Table 1 Provisional guidelines for clinical research trials

Risks associated with screening (e.g., overlooking comorbidities, selecting a psychedelic incompatible with participant’s existing medications)

Careful interdisciplinary screening with a psychiatrist/MD, pharmacist, and psychologist. Develop guidelines for screening participants in psychedelic-assisted therapy trials.

Informed consent is challenging to obtain, especially from those without past experiences with psychedelics

Accurately convey current research evidence, alternative treatment options, and the wide range of possible experiences and outcomes, as well as the risks of adverse events. Co-develop information packages and consent materials with people who have received PAT.

Risk for adverse effects

Thorough informed consent process; exclude participants with personal or familial history of bipolar or psychotic disorders; ensure sufficient psychological preparation before treatment; ensure appropriate medical equipment and personnel, including therapeutic supports before, after, and during drug administration; rigorous monitoring and reporting of adverse events. Practitioners should have appropriate training and supervision in psychedelic-assisted therapy as well as eating disorder treatment; development and implementation of stringent safety standards and protocols.

Developmental concerns for younger age groups

Extreme caution for younger age groups until more research demonstrates absence of harm.

Studies with no control group, small sample sizes, and short study duration have limited internal validity.

Larger, double-blinded, randomized control trials of psychedelic-assisted eating disorder treatment; include control groups, achieve adequate power, and have longer term follow-up (> 12 months). Adaptive trial designs represent a flexible alternative. Team science/multi-center collaborations can mitigate costs (van Elk and Fried, 2023). If further open-label studies are conducted, researchers should interpret data cautiously and clearly explain design limitations.

Placebo effect secondary to positive expectancy.

‘Unblinding’ (of participants and researchers) due to obvious psychoactive effects of psychedelics.

Include measures of expectancy and social desirability, and control for these variables. Manage participant expectations prior to study commencement (e.g., adding explicit information in consent forms about the uncertainty of psychedelics’ positive effects). Blinding can be enhanced by using ‘active’ placebos (e.g., psychostimulant, diphenhydramine, low dose psychedelics, and/or antidepressants). Recruit psychedelic-naïve participants because they will have less awareness of the psychedelic effect, and hence, will be more likely to be ‘blinded’ to group assignment. Assess and report on success of blinding of both participants and researchers.

Uncertain economic viability

Further research on cost effectiveness, with attention to equity and accessibility; safeguards to prevent financial conflicts of interest.

Racial inequity and extractivism

Greater inclusion of BIPOC in psychedelic research, not only as participants, but community partners to guide research and decision-making.

Insufficient focus on psychotherapy interventions used in PAT

Adaptations of existing evidence-based eating disorder treatment approaches; thorough reporting and transparency in therapy protocols; incorporating fidelity assessments; examining impact of specific interventions, subjective psychedelic experiences, and general factors of psychotherapy.