American Journal of Psychiatry最新文献

{"title":"Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression.","authors":"Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason","doi":"10.1176/appi.ajp.20230890","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230890","url":null,"abstract":"<p><p>Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but brief psychedelic intervention. The current paper reviews the clinical pharmacology of 5-MeO-DMT and DMT and their potential benefits and challenges in the treatment of depression. Both compounds display affinities for a variety of monoamine receptors and transporters, but mostly so for serotonergic (5HT) receptors, including 5HT_1A and 5HT_2A. Early clinical trials in small samples have shown that short interventions (15-30 min) with 5-MeO-DMT and DMT are safe and well tolerated and can induce marked improvement in symptoms of depression within 24 hours that sustain for at least 1 week. Data on long-term efficacy are currently scarce but do suggest a prolongation of the treatment response. Potential benefits of these treatments include flexible, single day dosing regimens, achievement of treatment efficacy independent from integrative therapy, and ease of clinical implementation. Future challenges include establishing the duration of the antidepressant effect and strategies on how to sustain the antidepressant response, optimization of treatment delivery parameters, and a mechanistic understanding of the clinical response. Acceptance of ultra-fast, short-acting psychedelics will depend on future randomized, placebo-controlled trials with a focus on replication, duration and maintenance of antidepressant efficacy in large patient samples.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"33-46"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelic Regulation Beyond the Controlled Substances Act: A Three-Dimensional Framework for Characterizing Policy Options.","authors":"Maha N Mian, Michael T Dinh, Allison R Coker, Jennifer M Mitchell, Brian T Anderson","doi":"10.1176/appi.ajp.20230787","DOIUrl":"10.1176/appi.ajp.20230787","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"6-9"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healing, Harms, and Humility: Expanding the Scope of Psychedelic-Assisted Psychotherapy Research.","authors":"Kelley C O'Donnell, Jim Grigsby, Charles S Grob","doi":"10.1176/appi.ajp.20230785","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230785","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"13-16"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial.","authors":"Scott T Aaronson, Andrew van der Vaart, Tammy Miller, Jeffrey LaPratt, Kimberly Swartz, Audrey Shoultz, Margo Lauterbach, Trisha Suppes, Harold A Sackeim","doi":"10.1176/appi.ajp.20231063","DOIUrl":"10.1176/appi.ajp.20231063","url":null,"abstract":"<p><strong>Objective: </strong>Depression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD.</p><p><strong>Methods: </strong>This was a 12-week, open-label trial conducted at Sheppard Pratt Hospital. Participants were 18-65 years of age, in a major depressive episode with documented insufficient benefit from at least five treatments during the current episode. A single dose of synthetic psilocybin (25 mg) was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing through at least 3 weeks post-dosing. Therapists met with patients for three sessions during pretreatment, during the 8-hour dosing day, and for three integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures including MADRS scores up to 12 weeks posttreatment, and subject-rated scales capturing depression and level of function were completed at baseline and all subsequent visits.</p><p><strong>Results: </strong>Twelve participants (six male, six female; mean age=40.6 years [SD=9.6]) with severe TRD were followed over the study period. Depressive symptoms were significantly decreased at week 3 (MADRS least-squares mean change=-15.8, 95% CI=-25.4 to -6.3) and Week 12 (MADRS least-squares mean change=-17.2, 95% CI=-25.2 to -9.1). In exploratory analyses, the Oceanic Boundlessness (OB) dimension of the psychedelic experience correlated with post-dosing antidepressant responses. Patients with comorbid PTSD (N=5) showed significantly less antidepressant effect of psilocybin.</p><p><strong>Conclusions: </strong>This open-label study suggests efficacy and safety of psilocybin in severe TRD and supports further study of psychedelics in this population, including consideration of PTSD interaction effects.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"104-113"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primum Non Nocere: The Onus to Characterize the Potential Harms of Psychedelic Treatment.","authors":"Sharmin Ghaznavi, Jeremy N Ruskin, Stephen J Haggerty, Franklin King, Jerrold F Rosenbaum","doi":"10.1176/appi.ajp.20230914","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230914","url":null,"abstract":"<p><p>The last few years have seen exponential growth in interest, investment, advocacy, and research into psychedelics as therapeutics. This reflects an optimism about the potential promise of psychedelics as therapeutics. As with all therapeutic interventions, research is needed not only into their benefits but also potential risks. Indeed, when substances with therapeutic potential are scrutinized over time, especially in broad populations with psychiatric and medical comorbidities typically excluded from clinical trials, and applied in less well-regulated or controlled settings, a greater understanding of the cautions emerges. Here, we review the literature on the known and potential harms, including enduring perceptual disturbances; triggering or enhancing the risk for onset of mania or psychosis; overuse, misuse, and dependence; challenging experiences or \"bad trips\"; risks associated with increased neuroplastic potential; and acute and cumulative cardiovascular effects. Each of these issues is addressed in this review, along with the call for continued research, including recommendations for further research and monitoring.