Missouri medicine
January 1, 2023
Joshua S. Siegel, Craig S Pearson, Eric J Lenze
592 citations
New treatments for major depressive disorder are moving beyond traditional monoamine-targeting antidepressants toward options like κ-opioid antagonists, ketamine, and neurosteroids. These advances, combined with smartphone-based experience sampling and brain imaging, enable more precise diagnosis and symptom-specific measurement. This convergence heralds 'precision psychiatry'—selecting optimal treatments for individual patients. Anhedonia exemplifies this shift, evolving from a mere depression criterion to a transdiagnostic condition understood neurobiologically and targeted by novel pharmacotherapies. Functional testing of reward circuits in developing κ-opioid antagonists for anhedonia illustrates how other treatments, including psychedelics, may fit into future precision psychiatric care.
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.
Frontiers in Psychiatry
May 14, 2018
Ben J Palanca, Hannah R. Maybrier, Angela M. Mickle et al.
16 citations
Electroconvulsive therapy (ECT) deliberately induces generalized seizures to treat severe psychiatric illness, offering a chance to study how consciousness, cognition, and brain activity recover after seizures. Fifteen patients with treatment-resistant major depressive disorder will receive right unilateral ECT under etomidate anesthesia. They will then undergo three treatments in randomized order: etomidate plus ECT, ketamine plus ECT, and ketamine plus sham ECT, repeated for six total sessions. Cognitive tests assess sensorimotor speed, working memory, and executive function before and after each treatment. The study will measure time to return of responsiveness, cognitive recovery trajectories, postictal delirium, and EEG changes. It aims to develop biomarkers for tailoring cognitive and emotional recovery in ECT patients.
medRxiv
August 24, 2023
Subha Subramanian, Demetrius Perry, Caterina Gratton et al.
14 citations
preprint
Psilocybin disrupts connectivity across cortical networks and subcortical structures, producing more than three-fold greater acute changes in functional networks than methylphenidate. These changes are driven by desynchronization of brain activity across spatial scales, strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduces psilocybin-induced network changes, suggesting a neurobiological basis for grounding during psychedelic therapy. Psilocybin induces a persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after six months. This persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.
American Journal of Psychotherapy
May 6, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
7 citations
Practitioners of psychedelic therapy largely view physical touch as an important component of treatment, but they also emphasize strict professional boundaries and the necessity of patient consent. In a survey of 40 practitioners who had overseen an average of 41.4 psychedelic sessions, 70% agreed that therapeutic touch is crucial. However, most deemed specific forms of touch inappropriate: 63% considered bodywork inappropriate, and 98% considered full-body contact inappropriate. Free-response analysis showed 96% supported touching the patient's hand and 58% supported touching the shoulder. Unprompted, 63% of respondents stressed the importance of consent. These views may inform future practice.
Scientific Data
June 5, 2025
Subha Subramanian, Travis Rick Renau, Demetrius Perry et al.
4 citations
A psychedelic drug, psilocybin, and a comparison drug, methylphenidate, produce distinct acute and persistent changes in brain networks measurable with precision functional mapping, a technique that improves signal detection by repeatedly scanning individuals. Seven healthy adults underwent extensive baseline brain imaging, imaging shortly after drug intake, and follow-up scans for up to two weeks. Four participants repeated the psilocybin protocol months later. The dataset includes resting-state and task-based functional MRI, structural scans, and subjective experience reports. The authors release this resource to help researchers study how psilocybin and methylphenidate alter brain network organization over time.
Nat Hum Behav
February 24, 2025
Ginger E. Nicol, Danielle R Adams, Eric J Lenze et al.
4 citations
Psychedelic-assisted therapy (PAT) combines medication with psychotherapy, but many questions remain about how it works, for whom, and in what context. To avoid the typical 17-year delay between research and clinical practice, implementation science can help by simultaneously studying safety, effectiveness, and real-world delivery. Methods like sequential multiple assignment randomized trials (SMART), hybrid study designs, and fidelity measurement can speed implementation while maintaining quality and safety. Substantial changes to regulations, training, and access are needed to accommodate this multimodal therapy outside research settings. The authors advocate proceeding with accelerated caution.
The Journal of Clinical Psychiatry
February 5, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
3 citations
Practitioners who oversee psychedelic therapy sessions slightly prefer an 'emotive' approach—one that emphasizes human and spiritual elements—over a 'neuromodulatory' approach that focuses on biological drug effects. A survey of 40 qualified respondents from at least 4 countries, 11 U.S. states, and 16 institutions found no consensus on many psychological support strategies. Four key themes emerged: the importance of trust, the role of spirituality, creating an emotional setting, and conceptualizing negative experiences. Practitioners trained at the Multidisciplinary Association for Psychedelic Studies or the California Institute of Integral Studies showed a significantly stronger emotive preference than those trained elsewhere.
Psychopharmacology
October 27, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
Providers administering psychedelic drugs in clinical trials report a range of challenges, including intense dysphoria during sessions (42% of respondents), disappointment with the intervention (25%), and re-engaging with traumatic experiences (17%). An anonymous survey of 40 qualified respondents who oversaw 1656 psychedelic sessions identified 11 distinct themes of challenges. 70% of respondents felt that individuals with PTSD or prior trauma need additional psychological support, and they recommended an average of 9.8 hours of total psychological support for first-time recipients with serious mental illness. These findings highlight the need to incorporate potential adverse experiences into psychological support protocols for clinical trials and future guidelines.
Sports Medicine and Health Science
July 1, 2026
David Wing, Bart Roelands, Abraham Z. Snyder et al.
A narrative review of 30 studies examined how exercise, mindful movement, and mindfulness training affect resting state functional connectivity (rsFC) in the brains of non-clinical adults. Most studies reported changes in rsFC within the default mode, executive control, and salience networks. However, the largest and most methodologically rigorous study found minimal associations between rsFC and either exercise or mindfulness. Given the inconsistent results, caution is warranted in interpreting changes in rsFC attributable to these interventions. Methodological consistency in fMRI acquisition, data preparation, and analytical approaches is crucial to improve reproducibility and allow for comparison and aggregation.