Psychopharmacology
April 1, 2022
Jacob S. Aday, Boris D. Heifets, Steven D. Pratscher et al.
214 citations
Psychedelic research faces unique methodological challenges beyond those typical of psychotherapy and pharmacology trials. The pronounced subjective effects of high-dose psychedelics make it difficult to mask participants to their treatment condition. Positive media coverage inflates participants' expectations for benefit, and unmasking combined with expectations can produce large placebo and nocebo effects. Recommendations to improve masking and reduce expectancy bias include careful study development, participant recruitment and selection, incomplete disclosure of study design, choice of active placebo, and measurement of expectations and masking efficacy. Incorporating these design elements aims to reduce bias and improve the ability to discern treatment-specific effects.
JAMA Psychiatry
June 1, 2023
Jacob S. Aday, Robin L. Carhart-Harris, Joshua D. Woolley
48 citations
The abstract discusses emerging challenges for psychedelic therapy, highlighting obstacles such as regulatory hurdles, accessibility issues, equity concerns, and the need for practitioner training. It underscores difficulties in integrating psychedelic treatments into mainstream healthcare, including governance, legal frameworks, and developing accessible and equitable treatment models. The text suggests that responsible integration requires addressing these barriers to ensure safe and effective mental health care.
Front Psychiatry
June 10, 2024
Leehe Peled-Avron, Jacob S. Aday, Amilia Lydia Kalafateli et al.
2 citations
Psychedelic compounds produce profound alterations in consciousness and perception, and emerging evidence suggests they may be effective treatments for several mental health and medical conditions. This editorial introduces a collection of articles that explore the psychological and neural mechanisms underlying these effects, including how psychedelics modulate brain networks, promote neuroplasticity, and facilitate therapeutic change. The authors argue that understanding these mechanisms is crucial for developing safe and effective psychedelic-assisted therapies. They highlight the need for rigorous research to clarify how these compounds work and to optimize their clinical application.
Scientific Reports
April 15, 2026
Jacob S. Aday, Nicolas G. Glynos, Anne K. Baker et al.
A new questionnaire, the Psychedelic-related Major Life Changes Questionnaire (P-MLCQ), was developed to capture major life changes following psychedelic use that standard clinical measures miss. In a survey of 581 people who used psychedelics naturally, 83% reported at least one major life change influenced by their use, averaging 3.29 changes per person. The most common changes were in goals (54%), values (54%), and religion or spirituality (49%). These changes were rated highly positively on average. More frequent psychedelic use over the past five years was linked to more reported life changes. Women were 21% more likely than men to report changes, while older age and higher education were associated with fewer changes. The authors note that results may be influenced by positive bias and need replication in representative samples.
SSRN Electronic Journal
January 1, 2026
Dennis Parker Kelley, Gabriel Sturm, Katy Venable et al.
Serotonergic psychedelics show therapeutic effects across diverse neuropsychiatric, inflammatory, and cardiometabolic disorders, effects mediated largely by the serotonin 5-HT2A receptor. These drugs are exceptionally context-dependent, able to be anti-inflammatory or pro-inflammatory depending on setting. Each target pathology is linked to elevated stress exposure, which drives mitochondrial and allostatic dysregulation. The authors propose that psychedelics act as super-normal stimuli for the adaptive 5-HT2A receptor stress response, inducing a process called allostatic recalibration (AR). AR involves three phases: destabilizing, recalibrating, and consolidating updated allostatic programs. This recalibration replaces entrenched pathological allostatic programs with ones tuned to the safe context of psychedelic therapy, explaining their transdiagnostic effects.