November 6, 2023
Jacob S. Aday, David P Horton, Gisele Fernandes‐osterhold et al.
5 citations
preprint
Psychedelic-assisted psychotherapy (PAP) combines a psychedelic substance with psychotherapeutic support, yet the specific role and necessary components of the psychotherapy itself remain understudied. This review examines current PAP clinical trial models and theoretical frameworks, then draws lessons from traditional psychotherapy research on standardizing treatments, identifying mechanisms of change, and optimizing trial designs. The authors conclude that PAP is a unique transdisciplinary intervention and call for increased research on its psychotherapeutic component to inform best practices and federal guidelines.
Psychedelic Medicine
February 28, 2024
Joshua Woolley, Amanda E. Downey, Ellen Bradley et al.
2 citations
A risk stratification tool is proposed to help decide whether individuals with a family history of bipolar disorder should be included in psilocybin therapy trials. The authors argue for caution due to the potential for serious adverse events, but they recommend against outright exclusion. The tool allows for more nuanced inclusion and exclusion criteria, balancing the need for effective treatments against safety concerns.
August 25, 2024
Stephanie L. Haft, Amanda E. Downey, Marissa Reymond-Flesch et al.
1 citation
preprint
Limited participant diversity in mental health intervention research perpetuates health disparities, a concern especially relevant to psychedelic-assisted psychotherapy (PAT). This systematic review of 21 randomized controlled trials of psilocybin- and MDMA-assisted therapies (total 1,034 participants) found that gender (100%) and race or ethnicity (76%) were frequently reported, while socioeconomic status was sometimes reported (57%) using varied measures. Sexual orientation (9.5%) and immigration status (4.8%) were rarely reported, and no studies reported gender identity. Black/African-American (12.2%) and Hispanic/Latino (7.2%) participants were significantly underrepresented compared to the US population and non-psychedelic clinical trials. MDMA trials enrolled more diverse samples than psilocybin trials. Analyses of treatment effects by sociodemographic variables were virtually nonexistent, highlighting the need for inclusive recruitment and rigorous reporting to improve generalizability.
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.