) to place trust in the Program’s ability to maintain patient welfare as of primary importance over the competing financial interests of the sponsoring company. The impact of the reputational risk will depend on the specific public, as well as the extent to which the Program relies on the for-profit psychedelic company for funding.

Governance Risks

Governance relates to the capacity for independence and self-determination in research decisions. If a disproportionately high percentage of a scientist’s program of research funding comes from a for-profit psychedelic company, it may have an undue influence on the Program’s activities, such as the creation of research directions that align more with the company’s interests than public need or the Program’s interests and values. The influence on governance may arise both indirectly, through a high degree of sponsorship of research activities, as well as directly through membership on governance boards such as scientific advisories (i.e. company representatives might wish to sit on the Program’s advisory board). We identified extremely high degrees of Extent and high degrees of Identifiers and Link (see Table 1) that may compromise the Program leadership’s ability to act autonomously. The Program’s obligation to act in the interest of public health may also be unduly influenced by the interests of industry; this aspect was identified as high risk.

Neutrality Risks

Neutrality risks may affect the ability of the Program’s researchers, educators, and clinicians to provide services that are not shaped by industry interests. With financial sponsorship it may be difficult for members of the Program to remain neutral regarding a specific psychedelic corporation and its products (Adams, 2016). Erosion of neutrality may arise in several ways, one of which is the likelihood of fraternizing with industry representatives at official Program or hospital-related functions. It is in the interest of industry representatives to build positive relationships with Program staff, potentially extending the relationship through offers of socialization at nonhospital related events. Such relationships often cultivate a powerful sense of reciprocity, which may not be recognized by clinician researchers themselves. Indeed, while some clinicians, scientists and hospital administrators may claim that existing conflict of interest management strategies, including professionalism standards, are sufficient to ward off undue influence (White, Vaccaro and Zdeblick, 2007; Goldberg, 2015), the impact on neutrality naturally extends to other areas of the PERIL framework, such as Reputational, Governance, Relationship and Democratic Risks.

Threats to neutrality could affect the ability of learners, patients, and families to place trust in the Program’s ability to provide care that prioritizes their interests; after all, healthcare professionals have a duty to act in the best interests of patients and make clinical decisions free from undue influence (e.g. commercial bias). We identified extremely high degrees of Extent and Link and high risk of Identifiers and Purpose (Table 1), which may considerably affect the Program’s ability to remain neutral in all its activities. This is a high to extremely high-risk probable outcome.

Relationship Risks

Industry funding, no matter the extent, can affect professional relationships with colleagues both within and external to an organization. The group suggested that accepting psychedelic industry funding may create tensions within the Program, or within specific research teams. For instance, some research staff (e.g. research assistants, coordinators) who oppose industry sponsorship of research on ethical grounds may feel they do not have the power within the group to speak up against the financial sponsorship. This could create conflict within research teams and may disproportionately affect learners and early career researchers (Holloway and Herder, 2019). The decision to accept psychedelic industry funding may be publicly (and privately) criticized by colleagues, thereby impacting other potential academic relationships that clinician scientists may wish to cultivate. Some group members stated that because for-profit sponsorship of research is normalized in psychedelic research, and much of lab-based research in general, the impact of industry sponsorship on professional relationships may not be so negative; while some colleagues might not want to associate with researchers who accept funds from the psychedelic industry, others may see this as a nonissue, and some may see the financial relationships as a positive because of the researchers’ ability to attract external funding (Adams, 2012).

Clinical relationships with patients and families may also be at stake, as well as relationships with learners. As has been written elsewhere, financial relationships with industry can affect public trust (Institute of Medicine, 2010; Cain and Banker, 2020) along with perceptions of trustworthy evidence (Goldenberg, 2021). Accordingly, strong clashes of Extent,Identifiers and Link (Table 1) may lead to strained or potentially terminated professional relationships with colleagues inside and outside of the host organization, which has collateral implications for trust. We considered this a high-risk dimension.

Democratic Risks

Democratic risks pertain to democratic systems and tend to be more subtle and emerge over longer time periods. In the present example, the continued establishment/legitimizing of for-profit psychedelic clinics may contribute to the erosion of publicly funded healthcare in Canada and elsewhere, and continued under-funding of mental healthcare. A for-profit psychedelic funder may strongly oppose members of the Program it sponsors publicly advocating for policy changes (e.g. national pharmacare) that may go against the interest of the funder in medications that can be commercialized. Such conflict could potentially influence ongoing financial support of the Program. A for-profit psychedelic company—which has a strong stake in the profits from psychedelics—is unlikely to fund research endeavors or institutions that would go against their messaging or threaten their profits (Adams, 2012). This may result in loss of funding to the Program, or threats to withdraw funding if members of the Program express opinions perceived as threatening to the funder’s bottom line. There is evidence that the food industry uses financial sponsorship of research as a priority-setting process that privileges topics that align with its legal, policy and regulatory preferences (Fabbri et al., 2018). This process directs focus away from so-called inconvenient research that has the potential to cast a negative light on industry practices or its products. We identified strong clashes of Extent,Identifiers and Link and high risk of Purpose (Table 1). These clashes may affect the public’s trust in the Program to be motivated by public need rather than profit, and to resist potential pressure from the industry funder not to participate in educational or policy efforts which advocate for publicly funded mental healthcare and pharmacotherapy.

