Assuming the efficacy of psychedelics and related compounds is demonstrated for the treatment of mental disorders, the actual benefit derived from implementing these medications in clinical practice is going to depend on a variety of issues, said Paul Appelbaum, the Elizabeth K. Dollard Professor of Psychiatry, Medicine, and Law at the Vagelos College of Physicians and Surgeons at Columbia University. Among these issues is ensuring access and equitable distribution of benefits, especially to people of color and those with limited means, said Appelbaum. Psychedelic treatment may also increase the vulnerability of patients to abuse, he said. There are also questions about how the highly restrictive legal status of these Schedule I
drugs,1 which has hampered research into their clinical effects, may affect the clinical implementation or how the laws may change to enable their use as therapies, said Appelbaum. Other considerations include the potential for abuse and misuse of these medications, off-label prescribing, and commercialization issues.
FRAMEWORKS FOR ACCESSIBLE AND EQUITABLE IMPLEMENTATION
Designing a framework for implementation of research and clinical care that reflects principles of health justice is critical in all areas of health care, but especially with respect to psychedelics, according to Melissa A. Simon, the George H. Gardner Professor of Clinical Gynecology at the Northwestern University Feinberg School of Medicine and the founder and director of both the Center for Health Equity Transformation and the Chicago Cancer Health Equity Collaborative. This framework must address inequality, equity, and justice, she said. Inequality exists when policies or practices favor certain people or groups while actively disadvantaging others, said Simon. Addressing equity requires recognizing that existing policies and practices are inequitable while at the same time providing people with different types of supports that allow them to access their goals despite disadvantages, she added. Finally, Simon said ensuring health justice requires a diverse group of people to evaluate why policies, practices, treatments, and research designs are inequitable.
Acknowledging history is essential in building a health equity and health justice framework, said Simon. “We know that our country has a deep and long history of slavery, racism, and discrimination,” she said, including histories of egregious experimentation. Even today, systemic racism limits access of some minoritized and marginalized populations to novel health treatments including psychedelics as well as to clinical trials, said Simon. Not only people of color, but other minoritized populations, such as LGBTQIA+ people, experience significant health disparities compared with heterosexual and cisgender people, added Caroline Dorsen, associate dean of clinical partnerships at the Rutgers University School of Nursing. She added that many of the health care disparities that are especially prominent among LGBTQIA+ people are in the same areas that psychedelics hold promise to address—depression, anxiety, suicidality, and substance
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1 According to the U.S. Drug Enforcement Administration (DEA), “Schedule I drugs, substances, or chemicals are defined as drugs with a high potential for abuse, no currently accepted medical use in treatment in the United States, a lack of accepted safety for use under medical supervision.” For more information, see https://www.dea.gov/drug-information/drug-scheduling (accessed August 4, 2022).
use disorders. Barriers to accessing psychedelics research studies and care also exist for people with physical disabilities, blindness, hearing impairment, or autism, said Dominic Sisti, assistant professor of medical ethics and health policy at the University of Pennsylvania. He added that people with disabilities also carry a much higher burden of certain mental illnesses that these agents might be able to treat. “We have an ethical obligation to prioritize individuals with disabilities in this research and in practice, but this has not really happened,” he said.
Simon noted that the entire research pipeline is fraught with structural racism. Although, Black and Latinx populations represented 13.4 percent and 18.1 percent of the U.S. population in the 2020 census, these populations participate in clinical trials at far lower rates and comprise far lower percentages of U.S. physicians and researchers compared to White people, said Simon. If a study does not have diverse participants, the generalizability of the results may not apply to much of the population, she said. Simon’s research team at the Center for Health Equity Transformation has worked with the Health for All Project2 to better understand how to improve clinical trial participation among minoritized populations. Trust is key, she said. “We have got to work really hard to get back that trust that we severed with our egregious history,” said Simon. Dorsen noted, however, that there are few data regarding the participation of LGBTQIA+ people in clinical studies because sexual orientation and gender identity data may not be collected from clinical trial participants.
Diversity among researchers and clinicians is also critical to the impact on—and how connected the research studies are to—minoritized populations, she said. Similarly, “journals, editorial teams, reviewers, and publication opportunities are all fraught with bias,” said Simon. “If we are trying to get clinical trials published in key journals, having appropriate editors and reviewers and journal expectations of diverse participation in trials is critical,” she added.
Inequities also exist along the entire health care delivery pipeline, said Simon. In developing a framework for accessible and equitable implementation of psychedelic therapy, implementation science is critical, she said. This discipline aims to bridge the science–practice gap using a variety of approaches, including process models, determinant frameworks, and evaluation, she said. In combination with disparities research, implementation science can offer methods and test strategies intended to reduce disparities, said Simon.
