Psychedelic Clinical Trials: Insights from PSC 2025

The landscape of psychedelic medicine is experiencing a transformation as profound as the therapies themselves, moving from early-stage enthusiasm to the rigorous demands of clinical science.
At the Psychedelic Science 2025 conference in Denver, the prevailing mood in the Business and Clinical Trial tracks reflected this evolution: curiosity and optimism remain high, but the conversation has decisively shifted toward methodological rigor and regulatory readiness, especially considering recent FDA decisions on psychedelic compounds.
Throughout sessions and informal discussions, a consensus crystallized: the future of psychedelic therapies will depend not on their novelty, but on their ability to withstand the same scientific scrutiny as any other therapeutic modality. One speaker put it concisely: “Passion and exceptionalism alone are not sufficient.”
Blinding and Bias: Operationalizing Scientific Integrity
Psychedelic compounds present a unique challenge to traditional blinding paradigms. The rapid and unmistakable onset of subjective effects renders simple capsule-matching inadequate. Even with meticulously designed placebos, both participant behaviors and investigator expectations can compromise the blind, introducing bias that threatens the validity of results.
Signant Health’s teleconference-based Central Rating solution addresses this by structurally separating treatment administration from rating via remote assessment. This insulation not only preserves the integrity of the blind but also bolsters the confidence of regulators in the resulting data.
Our central rating services have been deployed in positive complex trials worldwide, providing a proven framework for maintaining scientific rigor in the face of operational complexity. Several presentations at the conference noted that while effects were initially large after active dose, over weeks/months they are difficult to sustain, which may be due in part to rating bias; our central raters can be blinded to visit to minimize that concern.
Rater and Rating Quality: Eliminating Variability at the Source
Outcome measurement in psychedelic trials is acutely sensitive to rater variability, especially given the profound and sometimes unpredictable alterations in consciousness induced by these compounds. Reliability in scoring is essential for scientific validity.
Our expertise in comprehensive rater training, qualification, and ongoing calibration—spanning both site-based and central raters—ensures that every assessment is robust and reproducible.
Augmenting this, Signant Health’s central review of primary endpoint audio/video administration by clinical experts adds an additional layer of quality control for site-administered scales.
For psychedelic trials, our blinded data analytics platform, PureSignal Analytics, rapidly detects anomalous data patterns, reducing noise and enhancing reliability across sites via active intervention. Our data-driven site selection services further ensure that only the highest-performing sites contribute to your trial, maximizing both efficiency and data quality.
Placebo Response: Navigating a Persistent Challenge
Multiple presentations at the conference described cases where subjects on placebo reported they thought they received active medication. Unchecked, placebo effects can obscure true treatment signals and jeopardize trial outcomes.
Signant Health’s multi-modal Placebo Response mitigation strategies are specifically tailored for psychedelic studies, equipping both site staff and participants to minimize unconscious reinforcement cues and adhere closely to protocol intent. The result is a cleaner signal, more statistically powerful studies, and a substantial reduction in the risk of costly post-hoc adjustments.
One of the most critical, yet often overlooked, determinants of trial success is the quality of subject selection. In psychedelic research, where subjective experience is both the intervention and the endpoint, enrolling participants who are reliable is paramount.
Our proprietary tandem ratings method employs a multidimensional assessment to identify subjects who are not only eligible according to protocol guidelines but also demonstrate high reliability and minimal susceptibility to placebo response.
Conclusion: Where Substance Meets Standards
The message from Psychedelic Science 2025 is unequivocal: innovation must be matched by scientific discipline. Regulatory agencies are demanding not just novelty, but robust evidence generated through impeccable trial design, execution, and data integrity.
Signant Health stands at the forefront of this new era, supporting every phase of psychedelic clinical trials with our scientifically grounded, globally scalable infrastructure.
About the authors Rachel Berman, PhD., brings two decades of neuropsychology experience to Signant Health, including clinical science work in differential diagnostic services and geriatrics. Specializing in psychiatric and neurological disorders like schizophrenia, bipolar disorder, and behavioral/neuropsychiatric symptoms in dementia, Rachel supports sponsors and CROs running trials in these and other CNS indications. She also lends her expertise to Signant’s original research projects and business development team, ensuring that the highest caliber scientific solutions are offered to meet each unique clinical needs.
Gary Sachs, MD, is a Therapeutic Area Leader in bipolar disease and mood disorders and Clinical Vice President at Signant Health. He is a recognized expert in clinical trial methodologies. He founded the Bipolar Clinic at Massachusetts General Hospital and is an Associate Professor of Psychiatry at Harvard Medical School. With over 200 publications, Dr. Sachs also serves on the Scientific Advisory Boards of the National Alliance on Mental Illness and the Depression and Bipolar Support Alliance.