psilocybin

In April 2026, US President Donald Trump signed an executive order fast-tracking access to psilocybin and ibogaine for the treatment of serious mental illness. This follows decades in which psychedelics had been vilified as a group of drugs entirely lacking in therapeutic potential, associated with counter-cultural groups such as hippies, and whose use was both criminalised and widely stigmatised. Our central questions are: How have the substances, practices, understandings and relationships that comprise psychedelic use developed, and shifted, over time? And how might we best understand the overall structure and dynamics of such changes? We argue that the recent psychedelic renaissance cannot be understood as the simple ‘discovery’ of a therapeutic potential that previously lay dormant in the substances themselves. It is better grasped as a part-process of longer-term informalisation processes, bound up with shifting balances of power between established and outsider groups and with the changing behavioural and emotional standards – the social canons – through which psychedelic use has become refigured. Drawing on the figurational sociology of Norbert Elias and relational work on substance use and health, we trace the shift in psychedelics from counter-cultural sacrament to therapy and technology of the self. Through dialogue with a multimodal, multi-source evidential base, we develop the concept of ‘pharmaceuticalisation from below’ to characterise both the contemporary uptake of psychedelics and the broader figurational dynamics this expresses.

Background Psychedelic retreats are increasingly used to promote wellbeing outside clinical settings, yet the psychological processes associated with sustained improvements in wellbeing remain poorly understood. From a public mental health perspective, identifying mechanisms that support positive mental health beyond symptom reduction is of growing importance. Methods This naturalistic longitudinal study followed 173 participants attending guided psilocybin retreats conducted within a structured framework of preparation, dosing, and integration. Mental wellbeing was reported before the retreat and across a 12-month follow-up period. Longitudinal changes were examined using linear mixed-effects models. Mediation analyses investigated whether changes in connectedness, neuroticism (anxiety facet), spiritual transcendence, and absorption were associated with changes in wellbeing. Mystical-type experiences were examined as potential predictors of these psychological changes. Results Participants reported substantial and sustained improvements in mental wellbeing over 12 months, moving from levels below Swedish population norms at baseline toward comparable levels at follow-up. Connectedness showed the strongest statistical association with improvements in wellbeing and accounted for the largest proportion of variance in wellbeing change, followed by reductions in the anxiety facet of neuroticism and absorption. Spiritual transcendence was associated with wellbeing improvements when examined separately but did not retain unique effects in the multiple mediation model. More intense mystical-type experiences predicted greater increases in connectedness, spirituality, and absorption, as well as greater reductions in neuroticism (trait anxiety). The association between mystical experiences and wellbeing was substantially attenuated when connectedness was included in the model, suggesting that connectedness may act as a candidate mediator linking mystical-type experiences to longer-term wellbeing, though the observational design precludes causal inference. Conclusions These findings extend prior work on psychedelic-assisted therapy to naturalistic retreat settings, suggesting that connectedness may represent a key psychological process linking psychedelic retreat experiences to sustained improvements in mental wellbeing. From a public mental health perspective, the results highlight the potential importance of social and relational factors in promoting wellbeing beyond the treatment of mental illness. Future controlled studies are needed to clarify the relative contributions of psychedelic, social, and contextual components.

Background Clinical research on psychedelic-assisted therapy (PAT) has expanded substantially in recent years, particularly for post-traumatic stress disorder (PTSD) and depressive disorders. Contemporary studies have generally evaluated psychedelic administration within controlled therapeutic settings that include psychological support, preparation, and integration. However, variability in clinical response and methodological challenges have highlighted the importance of individual, relational, and contextual factors, often described as “set and setting,” in understanding therapeutic outcomes. The role of psychotherapy and the broader therapeutic context therefore remains an important area of investigation. Objective This scoping review aimed to map the contemporary evidence on PAT, characterize the clinical and psychotherapeutic approaches used with psilocybin, MDMA, LSD, and DMT, summarize reported clinical and safety findings, and identify methodological, mechanistic, ethical, and implementation considerations across existing protocols. Methods A structured search of PubMed, PsycINFO, Scopus, and ClinicalTrials.gov was conducted on 23 February 2026. Sources published or publicly available between January 2020 and November 2025 were eligible. The review included peer-reviewed and relevant non-peer-reviewed sources addressing psychedelic-assisted interventions, including primary clinical studies, reviews, clinical trial registrations, regulatory documents, and other relevant contextual sources. Records were managed using Zotero and screened against predefined Population, Concept, and Context criteria. Findings were synthesized descriptively according to source type and evidence domain. Results The mapped evidence was most developed for MDMA-assisted therapy in PTSD and psilocybin-assisted interventions for depressive disorders. Randomized clinical trials reported reductions in PTSD and depressive symptoms following MDMA- and psilocybin-based interventions, respectively, while emerging clinical evidence also investigated LSD-based treatment for generalized anxiety disorder. Evidence for DMT-assisted therapy remained comparatively preliminary, with several available sources consisting of trial registrations or industry-reported information. Across the literature, preparation, supervised psychedelic administration, and integration were common therapeutic components, although the structure and intensity of psychotherapy varied substantially. Functional unblinding, expectancy effects, heterogeneity of psychotherapeutic approaches, and limitations in long-term safety data were recurring concerns. Ethical issues included informed consent during altered states of consciousness, therapist competence and boundaries, cultural considerations, and equitable access. Conclusion PAT represents a rapidly developing area of clinical research, but the evidence base remains heterogeneous across compounds, indications, therapeutic models, and levels of evidential maturity. Future research should improve the standardization and reporting of psychotherapeutic interventions, strengthen methods for assessing blinding and expectancy, establish consistent long-term safety monitoring, and develop robust ethical and equity frameworks. Clear distinction between peer-reviewed clinical findings and preliminary or contextual evidence will also be essential as PAT research progresses toward broader clinical implementation.

