Searched for: person:bogenm02 or rosss01 or odonnk02 or roberd13 or hux02 or siegej08
A Multi-Site Evaluation of a Psychedelic Medicine Curriculum for Psychiatry Trainees
Yaden, Mary E; O'Donnell, Kelley C; Roberts, Daniel E; Goldway, Noam; Tiwari, Praachi; Ching, Terence H W; Hokanson, Jamila; Gukasyan, Natalie; Appold, Brendan; Glick, Giancarlo; Kelmendi, Benjamin; Ross, Stephen; Pittenger, Christopher
OBJECTIVE:Interest in psychedelic medicine is increasing, yet psychiatry trainees report limited education in this area. The authors developed a standardized curriculum and evaluated its impact on trainee knowledge and attitudes toward psychedelic medicines. METHODS:A 6-h psychedelic medicine course was delivered across four psychiatry residency programs in the Northeast United States in 2025-2026. The curriculum included six modules covering foundational concepts and evidence, as well as clinical considerations. Anonymous pre- and post-course surveys assessed knowledge, interest, and confidence in counseling. Statistical comparisons were used to evaluate pre-post changes. RESULTS:Forty trainees participated across institutions; 34 completed a pre-course survey and 22 completed a post-course survey. Most trainees reported minimal prior didactic exposure to psychedelic medicine. Self-assessed knowledge as well as scores on a knowledge quiz improved significantly following the course. Self-rated understanding of both the rationale for psychedelic treatments and limitations of evidence increased. Most substantially, confidence in counseling patients about clinical research, harm reduction, and treatment risks improved across domains. Baseline interest in psychedelic medicine was high at the start of the course and did not change significantly following its completion. CONCLUSIONS:A multi-site curriculum in psychedelic medicine was associated with increased knowledge and counseling confidence in trainees. The curriculum did not significantly impact interest or plans to pursue opportunities in psychedelic medicine, suggesting the course did not overinflate enthusiasm for the field. Standardized curricula in residency education may help address gaps in psychiatric training as clinicians increasingly encounter questions about these emerging treatments.
PMID: 42778871
ISSN: 1545-7230
CID: 6073487
Long-Term Mental Health and Wellbeing Outcomes Associated with Naturalistic Ayahuasca Consumption
Pagni, B A; Halman, A; Sarris, J; Chenhall, R; Bogenschutz, M P; Perkins, D
The durability of ayahuasca's effects on mental health and the influence of clinical diagnoses on therapeutic response is unclear. Adults with no prior exposure to ayahuasca (n = 66) participating in neo-shamanic ayahuasca ceremonies completed questionnaires at baseline, 7 days, and 1, 6, and 12 months. Mixed models were used to characterize temporal trajectories in mental health, alcohol and cannabis use, affect, personality, spirituality, and relationships and examine the longevity of effects in individuals with and without a depressive or anxiety disorder. After multiple comparison correction, ayahuasca use was associated with decreases in depression, anxiety, stress, negative affect, negative emotionality, acceptance of external influence, and self-alienation at all time points. Improvements in mental health, self-efficacy, and spirituality were observed up to 12 months post-ceremony. Individuals with depression and anxiety diagnoses maintained significant symptom reductions, whereas those without a diagnosis experienced short-term benefits. Decreases in alcohol and cannabis use were only observed at month 1. Naturalistic ayahuasca use was associated with persisting improvements in mental health and wellbeing, with the largest magnitude of symptom reduction observed in those diagnosed with a depressive or anxiety disorder. Differing trajectories of change were identified across psychological constructs, suggestive of both enhancement and attenuation of gains over time.
PMCID:12353293
PMID: 39980134
ISSN: 2159-9777
CID: 6072853
The intersection between psychedelics and schizophrenia spectrum disorders: Reevaluating risk and therapeutic potential
Brar, Pavan S; Price, Rebecca B; Ross, Stephen; Tofighi, Babak; Sarpal, Deepak K
In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.
PMID: 42345450
ISSN: 1461-7285
CID: 6056082
An international mega-analysis of psychedelic drug effects on brain circuit function
Girn, Manesh; Doss, Manoj K; Roseman, Leor; Preller, Katrin H; Palhano-Fontes, Fernanda; Pasquini, Lorenzo; Barrett, Frederick S; Mallaroni, Pablo; Mason, Natasha L; Timmermann, Christopher; McCulloch, Drummond E; Fisher, Patrick M; Winston, Brian S; Moujaes, Flora; Muller, Felix; Liechti, Matthias E; Vollenweider, Franz X; Ramaekers, Johannes G; Kuypers, Kim; Araujo, Draulio B; Sporns, Olaf; Siegel, Joshua; Dosenbach, Nico; Nutt, David J; Carhart-Harris, Robin L; Stamatakis, Emmanuel A; Bzdok, Danilo
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research.
