Journal of affective disorders
March 1, 2025
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
Journal of affective disorders
April 1, 2023
Nadav Liam Modlin, Tammy M Miller, James J Rucker et al.
30 citations
Psilocybin therapies show promise for conditions like major depressive disorder, end-of-life anxiety, and obsessive-compulsive disorder. However, little attention has been paid to intrapersonal and interpersonal factors that influence a patient's readiness for such interventions. This paper proposes that readiness assessment should include both intrapersonal and interpersonal factors to improve safety, patient care, and treatment outcomes. Although no reliable and valid instrument currently exists, the authors suggest three areas of focus—patient presentation, therapeutic alliance, and patient safety—to establish readiness and optimize and personalize psilocybin therapy.
American Journal of Psychiatry
January 1, 2025
Namik Kirlic, Molly Lennard-Jones, Merve Atli et al.
27 citations
A structured framework called the Compass Psychological Support Model (CPSM) provides psychological support for individuals with treatment-resistant depression receiving investigational psilocybin treatment in clinical trials. The model aims to ensure a safe and meaningful psychedelic experience and enables future research into which aspects of psychological support or psychotherapy best complement psilocybin treatment. The authors describe therapist training, mentoring, and fidelity assessment programs developed to maintain quality and consistency in delivering the CPSM.
Biological psychiatry. Cognitive neuroscience and neuroimaging
April 1, 2025
Saampras Ganesan, Fernando A Barrios, Ishaan Batta et al.
6 citations
Meditation practices, which have shown therapeutic benefits for conditions like depression, pain, addiction, and anxiety, have been studied with neuroimaging over the past decade. However, existing neuroscientific models are based on small, heterogeneous datasets, limiting generalizability and replicability. The ENIGMA-Meditation consortium is the first worldwide collaborative effort to conduct systematic meta- and mega-analyses of globally distributed neuroimaging data using standardized methods. This framework aims to improve statistical power and address multidomain heterogeneity in meditation practice types, experience, and experimental design. The consortium will generate rigorous neuroscientific insights into the mechanisms underlying meditation's therapeutic effects on psychological and cognitive attributes.
Translational psychiatry
July 13, 2025
Xiaoqian Yu, Aki Tsuchiyagaito, Masaya Misaki et al.
4 citations
Adolescents who experienced early life adversity (ELA) show greater difficulty down-regulating the posterior cingulate cortex (PCC), a key node of the default mode network, compared to healthy controls. A neurofeedback-augmented mindfulness training combining breath focus with real-time fMRI neurofeedback targeting the PCC was tested in 43 ELA-exposed and 40 healthy adolescents. Those with ELA were randomly assigned to active or sham neurofeedback. Both active and sham groups showed similar PCC down-regulation, and all adolescents reported increased state mindfulness after training. ELA-exposed adolescents reported greater improvements in positive affect, negative affect, and stress at one-week follow-up relative to controls, but there was no difference between active and sham neurofeedback on self-reported measures. The approach was feasible and acceptable for ELA-exposed adolescents but may not enhance mindfulness training beyond sham.
Frontiers in neuroscience
January 1, 2024
Kelly T Cosgrove, Aki Tsuchiyagaito, Zsofia P Cohen et al.
3 citations
A pilot study tested whether a single session of neurofeedback-augmented mindfulness training (NAMT) altered resting-state functional connectivity of the posterior cingulate cortex (PCC) in typically developing adolescents. Thirty-one adolescents (average age 14.8 years; 45% female) underwent resting-state fMRI before and after the NAMT task. The hypothesized decrease in connectivity between the PCC and other default mode network regions was not supported. However, functional connectivity between the PCC and a cluster including the left hippocampus and amygdala increased significantly after the task (Fisher's Z from 0.16 to 0.26). This preliminary finding suggests NAMT may strengthen connectivity between default mode and salience regions, potentially supporting self-referential and emotional processing.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
EClinicalMedicine
December 1, 2025
Nadav Liam Modlin, Victoria Williamson, Guy M Goodwin et al.
2 citations
Psilocybin treatment for post-traumatic stress disorder, when delivered with standardized preparation and support, may allow patients to engage with trauma-related material indirectly through affective, somatic, and self-transcendent experiences, such as feelings of unity or dissolution of self, rather than requiring direct confrontation with traumatic memories as in standard therapies. This qualitative study, nested within a phase 2 trial involving 21 adults with PTSD, identified four core themes: non-pharmacological factors for psychological safety and trust, the experiential nature of psilocybin treatment, engagement with trauma-related material, and comparative reflections on prior therapies. The findings suggest psilocybin offers a meaningful therapeutic opportunity, but larger controlled studies are needed.
April 8, 2024
Saampras Ganesan, Aki Tsuchiyagaito, Greg J. Siegle et al.
2 citations
preprint
Meditation practices, which have been adapted into manualized interventions for conditions like depression, pain, addiction, and anxiety, show therapeutic promise, but their neuroscientific basis remains unclear. Current neuroimaging studies rely on small, heterogeneous datasets that vary in practice types, participant experience, clinical targets, and imaging methods, limiting generalizability and replicability. To address this, the ENIGMA-Meditation consortium was formed as a global collaboration to conduct systematic meta- and mega-analyses of distributed neuroimaging data using standardized methods. This framework aims to improve statistical power and rigorously characterize the neural mechanisms underlying meditation's effects on psychological and cognitive attributes, advancing the field of contemplative neuroscience.
Therapeutic Advances in Psychopharmacology
June 8, 2025
Nadav Liam Modlin, Victoria Williamson, Carolina Maggio et al.
1 citation
PTSD is a common and debilitating condition that current treatments only partially address. This review examines psilocybin, a classical psychedelic, as a potential therapeutic agent. It synthesizes recent literature on psychedelic therapies for trauma-related conditions, including treatment-resistant depression and end-of-life anxiety. The authors propose a conceptual framework viewing PTSD as a maladaptive interpretive framework that psilocybin may disrupt through its psychopharmacological properties and subjective effects. A clinical narrative illustrates this process. Recommendations emphasize rigorous, trauma-informed protocols for safe administration in medical research settings.
Journal of Psychopharmacology
July 16, 2026
Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.
In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.
Journal of Clinical Psychopharmacology
December 9, 2025
Namik Kirlic, Merve Atli, Sunil Mistry et al.
In people with treatment-resistant depression who received a single dose of 25, 10, or 1 mg of COMP360 psilocybin, the drug dose was the strongest and most consistent predictor of the subjective psychedelic experience. Some pretreatment characteristics—such as positive affect, lower generalized anxiety symptoms, higher executive functioning, and greater personality disorder symptoms—had weak effects on different aspects of the experience. These findings suggest that pretreatment clinical characteristics are not major determinants of the acute psychedelic experience; dose remains the largest driver.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez et al.
correction
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