Background: Classic psychedelics, including LSD, psilocybin, and N,N-dimethyltryptamine (DMT)/ ayahuasca, have shown promise as rapid-acting treatments for psychiatric disorders. Because sleep plays a central role in emotional regulation and neuroplasticity, psychedelic-induced changes in sleep architecture are of interest.Methods: A systematic review was conducted following PRISMA guidelines. PubMed was searched for preclinical and clinical studies published up to May 1, 2026, investigating psychedelics and sleep-related outcomes. Twelve eligible studies evaluated LSD, psilocybin, or DMT/ayahuasca and assessed sleep architecture, sleep quality, electroencephalographic activity, or dreams. Study validity was assessed using appropriate methodological tools.Results: Preclinical studies consistently demonstrated acute REM sleep suppression, delayed REM onset, increased wakefulness, and transient disruption of non-REM sleep. Human findings were more heterogeneous, although randomized trials reported prolonged REM latency after psilocybin and reduced REM duration after ayahuasca. Evidence regarding slow-wave activity (SWA) was mixed, with ayahuasca increasing early-cycle SWA and psilocybin reducing absolute delta power during the first sleep cycle. Subjective sleep quality showed little acute change in controlled trials, whereas one large naturalistic study reported reductions in sleep disturbances following psilocybin. Administration close to bedtime appeared more disruptive than daytime dosing. In general, quality assessments indicated fair-to-poor validity and notable risk of bias.Conclusions: Classic psychedelics produce acute but transient alterations in sleep physiology, particularly affecting REM sleep. Whether these changes contribute to therapeutic effects remains uncertain. Larger, well-controlled studies using standardized polysomnographic methods are needed to clarify the relationship between psychedelic-induced sleep modulation and clinical outcomes. This review was not prospectively registered.

