Nature
August 1, 2024
Joshua S Siegel, Subha Subramanian, Demetrius Perry et al.
241 citations
A single high dose of psilocybin (25 mg) massively disrupts functional connectivity in the human brain, causing more than threefold greater change than methylphenidate (40 mg). These changes are driven by desynchronization across spatial scales, dissolving network distinctions by reducing correlations within and anticorrelations between networks. The strongest effects occur in the default mode network, which is connected to the anterior hippocampus and is thought to create the sense of space, time, and self. Individual differences in connectivity changes are strongly linked to the subjective psychedelic experience. A persistent decrease in connectivity between the anterior hippocampus and default mode network lasts for weeks, suggesting a neuroanatomical correlate of the therapeutic and proplasticity effects of psychedelics.
Nature medicine
February 6, 2026
Joshua S Siegel, Conor Liston, Ginger E Nicol et al.
10 citations
Classic psychedelics, acting at the serotonin 5-HT2A receptor, alter brain function and consciousness. Research converges on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. Evidence of therapeutic response across neuropsychiatric indications is reviewed, integrating mechanistic findings. Challenges include discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms and clinical evidence linking subjective experience to therapeutic response, risks of enhanced neuroplasticity, and questions about trial design, scalability, and regulatory approval. The growth of psychedelic science may compel a rethinking of the relationship between subjective experience and biological change in psychiatry.
Translational Behavioral Medicine
October 17, 2024
Danielle R Adams, Heidi Allen, Ginger E Nicol et al.
7 citations
Psychedelic-assisted psychotherapy (PAT) shows promise for treating PTSD, depression, and substance use disorders, with potential FDA approval of psilocybin-assisted therapy for depression by 2026. This commentary calls for implementation scientists to collaborate with PAT researchers and practitioners to bring these treatments into routine practice, especially in safety-net settings like Federally Qualified Health Centers and Veterans Affairs health systems that serve historically marginalized populations. Using the RE-AIM Framework, the authors outline how implementation science can contribute tools, methodologies, and approaches to ensure PAT is safe, effective, and accessible for underserved communities.
The Journal of clinical psychiatry
June 10, 2026
Jacob T Steinle, Suraj Shankar, Joshua S Siegel et al.
After adjusting for preexisting psychiatric conditions, the link between hallucinogen use and psychosis disappears. Among 273,466 people with substance-related hospital admissions, psychosis diagnoses were more common after hallucinogen-related admissions (16.4%) than after other substance admissions (6.6%). However, once clinical characteristics were accounted for, the increased risk became nonsignificant (hazard ratio 0.97). This suggests that observed associations between hallucinogens and psychosis are largely due to underlying mental health vulnerabilities, not a direct causal effect. The findings inform psychedelic policy by indicating that population-level data on hallucinogen safety may reflect preexisting risk factors.