PMID: 41942645
ISSN: 1546-170x
CID: 6025162
The science of psychedelic medicine
Siegel, Joshua S; Liston, Conor; Nicol, Ginger E; Carhart-Harris, Robin L; Bogenschutz, Michael P
Classic psychedelics typically act at the serotonin 5-HT2A receptor to profoundly alter brain function and consciousness. Research on these compounds has accelerated. Major strides have been made in understanding their unique mechanisms of action and clinical potential. This Review outlines the state of psychedelic science, spanning cellular mechanisms, systems neuroscience and clinical investigation. We show that preclinical and human research findings converge on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. We review evidence of therapeutic response across neuropsychiatric indications and consider how this integrates with mechanistic findings. We also explore challenges and opportunities, including discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms, and clinical evidence linking the subjective experience to therapeutic response; the risks inherent to enhanced neuroplasticity; and questions surrounding trial design, scalability and regulatory approval. The growth of psychedelic science and medicine may compel a fundamental rethinking of the relationship between subjective experience and biological change in psychiatry.
PMID: 41652120
ISSN: 1546-170x
CID: 6000732
Effects of cannabidiol in alcohol use disorder patients with and without co-occurring post-traumatic stress disorder: Tolerability but no evidence for efficacy in two randomized proof-of-concept trials
Bogenschutz, Michael P; Blessing, Esther; Dgheim, Danielle; Cho, Dayeon; Zhang, Jun; Laska, Eugene M; Marmar, Charles R
BACKGROUND:Comorbidity between alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) exacerbates symptom severity and worsens treatment outcomes. Limited clinical research suggests that cannabidiol (CBD) may have therapeutic effects on anxiety disorders and addictive behavior, but efficacy has not been established. METHODS:Two proof-of-concept trials of CBD were conducted simultaneously. In Study 1, 27 adults with moderate to severe AUD were randomized to CBD [600 mg/day for 4 weeks, then 1200 mg/day for 4 weeks] versus placebo. In Study 2, 30 adults with AUD plus DSM-5 PTSD or subthreshold post-traumatic stress disorder (PTSD) were randomized to CBD 600 mg/day vs. placebo for 6 weeks. The trials assessed CBD pharmacokinetics, safety and tolerability, alcohol consumption, craving, mood and anxiety symptoms, and, in Study 2, PTSD symptom severity. Efficacy analyses used mixed-effects models, and the primary drinking outcome was the average number of drinks per day during treatment. RESULTS:CBD was rapidly absorbed, achieving near-steady-state trough levels by week 1, with dose-dependent increases during weeks 5-8 in Study 1. Mean trough and estimated peak CBD levels at week 4 (n = 20) were 31.15 (SD: 21.22) ng/mL and 130.75 (SD: 152.57) ng/mL, respectively. Few safety concerns emerged, but 7/31 (22.6%) of participants assigned to CBD experienced dose-limiting side effects. In both studies, participants in both treatment groups showed large reductions in drinks per day and percentage heavy drinking days during treatment (Cohen's dz. > 0.9). Neither trial demonstrated superiority of CBD over placebo for drinking outcomes, craving, mood, anxiety, or PTSD symptoms. CONCLUSIONS:These findings support the feasibility and tolerability of twice-daily oral CBD up to 1200 mg/day in actively drinking individuals but do not demonstrate efficacy at the CBD levels that were achieved in this study. Further dose finding and larger, well-powered trials are needed to clarify CBD's therapeutic potential in AUD and comorbid PTSD.
PMID: 41312717
ISSN: 2993-7175
CID: 5968792
Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice
Hu, Xiaojue; Gorman, Ingmar; Nielson, Elizabeth
Psychedelic Harm Reduction and Integration (PHRI) is a transtheoretical clinical model for working with psychedelic experiences in therapeutic settings. Drawing from harm reduction psychotherapy, psychedelic-assisted therapy, mindfulness-based modalities, and psychodynamic therapy, PHRI offers a framework for clinicians to assist clients in preparing for and integrating psychedelic experiences without directly administering psychedelics. This approach emphasizes non-pathologizing, client-empowering strategies to address both challenging and positive psychedelic experiences. PHRI incorporates principles such as non-directive and inner-directed approaches, somatic awareness, and psychological flexibility. The model addresses common integration challenges including fear, ego dissolution, and increased emotional sensitivity. By bridging various therapeutic modalities, PHRI aims to support clients in translating psychedelic experiences into enduring positive changes while decreasing potential harms. This chapter outlines the theoretical foundations of PHRI, distinguishes it from existing approaches, and explores its application in clinical practice, with a focus on the integration phase of psychedelic experiences.
