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An evaluation of existing treatment practices for depression shows that they do not represent effective ways of treating this disorder. For instance, there is no definitive epidemiological evidence that antidepressants would be beneficial as a depression treatment. Moreover, antidepressants can have many side effects. The so-called monoamine hypothesis – according to which depression is caused by a lack of serotonin or other neurotransmitters in the brain – is outdated. Psychotherapy is only marginally more effective than placebo treatments, and this difference is below cut-offs for clinical significance. As there are different subtypes and underlying causes of depression, the same treatment is not expected to work for every patient. Classifying depression into subtypes based on evolutionary psychiatry is a novel approach – so novel that the effectiveness of specific treatments for all different subtypes of depression has not yet been tested. This chapter summarizes current knowledge on possible subtype-specific treatments for depression. Grounded in an evolutionary psychoneuroimmunological framework, the chapter emphasizes the importance of identifying the triggers, functions, and biological pathways underlying each depressive episode. By aligning treatment strategies with individual etiology and pathogenesis, this approach aims to improve treatment outcomes, reduce chronicity, and move toward more precise and intelligent depression interventions.
Psilocybin therapy has recently emerged as a promising new treatment for depression and other mental health disorders. This chapter summarizes the most recent data on its safety and efficacy. The delivery of psilocybin therapy and its subjective effects are also presented. Furthermore, this chapter outlines our current understanding of psilocybin’s pharmacology and neurobiological effects. Other similar psychedelic substances with encouraging therapeutic potential are briefly presented.
Psychedelics hold promise for psychiatry, yet clinical translation remains premature. Addressing the challenges of psychedelics in psychiatry requires advances in mechanistic study, clinical implementation, regulatory governance and public discourse in parallel.
Psychiatric disorders are complex conditions involving multifactorial, nonlinear causal dynamics, which make effective treatment challenging. To address this complexity, a framework is proposed that distinguishes between types of causality: permissive causality, which pertains to factors affecting the likelihood of an outcome occurring, and instructive causality, which refers to factors shaping the specific features of the outcome. In this framework, when considering an individual as a complex adaptive system, causal processes within the individual are permissive, whereas causal processes outside the individual can be either permissive or instructive in relation to the individual’s global emergent outcomes. Accordingly, when dealing with mental states or complex behaviors, biological substrates – from genes to brain areas – operate through permissive causality, shaping a space of possibilities rather than instructing a specific outcome. By contrast, contextual factors – such as life challenges or subjective appraisal – can also operate through instructive causality, steering behavior and mental states toward specific trajectories. Therapeutic strategies should harness the synergistic interplay between these types of causality, targeting biological substrates to enable transitions in mental states, and leveraging contextual factors to steer these transitions toward mental well-being. Recognizing such interplay holds promise for developing innovative and effective approaches in precision psychiatry, especially for treatments enhancing plasticity – which itself operates through permissive causality – including antidepressants and psychedelics.
This chapter traces William Burroughs’ encounters with yagé (ayahuasca) as a critical inflection point in his literary development and spiritual imagination. Marcus Boon explores the 1950s Amazonian journeys that led to The Yage Letters (1963) and its expanded edition The Yage Letters Redux (2006), arguing that Burroughs’ experiences with the vine laid the groundwork for his later explorations of language as virus, the cut-up method, and his cosmological vision of control and resistance. Intertwining Cold War paranoia, psychedelic experimentation, and postcolonial critique, Boon situates yagé not as an outlier in Burroughs’ oeuvre but as a key to understanding its epistemological and aesthetic radicalism. The chapter maps Burroughs’ legacy in the broader literary and anthropological discourse on ayahuasca, showing how his early visions resonate with – and complicate – contemporary movements for psychedelic healing, spiritual tourism, and decolonial thought. Burroughs, Boon suggests, helped carry yagé out of the jungle and into a globalized discourse of language, healing, and power.
I examine more closely the question of whether and how we can voluntarily access and benefit from accessing group mind content. I argue that some of the experiences on serotonergic psychedelics can be seen in terms of unstructured access to a variety of group minds. The ego dissolution experience on psychedelics can be viwed in terms of fusion between the individual and some salient group mind.
Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa.
Aims
This study aimed to further assess the safety, feasibility and potential efficacy of psilocybin therapy in anorexia nervosa.
