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Groundbreaking Guidelines Improve Psychedelic Clinical Trials by Standardizing ‘Set and Setting’
Montreal – In a move poised to revolutionize psychedelic research, a panel of international experts has forged the first consensus-based framework for reporting “set and setting” variables within psychedelic clinical trials. these guidelines, which were published in Nature Medicine on June 3, 2025, establish a standardized protocol that comprehensively accounts for both the mental state of the user and the surroundings in which the psychedelic experience unfolds.
the new Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines aim to introduce much-needed rigor and consistency into a field where contextual factors can dramatically influence outcomes. This framework offers a foundation for future studies and regulatory decisions.
Why Context Matters in Psychedelic Experiences
It’s widely acknowledged that the “set and setting”-a person’s mindset and environment-profoundly shapes the psychedelic experience. dr. Chloé pronovost-Morgan, Psychiatry Resident at McGill University, emphasized that the same drug dose can elicit vastly different reactions based on context, ranging from severe anxiety to profound mystical experiences.
A recent systematic review revealed that the majority of psychedelic trials provide sparse details about the context, which makes it difficult to accurately interpret, replicate, and apply findings.Imagine taking psilocybin in a quiet countryside room versus inside a noisy brain scanner. The setting matters.
The ReSPCT Framework: A Detailed Look
The ReSPCT framework encompasses 30 variables, categorized into four essential sections:
- Physical and Sensory Environment: Details about the study setting, room design, sensory modulation tools (eye shades, noise-canceling headphones), and the presence of decorations like artwork or religious items.
- Dosing Session Procedure: Includes who was present, use of music, verbal and physical interactions, consent protocols, participant autonomy, dosing regimen details, and any disturbances.
- Therapeutic Framework and Protocol: Covers topics such as patient history review, intention setting, addressing concerns, psychoeducation, and the credentials/training of staff, including cultural competence.
- Participants’ Subjective Experience: Captures their perceptions of the environment, therapeutic rapport, sense of comfort, and feelings of safety.
Did You Know? The presence of religious iconography can substantially influence how participants interpret their psychedelic experiences.
Expert Insights on the New Guidelines
dr. Matthew W. johnson, a researcher at Johns Hopkins University School of Medicine, noted that context is often underreported, even in studies he’s participated in.He stressed the importance of including seemingly minor details, such as the presence of religious items, which some researchers avoid due to concerns about perceived bias.
According to Johnson, trial publications often underreport preparation time. He advised that the actual preparation time is often longer than what is reported to the public.
Impact on Future Research and Regulatory Approval
The panel advocates for the inclusion of the 30 ReSPCT variables in publications to facilitate comparisons across trials. This standardized approach could illuminate which contextual factors most significantly influence clinical results. These guidelines will help researchers, clinicians, and regulatory bodies gain a better understanding of what these therapies entail as a whole.
Pronovost-Morgan stated that this clarity could help move beyond tradition and intuition toward evidence-based contextual care.
The FDA recently rejected MDMA-assisted therapy for PTSD, citing inconsistent reporting across trials. Paul E. Holtzheimer, MD, director of the VA’s National Posttraumatic Stress Disorder Brain Bank, described the therapy element as a “black box.”
Co-senior author Dr. Leor Roseman said the new guidelines would help in replicating results and understanding the true therapeutic potential of psychedelics. the panel predicts that this should increase the chances of regulatory approval for psychedelics.
Contextual Influences Beyond Psychedelics
Dr. Kyle Greenway from McGill University emphasized that contextual influences extend beyond psychedelic drugs and consciousness-altering effects. Preclinical and clinical evidence suggests that contextual influences can be significant for a wide variety of drugs, from antidepressants and benzodiazepines to alcohol and opiates.
Psychedelic drugs may provide the most striking examples of drug