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"47-53"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Translatable Biomarkers of Psychedelic-Induced Neuroplasticity.","authors":"David E Olson","doi":"10.1176/appi.ajp.20231054","DOIUrl":"10.1176/appi.ajp.20231054","url":null,"abstract":"","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"10-12"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDMA and MDMA-Assisted Therapy.","authors":"Aaron S Wolfgang, Gregory A Fonzo, Joshua C Gray, John H Krystal, Adrienne Grzenda, Alik S Widge, Nina V Kraguljac, William M McDonald, Carolyn I Rodriguez, Charles B Nemeroff","doi":"10.1176/appi.ajp.20230681","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230681","url":null,"abstract":"<p><p>MDMA (i.e., 3,4-methylenedixoymethamphetamine), commonly known as \"Ecstasy\" or \"Molly,\" has been used since the 1970s both in recreational and therapeutic settings. The Food and Drug Administration (FDA) designated MDMA-Assisted Therapy (MDMA-AT) as a Breakthrough Therapy for posttraumatic stress disorder (PTSD) in 2017, and the FDA is requiring an additional phase 3 trial after rejecting the initial New Drug Application in 2024. Unlike other psychedelics, MDMA uniquely induces prosocial subjective effects of heightened trust and self-compassion while maintaining ego functioning as well as cognitive and perceptual lucidity. While recreational use in nonmedical settings may still cause harm, especially due to adulterants or when used without proper precautions, conclusions that can be drawn from studies of recreational use are limited by many confounds. This especially limits the extent to which evidence related to recreational use can be extrapolated to therapeutic use. A considerable body of preliminary evidence suggests that MDMA-AT delivered in a controlled clinical setting is a safe and efficacious treatment for PTSD. After a course of MDMA-AT involving three MDMA administrations supported by psychotherapy, 67%-71% of individuals with PTSD no longer meet diagnostic criteria after MDMA-AT versus 32%-48% with placebo-assisted therapy, and effects endure at long-term follow-up. This review primarily aims to distinguish evidence of recreational use in nonclinical settings versus MDMA-AT using pharmaceutical-grade MDMA in controlled clinical settings. This review further describes the putative neurobiological mechanisms of MDMA underlying its therapeutic effects, the clinical evidence of MDMA-AT, considerations at the level of public health and policy, and future research directions.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"79-103"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compass Psychological Support Model for COMP360 Psilocybin Treatment of Serious Mental Health Conditions.","authors":"Namik Kirlić, Molly Lennard-Jones, Merve Atli, Ekaterina Malievskaia, Nadav L Modlin, Stephanie Knatz Peck, Alice Gaillard, Guy M Goodwin, Don Koelpin","doi":"10.1176/appi.ajp.20230884","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230884","url":null,"abstract":"<p><p>The psychedelic experience can be challenging. There is a need for a structured framework for providing psychological support to individuals with mental health conditions receiving investigational psilocybin treatment. The primary benefit of such a framework is to support a safe and meaningful psilocybin experience. It also enables future research on the facets of psychological support and/or psychotherapy that most optimally complement psilocybin treatment. The authors describe the Compass Psychological Support Model (CPSM), currently used to support participants with treatment-resistant depression in Compass-sponsored clinical trials of investigational COMP360 psilocybin treatment. The authors also outline the therapist training, mentoring, and fidelity assessment programs they have developed to ensure the quality and consistency of the CPSM delivery.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"126-132"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelics for the Treatment of Psychiatric Disorders: Interpreting and Translating Available Evidence and Guidance for Future Research.","authors":"Roger S McIntyre, Angela T H Kwan, Rodrigo B Mansur, Albino J Oliveira-Maia, Kayla M Teopiz, Vladimir Maletic, Trisha Suppes, Stephen M Stahl, Joshua D Rosenblat","doi":"10.1176/appi.ajp.20230902","DOIUrl":"https://doi.org/10.1176/appi.ajp.20230902","url":null,"abstract":"<p><p>During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder. Preliminary evidence also supports efficacy in other psychiatric disorders (e.g., tobacco and alcohol use disorders). Notwithstanding the interest and promise of psychedelics, concerns have arisen with respect to the interpretability and translatability of study results. For example, aspects related to short- and long-term safety, abuse liability, and the essentiality of the psychedelic \"trip\" and psychological support are, inter alia, insufficiently characterized with psychedelic agents. The overarching aims in this overview are 1) to review methodological aspects that affect inferences and interpretation of extant psychedelic studies in psychiatric disorders, and 2) to provide guidance for future research and development of psychedelic treatment in psychiatry, critical to study interpretation and clinical implementation.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"21-32"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial.","authors":"Broc A Pagni, Richard J Zeifman, Sarah E Mennenga, Brennan M Carrithers, Noam Goldway, Snehal Bhatt, Kelley C O'Donnell, Stephen Ross, Michael P Bogenschutz","doi":"10.1176/appi.ajp.20230887","DOIUrl":"10.1176/appi.ajp.20230887","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":"182 1","pages":"114-125"},"PeriodicalIF":15.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}