Method
This single-blind, within-individual pilot study recruited 21 females with anorexia nervosa, who underwent three dosing sessions with oral psilocybin (COMP360) over 6 weeks in a fixed order (1 mg, 25 mg, 25 mg), alongside talk therapy and adjunctive to treatment as usual. Adverse events were monitored throughout the study. Primary clinical outcome measures were global Eating Disorder Examination Interview (EDE) and Readiness and Motivation Questionnaire (RMQ) precontemplation scores. Primary time points for the EDE were the 6-week final visit, 3-month follow-up and 6-month follow-up; and for the RMQ, they were the 6-week final visit and comparison between dosing days. Global EDE Questionnaire scores were a key secondary outcome. Key time points were the 6-week final visit and comparison between dosing days. There was a 12-month remote follow-up.
Results
Psilocybin was well tolerated by all participants. The most common adverse events were headache, nausea and dizziness. Two serious adverse events (suicide attempts) were reported for one participant within the 6–12-month period. Relative to baseline, participants displayed significant improvements in their eating disorder symptoms (EDE scores: p < 0.0001, d = 0.98, 6 months) and motivation to change (RMQ scores: p = 0.0017, d = 0.65, 12 months). However, there was a large variation in improvement and maintenance during the follow-up.
Conclusions
This study further provides preliminary support for the feasibility, safety and potential efficacy of this intervention to treat adult females with anorexia nervosa, and warrants further investigation in larger and more rigorously designed studies.
Psychedelics have led neuroscientists and policymakers to employ lexicons of theology and spirituality, but scholars of religion have been strikingly absent from the conversation. Consequently, psychedelic studies draws uncritically upon classic essentializations of “religious experience” that academic religious studies abandoned decades ago for crucial phenomenological and ethical reasons. In particular, psychedelic research would benefit from paying more attention to the hermeneutical dimensions of altered states, which point beyond perennialist paradigms. This article presents a case study of neo-Hasidism (non-Hasidic Jews who draw upon Hasidism for spiritual-cultural renewal). Representations of psychedelics in neo-Hasidism reveal not only a great deal about the movement itself, but also about the interpretive interplay between psychedelic experiences and situated subjectivities. Drawing upon neo-Hasidic discourses from the mid-1950s through early-1970s, including unpublished archival materials, this article investigates how Hasidic sources impact interpretations of psychedelic experiences and also, in turn, how those experiences transform perceptions of Hasidism.
Psychedelics were used for centuries in healing and spiritual rituals, long before the mid-20th century when they became subjects of biomedical research. Although initial trials generated optimism, these were quickly overshadowed by sensationalist media coverage and political backlash. Following decades of inactivity, research on compounds including 3,4-methylenedioxymethamphetamine (MDMA) has resurged, along with the media attention. Investigating this growing interest, Bender et al employed a large-language model, validated against human raters, to analyse 25 years of media articles (2000–2025), quantifying trends in sentiment towards psychedelic therapies. Findings showed a dramatic increase in coverage, with positive sentiment peaking in 2020 followed by a significant decline from 2024, coinciding with the U.S. Food and Drug Administration’s decision not to approve MDMA-assisted therapy for post-traumatic stress disorder, and echoing the dynamics of the 1960s. The authors emphasise that sustained progress in the field will require reliance on scientific evidence to advance therapeutic applications.
It is hard to overstate the importance of William Blake (1757–1827) within Allen Ginsberg’s life and poetry. The numinous event that Ginsberg experienced in 1948, which he would later call his “Blake vision,” became a key part of his self-fashioning as a countercultural visionary, a prophet in a tradition that stretched back through Blake to Milton and the Bible. As an expert salesman, Ginsberg also became a dedicated proselytizer for Blake, whose work he promoted not only through poetry but also college classes, interviews, music, and his vast personal network. Ginsberg thereby positioned Blake as a lodestar of the counterculture and ultimately influenced Blake’s position within popular culture and academia itself. However, Ginsberg’s narrative of his “Blake vision” also changed significantly over time, and Ginsberg’s strong link to Blake has sometimes obscured the importance to Ginsberg’s work of other Romantics, such as William Wordsworth.
Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, for example, in the frontal cortex, parts of the limbic system, including the amygdala and hippocampus, and striatum. The present study was conducted to shed further light on psilocybin-induced changes in gene expression.
Method:
Samples from the medial prefrontal cortex, cingulate cortex, hippocampus, amygdala, and striatum were collected from 24 male Wistar rats 90 min after they had been injected with either saline or psilocybin (2 mg/kg) and subjected to multi-region transcriptional profiling using 3prime-RNASeq technology.
Results:
Nfkbia and Sgk1 were upregulated in all the studied regions, Ddit4 was upregulated in four regions, and Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 were differentially expressed in two regions. Other cases of differentially expressed genes were region-specific.
Conclusion:
Whereas psilocybin was not found to alter the expression of genes encoding enzymes, transporters, or receptors implicated in the serotonergic signalling, or those specifically involved in the regulation of the synaptic activity of other neurotransmitters, a common denominator for many of the genes impacted by psilocybin is that they have previously been found to be activated by glucocorticoids.