زمینه: سایکدلیک‌های کلاسیک، از جمله LSD، سیلوسایبین و N,N-dimethyltryptamine (DMT)/آیاهواسکا، به عنوان درمان‌های سریع‌الاثر برای اختلالات روان‌پزشکی امیدبخش ظاهر شده‌اند. از آنجا که خواب نقش مرکزی در تنظیم هیجانی و نوروپلاستیسیتی ایفا می‌کند، تغییرات ناشی از سایکدلیک‌ها در معماری خواب مورد توجه قرار گرفته است. روش‌ها: یک مرور نظام‌مند مطابق با دستورالعمل‌های PRISMA انجام شد. پایگاه PubMed برای مطالعات پیش‌بالینی و بالینی منتشرشده تا ۱ مه ۲۰۲۶ که به بررسی سایکدلیک‌ها و پیامدهای مرتبط با خواب پرداخته بودند، جست‌وجو شد. دوازده مطالعه واجد شرایط LSD، سیلوسایبین یا DMT/آیاهواسکا را ارزیابی کرده و معماری خواب، کیفیت خواب، فعالیت الکتروانسفالوگرافیک یا رؤیاها را سنجیده‌اند. روایی مطالعات با استفاده از ابزارهای روش‌شناختی مناسب ارزیابی شد. یافته‌ها: مطالعات پیش‌بالینی به طور مکرر سرکوب حاد خواب REM، تأخیر در شروع REM، افزایش بیداری و اختلال گذرا در خواب غیر REM را نشان دادند. یافته‌های انسانی ناهمگن‌تر بودند، هرچند کارآزمایی‌های تصادفی‌شده تأخیر طولانی‌تر در شروع REM پس از سیلوسایبین و کاهش مدت REM پس از آیاهواسکا را گزارش کردند. شواهد مربوط به فعالیت موج آهسته (SWA) متناقض بود، به طوری که آیاهواسکا SWA چرخه ابتدایی را افزایش داد و سیلوسایبین توان دلتا مطلق را در اولین چرخه خواب کاهش داد. کیفیت خواب ذهنی در کارآزمایی‌های کنترل‌شده تغییر حاد اندکی نشان داد، در حالی که یک مطالعه طبیعی‌نگر بزرگ کاهش اختلالات خواب پس از سیلوسایبین را گزارش کرد. مصرف نزدیک به زمان خواب نسبت به مصرف در طول روز مخرب‌تر به نظر می‌رسید. به طور کلی، ارزیابی کیفیت مطالعات نشان‌دهنده روایی متوسط تا ضعیف و خطر سوگیری قابل توجه بود. نتیجه‌گیری: سایکدلیک‌های کلاسیک تغییرات حاد اما گذرایی در فیزیولوژی خواب ایجاد می‌کنند که به ویژه خواب REM را تحت تأثیر قرار می‌دهد. این که آیا این تغییرات در آثار درمانی نقش دارند یا خیر، همچنان نامشخص است. مطالعات بزرگ‌تر و با کنترل مناسب با استفاده از روش‌های استاندارد پلی‌سومنوگرافی برای روشن شدن رابطه میان تعدیل خواب ناشی از سایکدلیک‌ها و پیامدهای بالینی مورد نیاز است. این مرور به طور پیش‌نگر ثبت نشده است.

Obsessive-compulsive disorder (OCD) is a highly debilitating and often chronic condition. A large percentage of patients do not respond to first-line treatments with selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy (CBT), underscoring the need for novel therapeutic approaches. In this context, promising innovative treatments have recently emerged for OCD; these include pharmacological options such as ketamine and psilocybin—which may exert rapid-acting effects—as well as neuromodulatory treatments such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS). In addition, growing evidence links early life stress with neuroinflammatory pathways and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in OCD, opening novel treatment targets. While preliminary clinical trials of novel rapid-acting substances in OCD are encouraging, results are mixed and evidence of repeated dosing is scarce. This narrative review synthesizes current evidence on rapid-acting and neuromodulatory treatments for OCD, with a particular focus on stress-related mechanisms, offering new therapeutic possibilities as well as avenues for future research.

اختلال وسواس فکری-عملی یک وضعیت بسیار ناتوان‌کننده و اغلب مزمن است. درصد بالایی از بیماران به درمان‌های خط اول با مهارکننده‌های بازجذب سروتونین انتخابی (SSRIs) یا درمان شناختی-رفتاری (CBT) پاسخ نمی‌دهند که این امر بر نیاز به رویکردهای درمانی نوین تأکید دارد. در این زمینه، درمان‌های نوآورانه و امیدبخشی اخیراً برای اختلال وسواس فکری-عملی مطرح شده‌اند؛ این درمان‌ها شامل گزینه‌های دارویی مانند کتامین و سیلوسایبین—که ممکن است اثرات سریع‌الظهور داشته باشند—و همچنین درمان‌های نوروماژولاتوری مانند تحریک مغناطیسی ترانس‌کرانیال تکرارشونده (rTMS) و تحریک عمقی مغز (DBS) هستند. علاوه بر این، شواهد فزاینده‌ای ارتباط استرس اوایل زندگی با مسیرهای نوروانفلاماتوری و اختلال در محور هیپوتالاموس-هیپوفیز-آدرنال (HPA) را در اختلال وسواس فکری-عملی نشان می‌دهد که اهداف درمانی جدیدی را مطرح می‌کند. اگرچه کارآزمایی‌های بالینی مقدماتی مواد سریع‌الاثر نوین در اختلال وسواس فکری-عملی امیدبخش هستند، اما نتایج متناقض بوده و شواهد اندکی در مورد دوزهای مکرر وجود دارد. این مرور روایتی، شواهد فعلی درباره درمان‌های سریع‌الاثر و نوروماژولاتوری برای اختلال وسواس فکری-عملی را با تمرکز ویژه بر سازوکارهای مرتبط با استرس مرور می‌کند و امکانات درمانی جدید و مسیرهایی برای پژوهش‌های آینده ارائه می‌دهد.