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.
Psychopharmacology
January 13, 2022
David A Bender, David J Hellerstein
82 citations
A review of studies since 1991 identified 14 clinical trials of classical psychedelics—11 of psilocybin (257 participants), 1 of LSD (12 participants), and 2 of ayahuasca (46 participants). Published studies largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation of symptoms for multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have limitations including small sample sizes, difficulty in blinding, limited follow-up, and highly screened treatment populations. The ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial.
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.
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.
BJPsych Open
February 12, 2026
David A Bender, Holly Dunn, Amanda Pekau et al.
1 citation
From 2000 to 2025, media coverage of psychedelic drugs increasingly focused on their therapeutic potential, rising from 13.3% of articles in 2000–2009 to 85.3% in 2020–2025. Overall sentiment was positive, with an average score of 78.5 out of 100. However, negative and neutral coverage has grown since 2020: the proportion of articles with sentiment scores of 65 or below rose from 3.6% in 2020 to 20.9% in 2024, and average sentiment dropped significantly in 2024 compared to 2020–2023. Artificial intelligence sentiment ratings closely matched human ratings.
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.