While clinical research on psychedelics often reports mild and transient side effects, broader survey studies indicate that a subset of users experiences lasting adverse mental health effects. This study investigated whether some of these meet diagnostic criteria for post-traumatic stress disorder (PTSD).
Methods
A cross-sectional online survey (N = 243) was conducted with individuals reporting distressing psychedelic experiences with effects persisting beyond the acute phase (convenience sampling). It assessed characteristics of the acute experience, post-traumatic stress, post-traumatic growth, and coping strategies.
Results
A total of 31.3% of participants met the DSM-5 criteria for PTSD as measured by self-report measures. PTSD symptom severity was strongly associated with characteristics of the acute experience. Avoidance-related experiences significantly predicted greater PTSD symptoms, while acceptance-related experiences were linked to lower symptom severity. Post-traumatic growth was unrelated to the intensity of the challenging experience or avoidance but positively predicted by acceptance-related experiences. Post-psychedelic help-seeking behavior was common: most consulted online resources or spoke with friends and family, though psychotherapy was rated the most helpful intervention.
Discussion
Findings provide the first systematic evidence that difficult psychedelic experiences can be associated with later PTSD symptoms and highlight the critical role of acute psychological processes in shaping long-term outcomes. Since the survey targeted individuals with highly challenging acute experiences, the data do not allow the extrapolation of prevalence estimates to the broader population of psychedelic users. As psychedelic use expands beyond clinical settings, access to trauma-informed care and targeted integration support will be essential to minimize harm and support recovery.
The ’Introduction’ lays the intellectual foundation for the book by situating mind-altering substances within the broader arc of human cultural, neurological, and technological evolution. It argues that altered states of consciousness — whether chemically, behaviourally, or digitally induced — are not peripheral but central to the human experience. The chapter outlines how the search for transcendence, novelty, and meaning has driven innovations in medicine, ritual, and technology across millennia. It introduces the concept of ’experiential adaptation’ to describe how societies continually modify consciousness in response to environmental, social, and symbolic pressures. The introduction also maps out the interdisciplinary methodology of the book, drawing from anthropology, neuroscience, history, digital media studies, and future forecasting. It prepares the reader to navigate a narrative that stretches from Palaeolithic natural and artificial, healthy and pathological, sacred and simulated.
Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials.
Methods
A systematic search was conducted up to 1 July 2025. The study protocol was preregistered in PROSPERO (CRD420251111853).
Results
Fourteen randomized controlled trials (n = 643) were included. Direct between-arm meta-analyses showed greater symptom reductions in treatment compared with control across outcomes, including depressive symptoms (number of study arms [k] = 13; SMD = −0.82; 95% CI = −1.17, −0.47; I2 = 60.1%), posttraumatic stress disorder (PTSD) symptoms (k = 10; SMD = −0.89; 95% CI = −1.14, −0.65; I2 = 0%), and anxiety symptoms (k = 5; SMD = −0.66; 95% CI = −0.94, −0.38; I2 = 0%). Subgroup analyses showed limited evidence that effects differed by placebo type for depressive or PTSD symptoms. Descriptive within-group analyses indicated symptom reductions from baseline in both control and treatment groups, with larger within-group improvements observed in treatment groups across outcomes; notably, larger within-group reductions in PTSD symptoms were observed in inactive placebo groups. Sensitivity analyses showed consistent results.
Conclusions
Control groups in psychedelic trials demonstrated substantial symptom improvement, which may reflect non-specific trial factors (including expectancy and concurrent psychotherapy). These findings emphasize the importance of robust control conditions in psychedelic research and the need for nuanced interpretation of treatment effects.
Mysticism refers to extraordinary experiences that transcend perceived reality and transform the individual. Section 1 introduces key features such as noetic and ineffable qualities, alongside psychological typologies and a fourfold hierarchy of mystical forms. Section 2 explores monistic mysticism, where self and ultimate reality merge in oneness and ego-dissolution, illustrated through perennial philosophy and its critiques. Section 3 examines nondualistic mysticism, in which the self remains distinct yet is absorbed into a transcendent order, exemplified in world religions where ego yields to the divine. Section 4 discusses dualistic mysticism, where the self encounters a separate nonhuman reality, often expressed through shamanism, spiritist visions, and psychedelic states. Section 5 presents pluralistic mysticism, emphasizing multiple dimensions of self and reality, integrating embodied and spiritual aspects, and drawing on nonphysicalism and parapsychology. Section 6 synthesizes these perspectives, stressing that transcendent realities require self-transformation and that mystical insights can inform daily life across culture.