Some of the critical access dimensions to consider are risk factor management, quality and consistency of care, training of a diverse and culturally
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2 To learn more about the Health for All Project, see https://healthforallproject.org/about (accessed June 4, 2022).
humble workforce, financial issues such as insurance and reimbursement, social and economic determinants of health, health literacy, stigma, and trust, she said. Community health workers and navigators are crucial to building a bridge of trust to the health care system, said Simon. “What is essential to this system working well is care delivery that prioritizes the needs of patients,” she said.
BUILDING TRUST WITH MARGINALIZED COMMUNITIES
Charma D. Dudley, vice president of the National Alliance on Mental Illness (NAMI) board of directors and associate director of behavioral health services at Beacon Health Options in Pittsburgh, reinforced the importance of trust. She noted that as a result of the history of Black and Brown people being used for experimental research, and the fact that people of color experience substantial barriers to treatment, “experimental research does not sit well [with them].” When presented the opportunity to receive psychedelics for the treatment of depression, posttraumatic stress disorder (PTSD), or other mental health conditions, Dudley said they may have important questions that need to be answered such as “Is this going to make me crazy?” or “Am I going to lose control?” or “How is this going to help me?”
Medical mistrust may also be a barrier to access in the LGBTQIA+ community, where psychedelics have been used as tools of oppression and possibly as “conversion therapies,” added Dorsen.
People do not like to be vulnerable, particularly when they come from a group of people who have experienced oppression, discrimination, and racism on a daily basis, said Dudley. “We need to address the lack of trust in these communities; have open, honest conversations with people regarding psychedelic drugs; and promote awareness,” she said.
She added that the Black community is “all about it takes a village.” When recommending a course of psychedelic therapy, she suggested allowing them to bring a relative or friend to one of the preparatory sessions, and exposing them to stories of Black and Brown people who have experienced psychedelic therapy would also be helpful, she said. People also want to know that there are people who look like them among the principal investigators and mental health professionals, said Dudley.
Building trust also means educating the community by having researchers go into communities where marginalized people live and talking to ministers, community leaders, activists, and other trusted community members, said Dudley. Simon agreed, noting that every community has different gatekeepers and arbiters of trust. She added that because Native communities have a long history of the use of psychedelics, acknowledging and valuing that history and then linking it to the treatment of mental health conditions is critical.
Intentionally creating inclusive and affirming psychedelic-assisted care for marginalized communities with health disparities, such as LGBTQIA+ people, may be needed, suggested Dorsen. For example, she asked whether processes and protocols exist that speak specifically to the unique culture and health care needs of LGBTQIA+ people. Some protocols call for male/female dyads as therapists, she said, but people who are gender diverse may feel that a binary male/female dyad may not provide the comfort level they need to support a positive therapeutic outcome, she said.
ENSURING SAFE AND ETHICAL RESEARCH AND CARE PRACTICES
As market and social forces quickly propel psychedelics from research to clinical practice, Sisti said a strong ethical scaffold needs to be in place for what is essentially a new medical subspecialty. This would include a comprehensive code of ethics and professionalism, a description of clinical and ethical core competencies, and clear credentialing standards and licensing requirements. Institutional structures are also needed to ensure accountability and sanctions, he said.
Training and credentialing will be required across professions, noted Appelbaum. Even mental health professionals rarely receive the appropriate training, he said. Dorsen noted that the nursing field does not currently have content about psychedelics embedded into its curriculum, although nurses have expertise and experience working with patients in vulnerable moments. She added that some medical schools have initiated collaborative psychedelic psychiatry programs and expressed the hope that nursing schools and schools for other health professions will follow suit. Nurses may have a particularly important role to play in the scalability and delivery of psychedelic therapy because nurses try to “be present for people in illness and in health and see them through vulnerable moments in life,” said Dorsen. She suggested there could be roles for many different types of nurses in the psychedelics space, including registered nurses and mental health nurse practitioners who are trained to do psychotherapy as well as doctorally prepared nurses with expertise in quality improvement who can ensure accurate translation of knowledge from clinical trials into the more complicated real-world space.
Steven Levine added that challenges to providing mental health care services are particularly significant in historically underserved communities. Even where professionals are available to deliver needed services, not all of them are reimbursed by Medicare or Medicaid. He said there are active bills looking to potentially expand the reimbursable mental health workforce. There may also be opportunities to expand the mental health workforce through programs like certified peer professionals, although
because by definition they would not be trained to deliver psychotherapy or advanced mental health services, the role they would play would need to be defined, said Levine.
