The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
Frontiers in Pharmacology
January 1, 2022
Daniel Perkins, Broc A. Pagni, Jerome Sarris et al.
53 citations
Fifty-three first-time ayahuasca users (32 women, 21 men) completed questionnaires before and one month after a facilitated ceremony. Depression, anxiety, stress, alcohol and cannabis use, body dissociation, self-alienation, impulsivity, and negative affect significantly decreased, while positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and relationship satisfaction increased. Baseline traits—especially high negative emotionality and body dissociation, and low self-efficacy—strongly predicted improvements in mental health and substance use, whereas the intensity of the mystical experience had little predictive value. The findings suggest ayahuasca may produce broad mental health benefits and that personal traits could guide personalized treatment.
Scientific Reports
August 22, 2023
Hannes Kettner, Stephen Ross, Richard J. Zeifman et al.
31 citations
Co-using a low dose of MDMA with psilocybin or LSD is associated with less intense challenging experiences—such as grief and fear—and increased feelings of self-compassion, love, and gratitude, compared to using psilocybin or LSD alone. In a survey of 698 people planning to use these substances, the 27 who also took a low dose of MDMA reported these benefits without a reduction in mystical-type experiences or compassion. Medium-to-high MDMA doses did not show the same effects. The findings suggest MDMA may buffer against some difficult aspects of psychedelic experiences, but the study's small, non-experimental convenience sample limits certainty.
Scientific Reports
February 7, 2024
Broc A. Pagni, Petros Petridis, Samantha K. Podrebarac et al.
30 citations
In a small pilot study, patients with alcohol use disorder underwent functional magnetic resonance imaging before and after receiving either psilocybin or diphenhydramine. Psilocybin increased activity in the medial and lateral prefrontal cortex and left caudate, while decreasing activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. For negative emotional cues, psilocybin increased supramarginal gyrus activity; for positive cues, it increased right hippocampus activity and decreased left hippocampus activity. These brain changes suggest enhanced goal-directed action, improved emotional regulation, and diminished craving, but larger studies are needed to confirm the neural mechanisms of psilocybin-assisted therapy.
American Journal of Psychiatry
January 1, 2025
Noam Goldway, Snehal Bhatt, Stephen Ross et al.
23 citations
Psilocybin-assisted therapy (PAT) produced lasting changes in personality, indicating a normalization of abnormal personality trait expression in people with alcohol use disorder. The findings suggest that PAT may reduce impulsiveness, or that impulsive individuals may inherently respond better to the therapy. Further research is needed to clarify the mechanism.
Journal of psychiatry & neuroscience : JPN
January 1, 2023
Broc A. Pagni, Ethan Hill, Melissa J M Walsh et al.
20 citations
Mindfulness-based stress reduction (MBSR) and social support/education (SE) both reduced depression, anxiety, and autistic traits in adults with autism spectrum disorder (ASD). MBSR uniquely improved executive functioning and increased mindfulness traits, including the trait nonjudgment. Decreased connectivity between the insula and thalamus was associated with anxiety reduction and increased mindfulness traits specifically in the MBSR group; decreased connectivity between the prefrontal cortex and posterior cingulate correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral prefrontal cortex connectivity, which corresponded with reduced depression. The findings suggest shared and distinct neural mechanisms for MBSR and SE, implicating the default mode and salience networks.
Autism : the international journal of research and practice
June 1, 2024
Chad Stecher, Broc A. Pagni, Sara Cloonan et al.
11 citations
Autistic adults face elevated depression risk, which harms daily functioning and life outcomes. App-based meditation helps neurotypical adults manage depression, but long-term evidence for autistic adults was lacking. Anchoring, a habit-formation strategy, had not been tested in this group. This work shows that combining anchoring with app-based meditation is feasible and effective for establishing meditation habits in autistic adults. These habits maintained reduced depressive symptoms over six months. The findings indicate anchoring-based habit formation is a promising technique for building healthy habits in autistic adults, and app-based meditation offers a durable self-care option for managing depression in this population.
Autism : the international journal of research and practice
July 1, 2025
Nicole L Matthews, Melissa M Mitchell, Hannah Honda et al.
5 citations
A telehealth mindfulness program for autistic adolescents and their caregivers reduced depression symptoms in adolescents and anxiety symptoms in female adolescents. The MINDful TIME program included eight weekly group sessions via Zoom and regular use of a mindfulness meditation app. Forty-two adolescent-parent dyads were randomly assigned to the treatment or a delayed treatment control group. Ninety percent of treatment dyads completed the program, attending over 90% of sessions. Treatment adolescents showed large reductions in parent-reported depression symptoms compared to controls, and female adolescents showed reductions in anxiety symptoms. Parents reported improved mindfulness, well-being, and adolescent-parent relationship functioning.