Discussion

In this article, we provided an ethics analysis through the lens of the CDoH of a fictionalized case of a for-profit psychedelic company that wants to financially sponsor clinician scientists and/or research programs in the evolving field of psychedelic science. We applied Adams’ PERIL framework to identify risks of moral jeopardy and what degrees of risk might be considered acceptable to maintain positions of scientific and ethical integrity.

Our analysis (Table 2) suggests that the probable risk outcomes associated with our case study occur on a continuum from low to extremely high moral jeopardy. In our analysis, risk dimensions were weighted heavily in the high to extremely high-risk dimensions. We identified a medium clash between the primary purpose of the for-profit psychedelic company (i.e. maximization of profit to satisfy obligation to shareholders), with the primary purpose of a nonprofit psychedelics research program at an academic health sciences center (driven ultimately by the delivery of care to patients in their best clinical interests). For Ethical Risk considerations, we identified low concerns about the relevant harm of psychedelics as it pertains to psychedelics as a broad class of substances. However, we also argue that psychedelics could be elevated to a moderate risk when considering the potential harms associated with (corporate-driven) hype amid the medicalization of these substances for certain populations, such as people at risk of psychosis. The group described high Contributory Risks, including a strong clash of Identifiers and Purpose in accepting money from a for-profit psychedelic company. We identified high degrees of Reputational Risks related to Purpose, Identifiers, Link and Extent that may affect stakeholders’ willingness to place trust in the Program’s ability to maintain patient welfare as primary. Governance risk considerations were high, as we identified extremely high degrees of Extent and high degrees of Identifiers and Link that may limit the Program’s ability to act autonomously. Neutrality Risks ranged from high to extremely high risk, as we identified extremely high degrees of Extent and Link and high risk of Identifiers and Purpose dimensions. The Relationship Risks dimension was similarly high risk, with strong clashes of Extent, Identifier and Link that may compromise professional relationships with colleagues who both support and do not support industry relationships. We did note, however, considerable conceptual overlap in the Relationship Risks and Reputational Risks domains of PERIL. Our analysis suggests that many of the Relationship Risks are perhaps mediated in part by the potential reputational harm that industry sponsorship may bring about in some cases. Lastly, we identified strong clashes of Extent, Identifiers and Link, and high risk of clashes with Purpose regarding Democratic Risks.

Table 2.

PERIL analysis summary

Risks	Context	PERIL indicators	Probable outcome
Ethical	• A researcher accepts money from a for-profit psychedelic company with the goal to conduct research on how to provide patient care (including with novel therapeutic agents) and education	Medium clash of Purpose, Extent andIdentifiers of for-profit companies whose primary interest is profit where the primary interest of the research program is patient care	Moderate risk
Contributory	• The psychedelic company benefits financially from a visible relationship with a clinician scientist at a high-profile academic hospital	Strong clash of Identifiers and Purpose in being linked to a for-profit company.	High risk
Reputational	• High degree of public and professional concern that funding of an individual researcher comes from a for-profit company	High degrees of Identifiers, Link and Extent may affect stakeholders’ ability to place trust in the ability of researchers to hold patient welfare as of primary importance.	High risk
Governance	• If a high percentage of research funding comes from an industry donor, it may have a disproportionate influence on the broader research program’s activities	Extremely high degrees of Extent and high degrees of Identifiers and Link may compromise a clinician scientist’s ability to act autonomously and create an independent program of research.	High to extremely high risk
Neutrality	• May affect the ability of the researchers, educators and clinicians to provide services that are not shaped by industry or donor interests • Could affect the ability of learners, patients and families to place trust in the scientist’s research program’s ability to conduct research that prioritizes—and protects—their interests • The researcher may be in a conflict if advocating for public policy re: psychedelics as medicines	Extremely high degrees of Extent and Link, and high risk of Identifiers and Purpose, may considerably affect the ability of researchers to remain neutral in all of their activities.	High to extremely high risk
Relationship	• Industry funding, no matter the extent, is likely to affect professional relationships with colleagues • Other relationships that may be at stake include clinical relationships with patients and families as well as learners	Strong clashes of Extent,Identifiers and Link, may lead to strained or potentially cessation of professional relationships with colleagues inside and outside of the host organization.	High risk
Democratic	• The continued establishment/legitimizing of for-profit psychedelic clinics may contribute to the erosion of publicly funded healthcare in Canada, and continued under-funding of mental healthcare • An industry funder or donor may strongly oppose researchers it supports advocating for policy changes (e.g. national pharmacare) that may go against the industry funder’s interest in for-profit medications, resulting in reduced funding to the researchers or their affiliated program	Strong clashes of Extent,Identifiers and Link, and high risk of Purpose. These clashes may affect the public’s trust in the researchers to not be motivated by profit; pressure from the industry funder to not participate in educational or policy efforts to advocate for publicly funded mental healthcare and pharmacotherapy.	High risk

Corporations exist primarily to pursue profit, so it is not surprising that a recently or soon-to-be legalized industry that has generated considerable excitement and a high market value would be interested in engaging in corporate activities like their peer industry counterparts. While our analysis aligns with previous research on the CDoH and healthcare-industry relationships, this is the first article, to our knowledge, that applies an ethics analysis to a fictionalized case of psychedelic industry sponsorship of a research and treatment program that has an explicitly public mission.