PMID: 39654004
ISSN: 1866-3370
CID: 5762442
Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions
Griffiths, Roland R; Jesse, Robert; Richards, William A; Johnson, Matthew W; Sepeda, Nathan D; Bossis, Anthony P; Ross, Stephen
BACKGROUND/UNASSIGNED:Although historical writings, anthropological accounts, and experimental studies document associations between psilocybin use and religion, no prospective experimental study has investigated how the effects of psilocybin are experienced and interpreted by religious clergy. This exploratory study evaluated the overall safety and the acute and enduring effects of psilocybin in clergy. METHODS/UNASSIGNED:= 16) at 6 months after screening using self-report measures. The effects of psilocybin were also assessed on session days and 4 and 16 months after the second psilocybin session in the 24 participants who completed both sessions. RESULTS/UNASSIGNED:The primary outcome assessment at 6 months after screening showed that, compared with the delayed control group, participants who had received psilocybin reported significantly greater positive changes in their religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in their non-religious attitudes, moods, and behavior. Follow-up assessments showed that positive changes in religious and non-religious attitudes and behavior were sustained through 16 months after the second psilocybin session. At that time, participants rated at least one of their psilocybin experiences to be among the top five most spiritually significant (96%), profoundly sacred (92%), psychologically insightful (83%), and psychologically meaningful (79%) of their lives. Furthermore, 42% rated one of their experiences to be the single most profound of their lifetime. At 16-months follow-up, most (79%) strongly endorsed that the experiences had positive effects on their religious practices (e.g., prayer or meditation) and their daily sense of the sacred, and most (71%) reported positive changes in their appreciation of religious traditions other than their own. Although no serious adverse events were reported, 46% rated a psilocybin experience as among the top five most psychologically challenging of their lives. CONCLUSIONS/UNASSIGNED:In this population of clergy, psilocybin administration was safe and increased multiple domains of overall psychological well-being including positive changes in religious attitudes and behavior as well as their vocation as a religious leader. The study was limited by a waitlist control design, homogenous sample, and the use of some unvalidated outcome measures. Further research with more rigorous control conditions and diverse samples is needed.
PMCID:13000417
PMID: 41869007
ISSN: 2831-4433
CID: 6017792
The Effect of Psychedelics on Individuals with a Personality Disorder: Results from Two Prospective Cohort Studies
Gordon, Alexandra R.; Carrithers, Brennan M.; Pagni, Broc A.; Kettner, Hannes; MRes, Alessia Marrocu; Nayak, Sandeep M.; Weiss, Brandon M.; Carhart-Harris, Robin L.; Roberts, Daniel E.; Erritzoe, David; Garcia-Romeu, Albert; Jackson, Heather; Lowe, Matthew X.; Zeifman, Richard J.
ORIGINAL:0017852
ISSN: 2831-4425
CID: 5980002
Exploring the role of gender on treatment outcomes in older adults with alcohol use disorder
Tryggedsson, Jeppe Sig Juelsgaard; Andersen, Kjeld; Behrendt, Silke; Bogenschutz, Michael P; Buehringer, Gerhard; Søgaard Nielsen, Anette
BACKGROUND:Alcohol use disorder (AUD) among older adults, particularly with respect to gender differences in treatment outcomes, remains underexplored. Our objective was to explore gender differences in AUD treatment outcomes among older adults, focusing on continuous measures (e.g., drinks per day) and binary measures (e.g., abstinence) across a 1-year period. METHODS:We analyzed data from a multinational randomized controlled trial involving 693 older adults (60+) diagnosed with DSM-5 AUD. Participants received motivational enhancement therapy and the community reinforcement approach, across sites in Denmark, Germany, and the United States. Participants were assessed at baseline and after 4, 12, 26, and 52 weeks. Multilevel mixed-effects linear and logistic regressions were used, adjusted for sociodemographic and baseline drinking characteristics. RESULTS:Both men and women showed significant improvements across all outcomes. At baseline, females reported 0.75 fewer drinks/day, 1.33 fewer drinks/drinking day, and 50% lower odds of low blood alcohol content (BAC) compared to males (OR = 0.50; p < 0.05). Gender-time interactions showed smaller reductions in females' drinks per day and drinks per drinking day (p < 0.05), resulting in similar drinking levels at follow-ups. No gender differences were found at any time points for percent days abstinent and percent heavy drinking days (p ≥ 0.05). A significant gender-time interaction was found for percent days abstinent (p = 0.04), but no consistent direction was observed across time points. For abstinence and no heavy drinking, no gender differences were found (p ≥ 0.05). No interactions between gender and time were found for any binary outcome (p ≥ 0.05). CONCLUSIONS:Among older adults with DSM-5 AUD diagnosis, treatment led to substantial and sustained improvements across genders. While women showed less favorable drinking reductions, adjusted estimates were broadly comparable. Given women's increased physiological vulnerability to alcohol, this may not imply equivalent clinical risk. Still, findings support the potential for meaningful treatment benefits regardless of gender.
PMCID:12638275
PMID: 40930847
ISSN: 2993-7175
CID: 5969482