Reinforcing what has been previously discussed, Sisti noted that the ethical perils of psychedelic research have been seen throughout its history with egregious examples of unethical research. While psychedelic investigators today must follow a careful regulatory pathway, federal laws, and institutional rules, problems still exist, and there is no consensus about basic ethical questions related to the psychedelic clinical encounter, such as whether it is ever acceptable for researchers or clinicians to touch patients, he said. While some researchers address this question in informed consent and preparatory sessions and try to mitigate the risk through the use of video recording, Sisti said these measures do not always work, resulting in disturbing cases of sexual and psychological abuse in both research and “quasi-underground clinical settings.”
He added that certain kinds of touch may be effective and appropriate in therapeutic settings, although even well-intentioned touch may trigger or worsen trauma. To establish broad public trust in this mode of therapy and enable it to be integrated into the health care system, he advocated for harmonizing ethical standards related to touch with the ethical rules for other behavioral health care professionals. As part of the robust U.S. Food and Drug Administration (FDA) risk mitigation program, Sisti suggested establishing safety guidelines and enhanced consent procedures to allow for touch in very specific circumstances. He also suggested screening procedures to “weed out individuals who are ill equipped for these very sensitive patient encounters,” for example, individuals drawn to the power of psychedelics and entactogens and the substances’ ability to induce suggestibility in an already vulnerable group of individuals. Finally, Sisti said research is needed to identify characteristics of effective therapists in order to filter out the bad apples and provide data for developing evidence-based curricula.
Although patient consent is critical to ensuring safety, Sisti noted several complications. “The consent process itself requires the disclosure of what is essentially ineffable knowledge about the experience that the patient is about to undergo,” he said. “That, in and of itself, creates problems in terms of what is the scope of disclosure, how much information you ought to disclose, and what types of information.”
Sisti said most researchers use the preparatory session as part of the consent process. They might ask, for example, if the patient would like to be touched if they are struggling with difficult thoughts during the treatment session. However, Sisti noted that sometimes a person will endorse using touch during the preparatory session, yet change their mind during the treatment sessions. “It really boils down to the individual clinician in
the moment, drawing on the experience, competency, and wisdom to figure out what is the best choice in that case,” he said.
Sisti advocated for an enhanced consent process that helps patients understand what they are about to experience and how it aligns with their values. Through that process, he said, clinicians and researchers may better understand what is appropriate and inappropriate in various situations. Another idea, he said, is to allow family members or other loved ones to be in the room with the patient. Such supportive players would need their own preparation to understand their roles and commit to not being disruptive, said Sisti. Appelbaum added that family members are not always neutral in a person’s life, and having them in the room would need to be considered carefully on a case-by-case basis.
Commercialization and Lessons from Ketamine Treatment
Issues around patient access to psychedelics and entactogens were mentioned frequently throughout the workshop. For example, in Chapter 2, in describing her experience receiving methylenedioxymethamphetamine (MDMA) for posttraumatic stress disorder (PTSD), Lori Tipton endorsed the idea of community models of care as a means of reducing barriers that exclude many people in need, especially the historically marginalized. In her remarks, she acknowledged the privilege she has as someone who was able to receive this treatment. She expressed concern about the accessibility of these drugs and therapies, noting that where she lives in New Orleans, many people lack access to basic health care and mental health care. “I have complete faith in the potential of this drug, but I have concerns regarding who will be able to access it in the future,” she said.
There are lessons to be learned about the implementation of psychedelic therapy from the off-label and therapeutic use of the anesthetic ketamine and esketamine, which are approved for treating treatment-resistant depression and depression with suicidality, said Levine. While not a psychedelic, ketamine also has psychoactive properties, Levine said. He treated or supervised more than 6,000 patients receiving intravenous ketamine (Levine, 2021). Because this was an off-label use of the drug, it was not reimbursable by payers and therefore unaffordable to many, he said. “There is a paradox that the medicine is cheap, but the delivery is resource intensive and therefore expensive,” said Levine.
In 2019, FDA approved esketamine for treatment-resistant depression, with accompanying risk evaluation and mitigation strategy (REMS) and regulated safety standards, which required psychiatrists to be certified to provide this treatment, said Levine. However, he noted that there was no
CPT code3 and no requirement or means to bill for psychological support, nor was there evidence showing the need for psychological support to ensure safe and efficacious treatment with esketamine. Frustrated psychiatrists quickly reverted to using unregulated racemic ketamine instead, he said.