Some scholars advocate for healthcare professional-industry relationships as necessary to advance knowledge, maintain innovation and progress and benefit society (Jones and McCullough, 2002; White, Vaccaro and Zdeblick, 2007). There has been considerable scholarship defending the pragmatic importance of these relationships, with the caveat that conflicts of interest are not inherently problematic per se but rather the ethical issues relate to how they are managed (Jones and McCullough, 2002). Indeed, some healthcare-industry relationships may be valuable, and it is not always clear when those relationships are not in the interest of the public (Rosenbaum, 2015). However, critics of these arguments point to the substantial empirical evidence on motivated reasoning—a cognitive bias which leads to justifications based on what we wish to be true as opposed to what scientific evidence suggests—which includes studies indicating a strong influence of corporate activities on clinicians’ and scientists’ behavior (Moore and Loewenstein, 2004; Goldberg, 2016; Bruton and Sacco, 2018). Critics also point to well-trodden management strategies, such as transparency and disclosure, as thought to be sufficient ethically. Indeed, disclosure and transparency are important for audiences to assess the independence of the sponsoring group and evaluate the objectivity of the data. While disclosure and transparency-focused efforts are a good start, transparency is necessary yet insufficient for conflict of interest disclosures. Disclosures tend to be incomplete, inconsistent and challenging to assess (Grundy, Dunn and Bero, 2020), require minimal management, and do not modify the relationship. Furthermore, the empirical literature has repeatedly demonstrated the ‘perverse’ effects of conflict of interest disclosure, including leading the person disclosing to provide more biased advice—advice that has been warranted because the audience has been ‘warned’ of the conflicts—and that the audience may inadvertently trust the person disclosing more because they were transparent (Loewenstein, Cain and Sah, 2011; Loewenstein, Sah and Cain, 2012).

While our analysis suggests high to extremely high risks of moral jeopardy with accepting money from the for-profit psychedelics sector, the Adams framework provides a risk-based assessment within a continuum that centers mission and values, as opposed to a complete ‘sequestration’ from all industries (Schafer, 2004). As part of our process, the group did identify industries that were completely off limits such as weapons, predatory lending corporations, and the alcohol and tobacco industries, among others, citing known harms to population health. The group also considered the extent to which accepting funds from any for-profit sector represents a clash of purpose, insofar as the purpose of capitalism is to maximize profit, whereas the purpose of a health sciences center and the programs it houses is ultimately to support individual and community health. The relationships between accumulation of corporate profit, massive social inequity and poor health outcomes are well established and the profit motive in general was felt by the group to be incompatible with public health. However, the group also felt that there are salient differences between industries based on the specific harms associated with their products and practices, as described above. For example, the clash of purpose is much weaker if a company (with established safe practices) produces what is likely to be considered a benign product, such as jewelry produced ethically from local resources, than if the company produces a product, such as weapons, that is clearly harmful for human health and well-being.

Limitations

Starting from a fictionalized case example, our analysis is based on what this team would do if faced with the question of for-profit psychedelic sector sponsorship, which may differ from what they would actually do in a real-world setting. This is similar to the hypothetical bias described in the research design literature (Haghani et al., 2021). Other groups may weigh the Adams’ domains differently. However, there are numerous psychedelic research centers arising throughout North America and Europe, so the dilemma we describe in the article and the case analyzed here is not entirely hypothetical.

Conclusions

Psychedelic therapies may offer much needed benefits for people living with mental illness and SUDs, and it is unsurprising that the for-profit industry would be keen to capitalize on these developments through familiar corporate mechanisms such as financial sponsorship of people and programs of research. As psychedelic research continues to develop in an environment of limited public funds for research and precarious academic labor, there is an urgent need for independent research to produce trustworthy evidence. This is so we can understand the safety and efficacy of psychedelic therapies in a variety of clinical populations (Moynihan et al., 2019; Hall, 2021).

Many of the concerns we have outlined about healthcare relationships with industry are not new, but they remain relevant to emerging for-profit industries such as psychedelics. The fact that we are still having the conversation about the degree of permissibility of financial entanglements with industry—despite the evidence of population health hazards—suggests that there is still much work to do. Our current legal and policy responses need to go beyond the individual and institution and address the issue through structural and systemic responses in policy and law (Marks, 2019). By no means do we endorse the current status quo with respect to the pressure to rely on private funding sources for research. We join others in calls to increase public investment in research in order to minimize financial dependence on corporate interests (Moynihan et al., 2019; Muthukumaraswamy, Forsyth and Sumner, 2022). While PERIL is a useful ethical decision-making framework individuals and organizations can apply to decide whether to accept funding support from industry sources such as the for-profit psychedelic sector, it does little to mitigate the population health ethics issues generated by capitalism and the broader commercial determinants of health.