Faculty Bibliography

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.

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.

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.

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.

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.

IMPORTANCE:Psilocybin shows promise as a treatment for major depressive disorder (MDD). OBJECTIVE:To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. DESIGN, SETTING, AND PARTICIPANTS:In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. INTERVENTIONS:Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. MAIN OUTCOMES AND MEASURES:The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. RESULTS:A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. CONCLUSIONS AND RELEVANCE:Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03866174.

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.