Looking ahead to upcoming psychedelic therapies should they be approved, Levine said that to achieve broad, safe, and equitable patient access, there will need to be a coding and reimbursement structure in place that is understood by providers and payers and financially viable for them. “In other words, there is a risk that we develop paradigm-shifting new treatments that never get to the patients who may benefit from them and a possible divergence to less regulated routes to access with the accompanying risks or harms,” said Levine.
The commercialization of unregulated ketamine led to the proliferation of clinics around the country, added Appelbaum. Some of these clinics are also poised to deliver psychedelic therapy, once it is approved, and may do so with no mental health services or psychotherapeutic component, he said. Levine noted that the approval of esketamine offered some hope of reducing the unregulated use of ketamine. However, lower uptake of esketamine fueled the growth of these less regulated and potentially less safe clinics providing ketamine.
While FDA does not regulate off-label use, including practitioners advertising to the public about providing treatment with psychedelics for specific psychiatric disorders, Javier Muñiz noted that there is an Office of Scientific Investigation within the administration with authority to investigate practices that may fall outside a practitioner’s purview. In addition, because these are controlled Schedule I substances, DEA may take action, he said.
NAVIGATING THE LEGAL COMPLEXITY OF MEDICALIZING SCHEDULE I SUBSTANCES
Anthony Coulson, president and owner of NTH Consulting, Inc., and a retired agent of DEA, provided insight into the complicated path to clinical implementation of psychedelics because of their designation as Schedule I substances. In terms of enforcement of laws pertaining to drug use, Coulson said that DEA is essentially a “prohibitionist organization,” driven by agents with no training in the field of medicine or scientific research. On the regulatory side, however, they have done a good job of managing the supply of psychedelics in the United States, he said.
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3 A Current Procedural Terminology (CPT) code is a medical code established by the American Medical Association to provide uniform language for insurers and health care providers to use when reporting provision of medical services and procedures. To learn more, see https://www.ama-assn.org/practice-management/cpt/cpt-overview-and-code-approval (accessed June 5, 2022).
Coulson said that DEA “defaults to old definitions,” for example, using what he considers to be the pejorative word “hallucinogen” rather than psychedelics. The term “hallucinogen” itself is a barrier to research, he said. Yet, he said that while DEA regulations may make it difficult to initiate psychedelics research projects, once a project is given the green light to begin, DEA can be helpful in getting the research done.
Rescheduling a Schedule I agent to a less restrictive designation is within the purview of DEA, yet Coulson said they have no experience in rescheduling psychedelics. They tend to follow the lead of FDA when the research community has persuaded FDA that a drug has a medical benefit. FDA approval triggers DEA consideration of the scheduling designation, he said. However, for DEA, the crux of their decision rests on the drug’s abuse potential, said Coulson. Moreover, DEA has the final authority to reschedule a drug unless Congress legislates a change.
Lessons from the Religious and Sacramental Use of Psychedelics
Coulson said that DEA takes a benign enforcement policy to the religious or sacramental use of psychedelics. It is common knowledge that psychedelics are used in these settings, added Dorsen, yet the regulatory and legal issues surrounding these agents make it hard for researchers to learn from the experiences of this community. In particular, these communities could provide potentially valuable lessons related to efficacy, delivery, and access, she said. “People in that community are serious people who are serious about health and healing,” said Dorsen. They prioritize emotional and physical safety and have created a system to hold each other accountable as they take these substances to deal with trauma, depression, anxiety, PTSD, and substance abuse, she said. To achieve this, they have incorporated many of the same structures and processes used in clinical trials, such as trained facilitators, music, intention-setting preparatory sessions, and debriefing sessions to make sense of the experience.
Dorsen suggested that these communities could also provide valuable lessons around the practice of delivering psychedelic therapy in group and community settings. This approach could not only increase access and decrease financial burden but may also provide other benefits in terms of reducing the social isolation and lack of connection that may underlie depression, anxiety, and substance abuse. “The group environment, just like group therapy, creates the opportunity for interrelational healing that individual work does not,” said Dorsen. She further suggested that as people in these groups begin to see their health in the context of a larger community or culture, there may also be larger benefits to the community.
Dorsen noted that many questions will need to be resolved regarding delivery of psychedelic therapy in group settings, including who is most
likely to benefit from a group setting; how should the groups be constituted, for example, would people be grouped on the basis of their life experiences or diagnoses? What sort of preparation and integration would be needed? Would dosing be different because of the interaction of group energy? She suggested that there may also be other unintended benefits from groups, such as increased empathy and decreased bias.
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