The challenges ahead for psychedelic ‘medicine’

This paper (2022) discusses a number of challenges inherent to psychedelic medicine including the challenges related to the design of individual research studies such as blinding, expectancy, the use of therapy and sources of bias. The broader researcher environment and issues related to evidence, funding and the current scheduling of psychedelics are just some of the other topics discussed.

Abstract

“With the extensive public, commercial and scientific interest from what has been widely termed the psychedelic renaissance, it is important that the scientific practices and results obtained from its implementation into medicine are put under a critical microscope. While there are numerous works on the potential benefits and applications of psychedelics as medicines, relatively little has been written about the challenges this field will face when incorporated into modern medical practice. Indeed, as a new or at least revived area of investigation, psychedelic medicine has a particular set of challenges that need to be addressed. In this viewpoint, we identify a number of these challenges. First, challenges related to the design of individual research studies are discussed, particularly focusing on current practices surrounding blinding, expectancy, the use of therapy and sources of bias. Second, the broader context of the research environment is considered, including how medical science typically establishes evidence, funding bodies and the impact of psychedelics being scheduled at odds with their risk profile. Finally, we describe challenges relating to the implementation of psychedelic therapies into modern medicine, considering the social and economic context. Alongside, we provide suggestions for what could be included into current research protocols to mitigate these challenges.”

Authors: Suresh Muthukumaraswamy, Anna Forsyth & Rachael L. Sumner

Notes

Psychedelics are poised to be a game-changer in how we view and treat mental health disorders. These psychoactive substances have a relationship with science and society like no other pharmacological agents. Prior to becoming Schedule I substances following the introduction of the Controlled Substance Act in 1970, researchers were working with these substances. While research from this era pointed toward the therapeutic potential of psychedelics, it was largely marred with methodological flaws and practices that would be considered unethical by today’s standards. If psychedelics are going to become viable therapy options, researchers must now contend with the fallout from this era and must overcome new hurdles that continue to present themselves in this modern age of psychedelic research.

The present paper outlines some of the issues faced by modern psychedelic researchers and provides some thoughts on how the challenges they face can be mitigated. The authors outline issues that are inherent to clinical research as well as the broader research environment, discussing issues such as funding, the current scheduling of psychedelics and the need to be transparent.

Factors related to individual research studies:

• Blinding – Used in clinical trials to limit the occurrence of conscious and unconscious bias although in clinical trials with psychedelics it has proven both difficult to achieve and maintain. Unblinding can affect results due to expectancy effects and therefore, trials must be designed in such a way that participants’ beliefs about whether they are in the treatment arm of the trial are approximately matched across groups.
• Therapeutic alliance – The psychotherapy aspect of many trials with psychedelics has the ability to affect treatment outcomes and may enhance the placebo response. Moreover, a therapist may become aware if a patient has been assigned to the treatment group based on their reaction and could potentially deliver different therapeutic processes based on this.
• Expectancy – Many patients in these trials can have preconceived notions regarding their response to treatment and current positive media coverage of psychedelics may be inflating this issue. Whether or not expectancy effects could be held constant remains open to debate. Furthermore, it is unclear whether there are any drugs that would serve as convincing placebos.
• Statistical Power – Many clinical trials with psychedelics are conducted in small samples which reduces the generalizability of results. Trials with large sample sizes are required and may be possible through multisite studies.

Factors related to the broader research context:

• Real-world evidence should be considered when proving the therapeutic effects of interventions, particularly when considering the aforementioned issues in clinical trials. If used, an adequate set of criteria for and against these therapies would need to be developed.
• Full transparency is needed. One step researchers could take is the publication of full clinical trial protocols in peer-reviewed academic journals.
• Public funding is needed as such trials tend to face a more rigorous peer-review process and scientific assessment when compared to philanthropic endeavours.
• The current scheduling of psychedelics stands at odds with their safety profile and as a result, potential therapeutic applications will continue to impact and create biases in their evidence base. Furthermore, research will remain costly and restricted to the highly controlled research environments unless psychedelics are rescheduled.

Designing research for future use in standard medical practice:

• Psychedelic therapy research design should include techniques to manage the risks relating to the changes in consciousness resulting from the psychedelic experience. Some techniques include multiple practitioners, transparent practices and videotaping sessions.
• Unregulated self-treatment may become more common as the general public increasingly view this class of drugs as viable medicines and ultimately increase the prevalence of adverse events in light of challenging experiences.
• Current models of psychedelic therapy are extremely resource-intensive, creating issues regarding accessibility and entrenching healthcare inequality. There is a need for research into lower-cost alternatives to the current resource-heavy model.
• Incorporating traditional practices into modern research into psychedelics may be of significant therapeutic value and help to maintain the cultural heritage of the indigenous groups who have stewarded much of psychedelic medicine.

Summary of The challenges ahead for psychedelic ‘medicine’