Serendipity has driven many of psychiatry’s most important treatments, yet contemporary systems may undermine clinicians’ ability to notice and develop unexpected therapeutic effects. This selective narrative review synthesises landmark discovery stories, conceptual accounts of serendipity and contemporary case examples to clarify how chance observations become robust advances.
Results
Across historical and modern examples, serendipitous discoveries consistently reflected the interaction of unexpected events with prepared observers working in supportive institutional and research systems. We identify current barriers created by standardised care, funding and trial structures, and professional fragmentation, and outline a multi-level framework for cultivating serendipity through phenomenological training, technology-enabled detection of anomalous responses, flexible funding and innovative designs such as adaptive platform and rapid-fail proof-of-concept trials.
Clinical implications
Deliberately creating pathways that move rare, surprising responses from bedside observation to formal evaluation could accelerate more precise, personalised treatments while preserving rigor in psychiatric care.
Interest in psilocybin as a treatment for depression has risen over the past decade, fuelled by promising clinical trials and a rapidly evolving regulatory landscape. Media coverage plays a critical role in shaping public perceptions, yet little is known about how psilocybin is portrayed in global anglophone online news for the treatment of depression.
Methods:
This study examines the comprehensiveness and sentiment of English-language online news articles (n = 125) discussing psilocybin as a treatment for depression from January 2000 to May 2024. Articles were sourced from the top 30 global anglophone news outlets, assessed using a 13-item instrument for comprehensiveness, and analysed for sentiment across five thematic categories. A separate sub-analysis was completed for Irish media.
Results:
Findings indicate a significant increase in coverage over time, with 43.2% of articles published between 2022 and 2024, predominantly from the USA (68%). While 90.4% of articles cited researchers, fewer addressed risks (47.2%), long-term evidence (46.4%), or patient perspectives (25%). Sentiment analysis revealed a very positive sentiment across articles which was 2.27 on a scale from −5 (most negative) to + 5 (most positive) (SD 1.33), with no significant changes over the time period. Reporting on psilocybin’s onset and duration of effects increased significantly, reflecting growing clinical evidence. However, coverage remains concentrated in prominent outlets, with limited attention to patient experiences and long-term safety.
Conclusions:
These findings highlight the media’s role in shaping discourse on emerging treatments and suggest a need for more balanced reporting to align public understanding with scientific evidence. This study provides a foundation for future research on media portrayals of psilocybin and implications for public perception and policy.
Psychedelic medicines hold the promise of therapeutic benefit for many suffering from serious unmet mental health needs, leading to substantial demand even before these drugs receive FDA approval based on demonstrated safety and effectiveness for particular conditions. Recognizing FDA approval as the ideal path for psychedelics intended for medical use and drawing on lessons from medical marijuana, we encourage policymakers to balance the need for evidence, the importance of patient safeguards, and the desire for speed. They should increase support for psychedelic research, reject approaches that could inhibit that research, explore improvements to FDA’s existing pre-approval access pathway, and avoid politically motivated FDA approval of psychedelic medicines.
Howard CH Khoe, National Psychiatry Residency Programme, Singapore,Cheryl WL Chang, National University Hospital, Singapore,Cyrus SH Ho, National University Hospital, Singapore
Chapter 29 covers the topic of hallucinogen use disorder. Through a case vignette with topical MCQs for consolidation of learning, readers go through the management of a patient with hallucinogen use disorder from from first presentation to subsequent complications of the condition and its treatment. Topics covered include symptoms and diagnosis of acute intoxication and withdrawal symptoms of phencylidine and hallucinogen-persisting perception disorder.
This article traces the shifting fortunes of for-profit psychedelic medicine through two phases: a boom from 2016 to late 2021, followed by a bust that continued through late 2024. It argues that the forces driving this cycle are best understood through the concept of capitalization, which links present valuations to investor expectations about future earnings. Engaging the capital-as-power framework, the article situates psychedelic companies within the broader biopharmaceutical sector, showing how the volatility of drug development is intensified by the unruliness of these substances as capitalized assets. This unruliness stems from a range of factors, including murky intellectual property claims, unpredictable and intense subjective experiences, and lingering cultural stigma. During the boom, firms attracted significant interest from venture capital and other investors by promising revolutionary breakthroughs in mental health treatment. As expectations rose, so did valuations. But disappointing results from clinical trials, regulatory setbacks, and deepening doubts about the ability to control and standardize psychedelic therapies led to sharp declines in investor confidence. Analyzing financial performance alongside investor narratives, the article underscores the tensions involved in subjecting these unruly substances to the logic of capitalist power.