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Exploring Serotonergic Psychedelics as a Treatment for Personality Disorders

Carrithers, Brennan M; Roberts, Daniel E; Weiss, Brandon M; King, Jacob D; Carhart-Harris, Robin L; Gordon, Alexandra R; Pagni, Broc A; Moreau, Miltiadis; Ross, Stephen; Zeifman, Richard J
Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.
PMID: 40081794
ISSN: 1873-7064
CID: 5808842

Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial

Pagni, Broc A; Zeifman, Richard J; Mennenga, Sarah E; Carrithers, Brennan M; Goldway, Noam; Bhatt, Snehal; O'Donnell, Kelley C; Ross, Stephen; Bogenschutz, Michael P
OBJECTIVE/UNASSIGNED:Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS/UNASSIGNED:Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS/UNASSIGNED:Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS/UNASSIGNED:PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.
PMID: 39741446
ISSN: 1535-7228
CID: 5779242

Psilocybin-assisted psychotherapy for existential distress: practical considerations for therapeutic application-a review

Kim, Arum; Halton, Barley; Shah, Akash; Seecof, Olivia M; Ross, Stephen
Existential distress is commonly experienced by patients diagnosed with a life-threatening illness. This condition has been shown to adversely impact quality of life and is correlated with increased suicidal ideation and requests for hastened death. While palliative care teams are experienced in treating depression and anxiety, existential distress is a distinct clinical condition for which traditional medications and psychotherapy approaches demonstrate limited efficacy or duration of effect. Psychedelic drugs, including psilocybin and lysergic acid diethylamide (LSD), in conjunction with psychotherapy have been shown to produce rapid and sustained reductions in existential and psychiatric distress and may be a promising treatment for patients facing existential distress in palliative care settings. In this narrative review article, we describe the history of psychedelic medicine including early studies and the modern wave of research over the past 20 years, which includes high quality clinical trial data. This review outlines specific considerations for therapeutic application of psilocybin including pharmacokinetics, patient selection, dosing, protocol designs, and safeguards to reduce potential adverse effects to help guide future psychedelic practitioners. With growing public interest and evolving state level policy reforms allowing access to psychedelic treatments, it is critical for palliative care providers to gain familiarity with the current state of science and the potential of psilocybin assisted psychotherapy in the treatment of existential distress.
PMID: 39168642
ISSN: 2224-5839
CID: 5680822

Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer

Petridis, Petros D.; Grinband, Jack; Agin-Liebes, Gabrielle; Kinslow, Connor J.; Zeifman, Richard J.; Bogenschutz, Michael P.; Griffiths, Roland R.; Ross, Stephen
ORIGINAL:0017662
ISSN: 2731-6076
CID: 5835022

Co-occurring Personality Disorders and Substance Use Disorders

Chapter by: Ross, Stephen; Demner, Adam; Roberts, Daniel; Petridis, Petros, Torres, Michael
in: The ASAM Principles of Addiction Medicine by Miller, Shannon C; Rosenthal, Richard; Levy, Sharon; Saxon, Andrew J, Tetrault, Jeanette M; Wakeman, Sarah E
Wolters Kluwer
pp. -
ISBN: 9781975201562
CID: 5702252

Older adults in psychedelic-assisted therapy trials: A systematic review

Bouchet, Lisa; Sager, Zachary; Yrondi, Antoine; Nigam, Kabir B; Anderson, Brian T; Ross, Stephen; Petridis, Petros D; Beaussant, Yvan
BACKGROUND/UNASSIGNED:Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder. AIMS/UNASSIGNED:The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. METHODS/UNASSIGNED:A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE. RESULTS/UNASSIGNED:4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. CONCLUSIONS/UNASSIGNED:While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.
PMID: 38240068
ISSN: 1461-7285
CID: 5628842

Psychedelic medicine in psychiatry residency training: a survey of psychiatric residency program directors

Yaden, Mary E.; Ching, Terence H.W.; Goldway, Noam; Roberts, Daniel E.; Hokanson, Jamila; Gukasyan, Natalie; Pittenger, Christopher; Kelmendi, Benjamin; Ross, Stephen; Glick, Gianni; O"â„¢Donnell, Kelley C.
Objective: The growth of psychedelic medicine creates new challenges in psychiatric education as physicians may soon be responsible for prescribing a number of psychedelic interventions. Despite this growing need for educated providers, very little is known about the training psychiatry residents receive in psychedelic medicine. We conducted a survey to determine the current educational opportunities as well as the priorities and concerns held by training directors about this emerging field. Methods: We emailed an online survey to US psychiatry residency training directors. Respondents answered questions about current offerings in psychedelic medicine, as well as their interest, priorities, and concerns about curricular materials and their delivery. Results: Sixty-one programs responded to our survey. The majority of respondents (64%) favored devoting additional time to psychedelic education, but many endorsed concerns about the dearth of educational materials (54%) and limited availability of faculty to deliver content (46%). The majority of programs (94%) expressed some interest in implementing a standardized curriculum in psychedelic medicine. Conclusion: Training directors recognized that their current curricular materials are limited, and they appeared interested in additional support to meet the upcoming demand in psychedelic education. Further research can inform curriculum development and implementation of psychedelic education in residency training.
SCOPUS:85203671316
ISSN: 0954-0261
CID: 5716542

Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder

Zeifman, Richard J; Kettner, Hannes; Ross, Stephen; Weiss, Brandon; Mithoefer, Michael C; Mithoefer, Ann T; Wagner, Anne C
PMCID:10769553
PMID: 38174611
ISSN: 2000-8066
CID: 5626092

NATURE MENTAL HEALTH

Petridis, Petros D.; Grinband, Jack; Agin-Liebes, Gabrielle; Kinslow, Connor J.; Zeifman, Richard J.; Bogenschutz, Michael P.; Griffiths, Roland R.; Ross, Stephen
ISI:001390110200010
CID: 5835012

Exploring the Potential Utility of Psychedelic Therapy for Patients With Amyotrophic Lateral Sclerosis

Gold, Noah D; Mallard, Austin J; Hermann, Jacob C; Zeifman, Richard J; Pagni, Broc A; Bogenschutz, Michael P; Ross, Stephen
PMID: 37167080
ISSN: 1557-7740
CID: 5509402