Journal of Palliative Medicine
October 1, 2023
Noah D Gold, Austin J. Mallard, Jacob C Hermann et al.
5 citations
Psychedelic-assisted psychotherapy (PAP) may help alleviate psychiatric and existential distress in people with amyotrophic lateral sclerosis (ALS), a terminal neurodegenerative disease with an average survival of 3-4 years. The authors suggest PAP could also intervene on neuropathological dimensions of ALS, based on neuroprotective properties of psychedelics and robust improvements seen in other populations. They call for future preclinical trials in ALS models and rigorous clinical trials, given the lack of effective treatments for both disease progression and psychological distress.
Neuropharmacology
July 1, 2025
Brennan M. Carrithers, Daniel E. Roberts, Brandon M Weiss et al.
4 citations
Psychedelic therapy may hold potential for treating personality disorders by promoting adaptive changes in personality, though rigorous research is lacking. This review first examines research on psychedelics in individuals with personality disorders using the DSM-5-TR categorical model, then applies the dimensional DSM-AMPD framework to explore how psychedelics might affect self-functioning, interpersonal functioning, and pathological personality traits. The authors discuss clinical relevance, safety considerations, gaps, and recommendations for treating these complex populations.
Psychedelic Medicine
November 25, 2024
Noah D Gold, Broc A. Pagni, Petros Petridis et al.
3 citations
Psilocybin-assisted therapy may shift personal values in people with alcohol use disorder, specifically increasing Conservation—a value domain encompassing security and tradition. In a phase II trial, 93 participants received psychotherapy plus either psilocybin or an active placebo. Those given psilocybin showed significant increases in Conservation, security, and tradition values after treatment, while the placebo group did not. Certain features of the acute psychedelic experience, such as feelings of ineffability and reduced vigilance, correlated with these value changes. However, the shifts in values were not linked to changes in drinking behavior, suggesting that value modification alone does not drive reductions in alcohol use.
Research Square
October 15, 2024
Alexandra R. Gordon, Brennan M. Carrithers, Broc A. Pagni et al.
3 citations
Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.
Research Square
August 22, 2025
Richard J. Zeifman, George Danias, Gabrielle Agin-Liebes et al.
2 citations
Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder.
Journal of Clinical and Translational Science
April 1, 2024
Broc A. Pagni, Petros Petridis, Samantha K. Podrebarac et al.
1 citation
In a small pilot study, psilocybin, compared to diphenhydramine, altered brain activity in people with alcohol use disorder when they viewed alcohol and emotional images. Psilocybin increased activity in the medial and lateral prefrontal cortex and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices and cerebellum. For negative cues, psilocybin increased supramarginal gyrus activity; for positive cues, it increased right hippocampus activity and decreased left hippocampus activity. These changes suggest enhanced goal-directed action, improved emotional regulation, and diminished craving, warranting larger studies.
Journal of Humanistic Psychology
April 28, 2026
Austin J. Mallard, Matthew Broussard, Richard J. Zeifman et al.
People who have used psychedelics, either currently or in the past, report higher levels of compassionate love, self-compassion, and life satisfaction compared to those who have never used psychedelics. Current users also show greater self-compassion and life satisfaction than past users. Lifetime mystical-type experiences are positively linked to these aspects of positive psychological functioning across all groups, not just among psychedelic users. The findings, based on a cross-sectional survey of 984 people, suggest that psychedelic use and mystical experiences may support well-being, but the study is limited by self-reporting, its cross-sectional design, and a homogenous sample.
PsyArXiv
March 26, 2026
Broc A. Pagni, Stephen Ross, Sarah E. Mennenga et al.
preprint
An open-label extension of a Phase II randomized controlled trial examined the safety and efficacy of psilocybin-assisted therapy for alcohol use disorder. Participants who had received either psilocybin or placebo in the main trial were offered two open-label psilocybin sessions. The treatment was well tolerated, with no serious adverse events attributed to psilocybin. Heavy drinking days decreased substantially from baseline, and the reduction was sustained through the 32-week follow-up. The findings suggest that psilocybin-assisted therapy may produce durable reductions in alcohol consumption among individuals with alcohol use disorder.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.